Director's Blog
A Successful and Memorable NF Family Day and Plans for Future Dermal Neurofibroma Trials
By: Bruce Korf
Published Date: Sep 23
The month of August neared an end with yet another successful and memorable Neurofibromatosis Symposium held at the UAB Hugh Kaul Genetics Building on August 29th. Also known as NF Family Day, this half-day, free event co-sponsored by UAB and the Children’s Tumor Foundation (CTF) provided NF patients and their families with valuable information through a series of presentations given by clinical experts on a range of NF-related topics. We were especially pleased to have 100 people registered for the Symposium, which marks the largest attendance for the event to date. A unique highlight of NF Family Day this year was a special program designed for the children in attendance, provided by our genetic counseling students, that included special materials donated by the Homewood Library as well as an exciting and memorable visit by members of the Birmingham Fire Department replete with an authentic fire truck the children could tour during our lunch break.
To begin the Symposium, I gave an overview of neurofibromatosis including information about each of the three types of NF, a general summary of current research findings, and the role of genetic testing. Some families in attendance may have heard this information previously while for others, especially those facing a new diagnosis, it may have been new. Alyssa Reddy, MD, director of the Children’s Hospital of Alabama Neuro-Oncology Program, explained UAB’s dual role as both the national coordinating center for the NF Clinical Trials Consortium and one of the national patient recruitment sites for clinical trials. She also provided an overview of her efforts in recruiting patients for NF-related clinical trials and explained enrollment criteria and the informed consent process. In addition, Dr. Reddy discussed some of the latest treatment options for specific NF tumor types, such as optic gliomas and plexiform neurofibromas. Continuing with information about the NF Program’s robust research initiatives, graduate student Ashley Turner, MS, summarized her work in the NF laboratory developing mouse models with human NF mutations in order to test compounds that might prove effective in treating tumors; this research serves an important foundational step in the drug discovery process by helping to identify potential drugs that could be tested in future human clinical trials.
Our new NF Program genetics counselor Ashley Cannon, PhD, MS, CGC, presented information about NF-related learning disabilities and explained the process of navigating the often complex terrain of establishing IEP and 504 plans for school-aged children. Dr. Cannon stressed to parents that while NF-related learning disabilities and difficulties most often become evident in school-aged children, learning challenges do not go away as children move into adolescence and adulthood; instead, people with NF can struggle with learning difficulties throughout their lives, particularly if they do not receive appropriate educational services during early childhood.
Also, Dr. Cannon provided information about the NF registry (https://nfregistry.patientcrossroads.org) established by CTF in 2012 and provided attendees the opportunity to join while at the Symposium; the purpose of the NF Registry is to help notify NF patients who may be eligible for clinical trials or other research studies and to determine the frequency of specific NF characteristics. Next, UAB Associate Professor of Anesthesiology and pain expert James Weisberg, PhD, discussed pain management for NF patients, emphasizing the need to utilize a holistic approach in treating pain that incorporates medication with cognitive-behavioral therapies.
To close the program, well-known patient advocate and Birmingham parent of two children with NF, Renie Moss, presented information on patient advocacy while Kristen Stanley from CTF spoke about the work of the organization and upcoming events. The annual NF Symposium, in addition to providing patients and families with an important forum about NF-related topics, also serves to help NF families establish supportive connections with others facing similar challenges and concerns. We find it rewarding to have the opportunity to facilitate these two meaningful purposes through this event.
As I mentioned in a previous post, I often receive questions from patients asking why clinical trials focus on plexiform neurofibromas, while there are no clinical trials in progress for dermal neurofibromas. Part of the reason is that the complications of plexiforms are often more medically serious than for dermal neurofibromas and can sometimes be life-threatening. However, some good news to share is that our program recently submitted a grant proposal for a dermal neurofibroma clinical trial; although it will be a while until we know if we will receive funding, our program is committed to actively pursuing clinical trials of dermal neurofibromas.
To begin the Symposium, I gave an overview of neurofibromatosis including information about each of the three types of NF, a general summary of current research findings, and the role of genetic testing. Some families in attendance may have heard this information previously while for others, especially those facing a new diagnosis, it may have been new. Alyssa Reddy, MD, director of the Children’s Hospital of Alabama Neuro-Oncology Program, explained UAB’s dual role as both the national coordinating center for the NF Clinical Trials Consortium and one of the national patient recruitment sites for clinical trials. She also provided an overview of her efforts in recruiting patients for NF-related clinical trials and explained enrollment criteria and the informed consent process. In addition, Dr. Reddy discussed some of the latest treatment options for specific NF tumor types, such as optic gliomas and plexiform neurofibromas. Continuing with information about the NF Program’s robust research initiatives, graduate student Ashley Turner, MS, summarized her work in the NF laboratory developing mouse models with human NF mutations in order to test compounds that might prove effective in treating tumors; this research serves an important foundational step in the drug discovery process by helping to identify potential drugs that could be tested in future human clinical trials.
Our new NF Program genetics counselor Ashley Cannon, PhD, MS, CGC, presented information about NF-related learning disabilities and explained the process of navigating the often complex terrain of establishing IEP and 504 plans for school-aged children. Dr. Cannon stressed to parents that while NF-related learning disabilities and difficulties most often become evident in school-aged children, learning challenges do not go away as children move into adolescence and adulthood; instead, people with NF can struggle with learning difficulties throughout their lives, particularly if they do not receive appropriate educational services during early childhood.
Also, Dr. Cannon provided information about the NF registry (https://nfregistry.patientcrossroads.org) established by CTF in 2012 and provided attendees the opportunity to join while at the Symposium; the purpose of the NF Registry is to help notify NF patients who may be eligible for clinical trials or other research studies and to determine the frequency of specific NF characteristics. Next, UAB Associate Professor of Anesthesiology and pain expert James Weisberg, PhD, discussed pain management for NF patients, emphasizing the need to utilize a holistic approach in treating pain that incorporates medication with cognitive-behavioral therapies.
To close the program, well-known patient advocate and Birmingham parent of two children with NF, Renie Moss, presented information on patient advocacy while Kristen Stanley from CTF spoke about the work of the organization and upcoming events. The annual NF Symposium, in addition to providing patients and families with an important forum about NF-related topics, also serves to help NF families establish supportive connections with others facing similar challenges and concerns. We find it rewarding to have the opportunity to facilitate these two meaningful purposes through this event.
As I mentioned in a previous post, I often receive questions from patients asking why clinical trials focus on plexiform neurofibromas, while there are no clinical trials in progress for dermal neurofibromas. Part of the reason is that the complications of plexiforms are often more medically serious than for dermal neurofibromas and can sometimes be life-threatening. However, some good news to share is that our program recently submitted a grant proposal for a dermal neurofibroma clinical trial; although it will be a while until we know if we will receive funding, our program is committed to actively pursuing clinical trials of dermal neurofibromas.
A New Specialist Joins the NF Clinic Team, Upcoming NF Symposium at UAB, and Understanding RAS Disorders and their Relationship to NF
By: Bruce Korf
Published Date: Aug 03
As I mentioned in the previous blog, we are pleased to announce the addition of Dr. Ashley Cannon, a genetic counselor and clinical researcher, to our team of specialists in the UAB NF Clinic. With a unique and diverse background that includes a Ph.D. in neuroscience and a degree in genetic counseling (completed at UAB), Dr. Cannon brings a range of capabilities that will further enhance both patient care and clinical research. She will play an integral role in seeing patients in the clinic, helping to identify the needs of individual patients, organizing genetic testing, and providing genetic counseling. In addition, Dr. Cannon will serve a key role in coordinating clinical trials and research studies conducted in the NF research program. I have also asked her to begin the process of establishing our community advisory board, which will be comprised of NF patients and family members who will provide valuable feedback to ensure the NF Clinic is functioning in a way that best meets their needs.
Currently, Dr. Cannon is assisting with final preparations for the upcoming Neurofibromatosis Symposium to be held at the Finley Conference Center in the Kaul Human Genetics Building on Saturday, August 29th. Co-sponsored by UAB and the Children’s Tumor Foundation (CTF), this half-day, free event is designed to provide NF patients and their families with information about a range of NF-related topics including: an overview of neurofibromatosis; updates on clinical trials and other research advances; genetic counseling and the NF registry; pain management; a patient and family roundtable discussion; advocacy, fundraising, and upcoming events in the NF community; and a question-and-answer session. Breakfast, lunch, and childcare will be provided for the convenience of our families. While there is no cost to attend, reservations should be made by August 24th by emailing acannon@uab.edu. This is an invaluable opportunity for NF patients and families – especially those facing a new diagnosis – to gain information, support, and answers to questions about neurofibromatosis. Each year, we look forward to serving NF patients and their families through this important forum that not only provides key information about NF but also offers the opportunity for NF families to gain understanding and strength through sharing their experiences, challenges, and concerns.
Neurofibromatosis Symposium: Family Day 2015
Saturday, August 29th, 2015
Schedule:
08:00-08:30am Register/Breakfast
08:30-10:00am Welcome/NF 101/Updates – Dr. Bruce Korf
10:00-10:30am Break
10:30-11:00am Clinical Trials Update – Dr. Alyssa Reddy
11:00-11:30am Research Studies – Ashley Turner
11:30-12:00pm Counseling Issues/Registry – Ashley Cannon
12:00-12:30pm Pain Management – Dr. James Weisberg
12:30-01:30pm Lunch / Patient and Family Roundtable
01:30-02:00pm Advocacy, Fundraising, Upcoming Events – Renie Moss
On July 17th- 19th, I attended the 4th International RASopathies Symposium in Seattle, Washington. The RASopathies are a group of medical genetic syndromes, including NF1, that have in common the fact that their underlying genetic alterations occur in a critical cellular signaling pathway called the RAS/MAPK pathway. Neurofibromatosis type 1 is caused by a genetic alteration in the gene that encodes for neurofibromin, a protein regulating activity of the RAS signaling pathway that also has a role in cell growth and division. As in NF1, the RAS pathway can be disturbed in a host of other syndromes including Noonan syndrome, cardiofaciocutaneous (CFC) syndrome, Legius syndrome, and Costello syndrome. All RASopathy syndromes affect multiple systems of the body; features such as cardiac disease, growth deficits, facial characteristics, bone and skin abnormalities, and learning and behavior problems are common. However, as with NF1, the presence and severity of these features varies widely among affected individuals.
The purpose of the RASopathies Symposium is to bring together scientists, clinicians, researchers, and affected families to facilitate a collaborative discussion focused on future research, development of therapies, and best clinical practices for RAS/MAPK pathway syndromes. Because NF1 was the first RASopathy to be identified, we in the NF scientific community are much further along than the other related syndromes in our capability to develop clinical trials focused on mechanism-based therapies. This is due in part to the fact that we’ve known about NF1 for a longer period of time and also because it is easier to define what success would look like in an NF patient. It is encouraging that the development of mechanism-based therapies that inhibit the over-activated RAS pathway and other RAS-connected pathways opens new avenues of therapeutic intervention for the many complications of the RAS disorders. Because neurofibromatosis has been a beacon in the realm of mechanism-based therapeutics, other RAS disorders are looking to the NF scientific community for examples in the development of effective treatments; we’re certainly hopeful that we can share valuable information based on our experience with NF and that this shared knowledge will facilitate research that will benefit those with the various RAS disorders.
Currently, Dr. Cannon is assisting with final preparations for the upcoming Neurofibromatosis Symposium to be held at the Finley Conference Center in the Kaul Human Genetics Building on Saturday, August 29th. Co-sponsored by UAB and the Children’s Tumor Foundation (CTF), this half-day, free event is designed to provide NF patients and their families with information about a range of NF-related topics including: an overview of neurofibromatosis; updates on clinical trials and other research advances; genetic counseling and the NF registry; pain management; a patient and family roundtable discussion; advocacy, fundraising, and upcoming events in the NF community; and a question-and-answer session. Breakfast, lunch, and childcare will be provided for the convenience of our families. While there is no cost to attend, reservations should be made by August 24th by emailing acannon@uab.edu. This is an invaluable opportunity for NF patients and families – especially those facing a new diagnosis – to gain information, support, and answers to questions about neurofibromatosis. Each year, we look forward to serving NF patients and their families through this important forum that not only provides key information about NF but also offers the opportunity for NF families to gain understanding and strength through sharing their experiences, challenges, and concerns.
Neurofibromatosis Symposium: Family Day 2015
Saturday, August 29th, 2015
Schedule:
08:00-08:30am Register/Breakfast
08:30-10:00am Welcome/NF 101/Updates – Dr. Bruce Korf
10:00-10:30am Break
10:30-11:00am Clinical Trials Update – Dr. Alyssa Reddy
11:00-11:30am Research Studies – Ashley Turner
11:30-12:00pm Counseling Issues/Registry – Ashley Cannon
12:00-12:30pm Pain Management – Dr. James Weisberg
12:30-01:30pm Lunch / Patient and Family Roundtable
01:30-02:00pm Advocacy, Fundraising, Upcoming Events – Renie Moss
On July 17th- 19th, I attended the 4th International RASopathies Symposium in Seattle, Washington. The RASopathies are a group of medical genetic syndromes, including NF1, that have in common the fact that their underlying genetic alterations occur in a critical cellular signaling pathway called the RAS/MAPK pathway. Neurofibromatosis type 1 is caused by a genetic alteration in the gene that encodes for neurofibromin, a protein regulating activity of the RAS signaling pathway that also has a role in cell growth and division. As in NF1, the RAS pathway can be disturbed in a host of other syndromes including Noonan syndrome, cardiofaciocutaneous (CFC) syndrome, Legius syndrome, and Costello syndrome. All RASopathy syndromes affect multiple systems of the body; features such as cardiac disease, growth deficits, facial characteristics, bone and skin abnormalities, and learning and behavior problems are common. However, as with NF1, the presence and severity of these features varies widely among affected individuals.
The purpose of the RASopathies Symposium is to bring together scientists, clinicians, researchers, and affected families to facilitate a collaborative discussion focused on future research, development of therapies, and best clinical practices for RAS/MAPK pathway syndromes. Because NF1 was the first RASopathy to be identified, we in the NF scientific community are much further along than the other related syndromes in our capability to develop clinical trials focused on mechanism-based therapies. This is due in part to the fact that we’ve known about NF1 for a longer period of time and also because it is easier to define what success would look like in an NF patient. It is encouraging that the development of mechanism-based therapies that inhibit the over-activated RAS pathway and other RAS-connected pathways opens new avenues of therapeutic intervention for the many complications of the RAS disorders. Because neurofibromatosis has been a beacon in the realm of mechanism-based therapeutics, other RAS disorders are looking to the NF scientific community for examples in the development of effective treatments; we’re certainly hopeful that we can share valuable information based on our experience with NF and that this shared knowledge will facilitate research that will benefit those with the various RAS disorders.
Understanding Possible Explanations for Isolated Features of NF
By: Bruce Korf
Published Date: Jul 08
Frequently I receive questions, through both e-mails and individuals who are referred to my office, regarding patients who have one isolated feature of NF but do not have a confirmed diagnosis of neurofibromatosis. These isolated features most often occur in the form of either plexiform neurofibromas or optic gliomas, although they sometimes may include dermal neurofibromas or bone dysplasia. It is important to know that isolated features of NF can occasionally been seen in both children and adults who do not actually have the condition. I’d like to give a brief overview of how we evaluate patients with only one isolated feature of NF in the absence of other symptoms and provide some possible explanations of why this phenomenon may occur.
Some individuals develop plexiform neurofibromas – tumors that involve multiple branches of large nerves – in one isolated area of the body, such as the spine, with no other features of NF. The age of presentation varies, but it usually begins from the teenage years into adulthood, as the symptoms of a plexiform neurofibroma do not become apparent until adolescence. Isolated optic gliomas, tumors of the optic nerve, can also occur in children and adults who have no other features of NF. Unlike isolated plexiform neurofibromas, optic gliomas that occur in individuals who do not have NF are typically more aggressive tumors than those found in people who have neurofibromatosis. Some individuals also develop isolated dermal neurofibromas or bone dysplasia in the absence of other NF features and with no confirmed diagnosis of neurofibromatosis.
When we see someone in our clinic with an isolated feature of NF, we provide a comprehensive evaluation to make certain that subtle features of the condition are not present. In some cases, if possible, we obtain a tissue sample of the tumor, although this is often difficult due to the location of tumors, such as plexiform neurofibromas deep inside the body. Sometimes we obtain a blood sample for genetic testing; however, a negative result does not necessarily confirm that an individual does not have NF.
There are at least three possible explanations for the occurrence of isolated NF features in some individuals. The first is mosaicism, caused by a mutation in the NF1 gene that occurs early in embryonic development and that only affects certain cells in the body. As a result, individuals with mosaicism have features of NF1 that are limited to only one part of their body, such as neurofibromas or café-au-lait spots in a certain region. The only method of confirming mosaicism is to biopsy the lesion and do genetic testing on the tissue. A second possible explanation for the occurrence of isolated features of NF is that there could be other, still unknown mechanisms that cause tumors that occur in people with NF to also occur in individuals who do not have the condition.
A third possible explanation is related to the specific “two-hit” genetic mechanism that causes the development of tumors in people with NF1. All persons have two copies of the gene, one inherited from each parent. In individuals with NF1, one copy of the NF1 gene is altered, or mutated, due to either inheriting the mutated gene from a parent, a new mutation that occurs in the egg or sperm prior to conception, or from a mutation that occurs early in embryonic development. This represents the “first-hit” genetic mutation. For a neurofibroma to develop in someone with NF1, a random genetic mutation must occur to the other copy of the NF1 gene in the tissue that will become the neurofibroma, café-au-lait spot, or other lesion; this is referred to as the “second-hit” mutation. Although an extremely rare occurrence, it is also possible for some individuals to acquire two random NF mutations, affecting each inherited copy of the NF1 gene, in a cell that could become a neurofibroma or other lesion. This two-hit mutation – similar to lightning striking twice in the same place – could result in the development of an isolated feature of NF in the absence of other signs of the condition.
On another topic, there are two things to report regarding the UAB NF Program. First, Dr. Ashley Cannon has joined the program as genetic counselor and clinical research coordinator. Dr. Cannon has unique training both as a neuroscientist and genetic counselor; she will be seeing patients with me in clinic and also involved in many of our research studies and clinical trials. Second, we will be hosting our annual NF Symposium this summer on Saturday, August 29. As in the past, the focus will be on educating patients and families about NF and highlighting research progress. We have assembled a group of speakers both from UAB and from the Children’s Tumor Foundation who will participate. If interested in knowing more about the symposium please contact Dr. Cannon at acannon@uab.edu. We look forward to seeing as many families as possible at this event!
Some individuals develop plexiform neurofibromas – tumors that involve multiple branches of large nerves – in one isolated area of the body, such as the spine, with no other features of NF. The age of presentation varies, but it usually begins from the teenage years into adulthood, as the symptoms of a plexiform neurofibroma do not become apparent until adolescence. Isolated optic gliomas, tumors of the optic nerve, can also occur in children and adults who have no other features of NF. Unlike isolated plexiform neurofibromas, optic gliomas that occur in individuals who do not have NF are typically more aggressive tumors than those found in people who have neurofibromatosis. Some individuals also develop isolated dermal neurofibromas or bone dysplasia in the absence of other NF features and with no confirmed diagnosis of neurofibromatosis.
When we see someone in our clinic with an isolated feature of NF, we provide a comprehensive evaluation to make certain that subtle features of the condition are not present. In some cases, if possible, we obtain a tissue sample of the tumor, although this is often difficult due to the location of tumors, such as plexiform neurofibromas deep inside the body. Sometimes we obtain a blood sample for genetic testing; however, a negative result does not necessarily confirm that an individual does not have NF.
There are at least three possible explanations for the occurrence of isolated NF features in some individuals. The first is mosaicism, caused by a mutation in the NF1 gene that occurs early in embryonic development and that only affects certain cells in the body. As a result, individuals with mosaicism have features of NF1 that are limited to only one part of their body, such as neurofibromas or café-au-lait spots in a certain region. The only method of confirming mosaicism is to biopsy the lesion and do genetic testing on the tissue. A second possible explanation for the occurrence of isolated features of NF is that there could be other, still unknown mechanisms that cause tumors that occur in people with NF to also occur in individuals who do not have the condition.
A third possible explanation is related to the specific “two-hit” genetic mechanism that causes the development of tumors in people with NF1. All persons have two copies of the gene, one inherited from each parent. In individuals with NF1, one copy of the NF1 gene is altered, or mutated, due to either inheriting the mutated gene from a parent, a new mutation that occurs in the egg or sperm prior to conception, or from a mutation that occurs early in embryonic development. This represents the “first-hit” genetic mutation. For a neurofibroma to develop in someone with NF1, a random genetic mutation must occur to the other copy of the NF1 gene in the tissue that will become the neurofibroma, café-au-lait spot, or other lesion; this is referred to as the “second-hit” mutation. Although an extremely rare occurrence, it is also possible for some individuals to acquire two random NF mutations, affecting each inherited copy of the NF1 gene, in a cell that could become a neurofibroma or other lesion. This two-hit mutation – similar to lightning striking twice in the same place – could result in the development of an isolated feature of NF in the absence of other signs of the condition.
On another topic, there are two things to report regarding the UAB NF Program. First, Dr. Ashley Cannon has joined the program as genetic counselor and clinical research coordinator. Dr. Cannon has unique training both as a neuroscientist and genetic counselor; she will be seeing patients with me in clinic and also involved in many of our research studies and clinical trials. Second, we will be hosting our annual NF Symposium this summer on Saturday, August 29. As in the past, the focus will be on educating patients and families about NF and highlighting research progress. We have assembled a group of speakers both from UAB and from the Children’s Tumor Foundation who will participate. If interested in knowing more about the symposium please contact Dr. Cannon at acannon@uab.edu. We look forward to seeing as many families as possible at this event!
Responding to E-mailed Questions from Patients and Reviewing Diagnostic Criteria for Café-Au-Lait Spots and Groin Freckling
By: Bruce Korf
Published Date: May 07
On an almost daily basis, I receive e-mails from people in all parts of the U.S. and other countries asking clinical questions about NF. Most of the time, individuals who e-mail me have run across my name on social networking sites, such as a discussion board or a chat room devoted to the topic of NF. There is a robust network of NF-related discussion forums on the Internet, and they can serve as a valuable resource for patients and families in locating specialists who can provide a definitive diagnosis and treatment plan. In this blog, I’d like to address the general principles I follow in replying to patients’ questions via e-mail.
Because most of the people who contact me have questions about clinical features that might indicate NF – or they have already received a diagnosis and need a plan of treatment – my primary goal is to connect them with a qualified specialist in their area whenever possible, and I always stress in my response the importance of identifying a trusted clinician in the region. Fortunately, specialists can be found relatively easily in most major U.S. cities. For patients and families seeking assistance in locating a specialist, the Children’s Tumor Foundation (www.ctf.org) web site features a patient information tab that provides a list of specialists within the U.S.
However, finding a qualified NF specialist often can be challenging, especially for people in other countries. In many regions of the U.S., and in many other countries, there is not ready access to NF specialists, and some physicians with the clinical knowledge to make an NF diagnosis may lack experience in managing complications and developing a treatment plan. For these reasons, NF-related discussion boards and chat rooms have proven to be a valuable resource for patients and families seeking information and guidance.
Because I understand the importance of helping people gain access to accurate information about NF, I’m always glad to respond to any e-mailed questions I receive and consider it a privilege to communicate with patients who have NF-related concerns. However, I can’t provide specific medical advice to people whom I have not personally examined and whose records I have not reviewed. Many people who e-mail me often attach photos, for example of café-au-lait spots, usually taken with a cell phone. Most of these photos are difficult to interpret, and it’s important not to give advice based on the limited information provided in an e-mail or photo. Instead, I focus on providing general information about NF that is not specific to their situation – perhaps about the value of genetic testing or a review of different treatment approaches.
Regarding the numerous e-mailed questions I receive asking if a child with café-au-lait spots has NF, the majority describe children in whom a diagnosis of NF is not obvious. Parents of these children are usually distraught about the possibility of NF based on the presence café-au-lait spots, which may have been noticed by a pediatrician or other clinician. Frequently, I have the impression that most are healthy children with a few spots that don’t fulfill the diagnostic criteria requiring six or more café-au-lait spots. It is important to note that the vast majority of people with NF1 have this number of café-au-lait spots or more. Sometimes, infants can develop café-au-lait spots, but café-au-lait spots usually begin to appear in the first few weeks of life. By two years of age, a child with NF will have at least six café-au-lait spots, if they ever will. It’s important to note that a young child with six or more café-au-lait spots that are clear usually will have NF1 that can be confirmed with genetic testing. In my clinical experience, many children with between one and three spots usually don’t have NF.
There are some people with variant forms of NF who have fewer than six café-au-lait spots. Some of these individuals develop internal neurofibromas, but have few visible on the skin. Legius Syndrome is another condition that causes café-au-lait spots, although these individuals do not develop tumors; this is a benign condition that is much more rare than NF1, and genetic testing is required to confirm it. Also, there are other conditions that can produce café-au-lait spots, though most are rare. It should also be noted that some healthy people can have up to six spots with no other symptoms.
Freckling in the groin and under the arms is another feature used to confirm an NF1 diagnosis. While some parents may worry based on the presence of a few small freckles in these regions, it’s important to note that NF-related freckling appears between three and five years of age. Instead of a few tiny freckles in these regions, there are usually many freckles in the region, as if paint were spattered from a paint brush. Also, a café-au-lait spot that happens to appear under the arm or in the groin does not count as a skin fold freckle.
Because NF-related features such as café-au-lait spots and groin and underarm freckling are sometimes over-interpreted and often a source of unnecessary anxiety, it’s important to identify an experienced clinician who can make a recommendation about diagnosis and the use of genetic testing for NF based on the presence of specific clinical criteria. My continued objective in responding to e-mailed questions is to provide patients with accurate information about NF and assist them in identifying an experienced, trusted clinician who can provide additional information and guidance.
Because most of the people who contact me have questions about clinical features that might indicate NF – or they have already received a diagnosis and need a plan of treatment – my primary goal is to connect them with a qualified specialist in their area whenever possible, and I always stress in my response the importance of identifying a trusted clinician in the region. Fortunately, specialists can be found relatively easily in most major U.S. cities. For patients and families seeking assistance in locating a specialist, the Children’s Tumor Foundation (www.ctf.org) web site features a patient information tab that provides a list of specialists within the U.S.
However, finding a qualified NF specialist often can be challenging, especially for people in other countries. In many regions of the U.S., and in many other countries, there is not ready access to NF specialists, and some physicians with the clinical knowledge to make an NF diagnosis may lack experience in managing complications and developing a treatment plan. For these reasons, NF-related discussion boards and chat rooms have proven to be a valuable resource for patients and families seeking information and guidance.
Because I understand the importance of helping people gain access to accurate information about NF, I’m always glad to respond to any e-mailed questions I receive and consider it a privilege to communicate with patients who have NF-related concerns. However, I can’t provide specific medical advice to people whom I have not personally examined and whose records I have not reviewed. Many people who e-mail me often attach photos, for example of café-au-lait spots, usually taken with a cell phone. Most of these photos are difficult to interpret, and it’s important not to give advice based on the limited information provided in an e-mail or photo. Instead, I focus on providing general information about NF that is not specific to their situation – perhaps about the value of genetic testing or a review of different treatment approaches.
Regarding the numerous e-mailed questions I receive asking if a child with café-au-lait spots has NF, the majority describe children in whom a diagnosis of NF is not obvious. Parents of these children are usually distraught about the possibility of NF based on the presence café-au-lait spots, which may have been noticed by a pediatrician or other clinician. Frequently, I have the impression that most are healthy children with a few spots that don’t fulfill the diagnostic criteria requiring six or more café-au-lait spots. It is important to note that the vast majority of people with NF1 have this number of café-au-lait spots or more. Sometimes, infants can develop café-au-lait spots, but café-au-lait spots usually begin to appear in the first few weeks of life. By two years of age, a child with NF will have at least six café-au-lait spots, if they ever will. It’s important to note that a young child with six or more café-au-lait spots that are clear usually will have NF1 that can be confirmed with genetic testing. In my clinical experience, many children with between one and three spots usually don’t have NF.
There are some people with variant forms of NF who have fewer than six café-au-lait spots. Some of these individuals develop internal neurofibromas, but have few visible on the skin. Legius Syndrome is another condition that causes café-au-lait spots, although these individuals do not develop tumors; this is a benign condition that is much more rare than NF1, and genetic testing is required to confirm it. Also, there are other conditions that can produce café-au-lait spots, though most are rare. It should also be noted that some healthy people can have up to six spots with no other symptoms.
Freckling in the groin and under the arms is another feature used to confirm an NF1 diagnosis. While some parents may worry based on the presence of a few small freckles in these regions, it’s important to note that NF-related freckling appears between three and five years of age. Instead of a few tiny freckles in these regions, there are usually many freckles in the region, as if paint were spattered from a paint brush. Also, a café-au-lait spot that happens to appear under the arm or in the groin does not count as a skin fold freckle.
Because NF-related features such as café-au-lait spots and groin and underarm freckling are sometimes over-interpreted and often a source of unnecessary anxiety, it’s important to identify an experienced clinician who can make a recommendation about diagnosis and the use of genetic testing for NF based on the presence of specific clinical criteria. My continued objective in responding to e-mailed questions is to provide patients with accurate information about NF and assist them in identifying an experienced, trusted clinician who can provide additional information and guidance.
Measurement Technique for Dermal Neurofibromas Validated at UAB Expands Possibilities for Clinical Trials
By: Bruce Korf
Published Date: Apr 03
In continuing our discussion from the previous blog regarding how the focus of a clinical trial is determined, I’d like to address the treatment and research of two distinctive features of NF that are of significant concern to patients – dermal neurofibromas and plexiform neurofibromas. A frequent question from patients related to neurofibromas is: Why do clinical trials focus on plexiform neurofibromas, while there are no clinical trials in progress for dermal neurofibromas? Many patients feel that dermal neurofibromas are an underappreciated feature of NF.
The basis for focusing on plexiform neurofibromas thus far in clinical trials centers on three issues: first, complications of plexiforms are often more serious than for dermal neurofibromas and can sometimes be life-threatening; second, the several mouse models for testing drug effectiveness in plexiform neurofibromas are better established than the model currently available for dermal neurofibromas; and the technology for measuring dermal neurofibromas is not as advanced as for plexiforms, making it more difficult to determine the effectiveness of a specific drug on tumor growth. The good news is that the UAB NF Program has worked with collaborators recently to establish the validity of a measurement technique for dermal neurofibromas, and this method will enable the development of future clinical trials focused on testing the effectiveness of drugs in slowing or reversing the growth of these types of tumors.
In providing a more thorough explanation about the future of clinical trials for dermal neurofibromas, it’s first helpful to understand the significant differences between dermal and plexiform neurofibromas. Dermal neurofibromas are soft, benign tumors that develop under the skin. These tumors typically appear after puberty and grow slowly over a period of time. While they are variable in size and number, dermal neurofibromas can be disfiguring in some patients, causing embarrassment and problems with self-esteem. In fact, the unpredictability of dermal neurofibromas can be the most daunting aspect of this NF feature; some individuals have few or none, while others’ bodies may be completely covered. Many women with NF1 experience increased growth of neurofibromas during pregnancy, suggesting that hormonal changes may be related to their development.
The treatment approach for dermal neurofibromas is dependent on the number and location of tumors, although the most common approach is to leave them alone due to their benign nature and the low risk of medical problems. The most common treatment is surgical removal of individual tumors using either conventional plastic surgery, laser treatment, or a procedure called electrodessication that uses an electrical current to remove a large number of tumors at one time. While these treatments can be effective, each can leave scarring and none of the options prevents additional tumor development.
Plexiform neurofibromas are congenital tumors that often first appear in infancy or early childhood as a soft swelling under the skin. Affecting about 50% of people with NF1, these tumors are frequently larger and usually involve multiple branches of large nerves. Depending on their location, plexiform neurofibromas can lead to abnormal bone growth or pressure on nerves, blood vessels, or organs. For example, plexiform neurofibromas along the spine can compress the spinal cord, leading to weakness, pain, and sometimes paralysis. Surgical removal can reduce the overall size of the tumor, although it will not stop the tumor from growing.
Because the symptoms of plexiforms can be urgent and potentially life-threatening, this feature has been given greater priority over dermal neurofibromas in clinical trials. Plexiform and dermal neurofibromas are similar at the cellular level, however, so the hope is that some treatments for plexiforms may also be effective for dermal neurofibromas.
Until recently, the challenge in testing the effectiveness of specific drugs for the treatment of dermal neurofibromas has centered on the difficulty of obtaining accurate measurements of these tumors. Unlike plexiforms that grow quickly and can be measured relatively easily with imaging studies, the slower growth rate and configuration of dermal neurofibromas make them difficult to measure accurately.
In collaboration with a research group in Brazil, scientists in the UAB NF Program have tested a measurement method over the past several years that recently has been validated as providing an accurate estimate of dermal neurofibromas (Publication). Using adhesive paper frames with a 10 cm x 10 cm window cut-out, a group of patients’ dermal tumors were documented and measured by attaching the paper frame to a specific region identified by a physical landmark that was photographed; this procedure allowed us to measure growth of dermal neurofibromas over a period of time.
This recently validated measurement technique for dermal neurofibromas has opened the door to conducting clinical trials focused on testing medications to treat this feature that is problematic for so many NF patients. We are now exploring the possibility of conducting a small, independent pilot trial to determine the effectiveness of a treatment for dermal neurofibromas. Also, we have plans to design a secondary arm of a clinical trial for plexiform neurofibromas that would test the effectiveness of the medication on dermal neurofibromas. As a secondary endpoint within this trial, individuals with plexiform neurofibromas would undergo measurements of dermal neurofibromas over a period of time to determine if the medication has had an effect on slowing the growth.
We still do not know when there will be effective treatments for the various aspects of neurofibromatosis. Those with dermal neurofibromas should know that this aspect of the condition is not being ignored, and I am hopeful that clinical trials for dermal tumors will become a reality soon.
The basis for focusing on plexiform neurofibromas thus far in clinical trials centers on three issues: first, complications of plexiforms are often more serious than for dermal neurofibromas and can sometimes be life-threatening; second, the several mouse models for testing drug effectiveness in plexiform neurofibromas are better established than the model currently available for dermal neurofibromas; and the technology for measuring dermal neurofibromas is not as advanced as for plexiforms, making it more difficult to determine the effectiveness of a specific drug on tumor growth. The good news is that the UAB NF Program has worked with collaborators recently to establish the validity of a measurement technique for dermal neurofibromas, and this method will enable the development of future clinical trials focused on testing the effectiveness of drugs in slowing or reversing the growth of these types of tumors.
In providing a more thorough explanation about the future of clinical trials for dermal neurofibromas, it’s first helpful to understand the significant differences between dermal and plexiform neurofibromas. Dermal neurofibromas are soft, benign tumors that develop under the skin. These tumors typically appear after puberty and grow slowly over a period of time. While they are variable in size and number, dermal neurofibromas can be disfiguring in some patients, causing embarrassment and problems with self-esteem. In fact, the unpredictability of dermal neurofibromas can be the most daunting aspect of this NF feature; some individuals have few or none, while others’ bodies may be completely covered. Many women with NF1 experience increased growth of neurofibromas during pregnancy, suggesting that hormonal changes may be related to their development.
The treatment approach for dermal neurofibromas is dependent on the number and location of tumors, although the most common approach is to leave them alone due to their benign nature and the low risk of medical problems. The most common treatment is surgical removal of individual tumors using either conventional plastic surgery, laser treatment, or a procedure called electrodessication that uses an electrical current to remove a large number of tumors at one time. While these treatments can be effective, each can leave scarring and none of the options prevents additional tumor development.
Plexiform neurofibromas are congenital tumors that often first appear in infancy or early childhood as a soft swelling under the skin. Affecting about 50% of people with NF1, these tumors are frequently larger and usually involve multiple branches of large nerves. Depending on their location, plexiform neurofibromas can lead to abnormal bone growth or pressure on nerves, blood vessels, or organs. For example, plexiform neurofibromas along the spine can compress the spinal cord, leading to weakness, pain, and sometimes paralysis. Surgical removal can reduce the overall size of the tumor, although it will not stop the tumor from growing.
Because the symptoms of plexiforms can be urgent and potentially life-threatening, this feature has been given greater priority over dermal neurofibromas in clinical trials. Plexiform and dermal neurofibromas are similar at the cellular level, however, so the hope is that some treatments for plexiforms may also be effective for dermal neurofibromas.
Until recently, the challenge in testing the effectiveness of specific drugs for the treatment of dermal neurofibromas has centered on the difficulty of obtaining accurate measurements of these tumors. Unlike plexiforms that grow quickly and can be measured relatively easily with imaging studies, the slower growth rate and configuration of dermal neurofibromas make them difficult to measure accurately.
In collaboration with a research group in Brazil, scientists in the UAB NF Program have tested a measurement method over the past several years that recently has been validated as providing an accurate estimate of dermal neurofibromas (Publication). Using adhesive paper frames with a 10 cm x 10 cm window cut-out, a group of patients’ dermal tumors were documented and measured by attaching the paper frame to a specific region identified by a physical landmark that was photographed; this procedure allowed us to measure growth of dermal neurofibromas over a period of time.
This recently validated measurement technique for dermal neurofibromas has opened the door to conducting clinical trials focused on testing medications to treat this feature that is problematic for so many NF patients. We are now exploring the possibility of conducting a small, independent pilot trial to determine the effectiveness of a treatment for dermal neurofibromas. Also, we have plans to design a secondary arm of a clinical trial for plexiform neurofibromas that would test the effectiveness of the medication on dermal neurofibromas. As a secondary endpoint within this trial, individuals with plexiform neurofibromas would undergo measurements of dermal neurofibromas over a period of time to determine if the medication has had an effect on slowing the growth.
We still do not know when there will be effective treatments for the various aspects of neurofibromatosis. Those with dermal neurofibromas should know that this aspect of the condition is not being ignored, and I am hopeful that clinical trials for dermal tumors will become a reality soon.
Birmingham Family Affected by NF Recognized at CTF BeNeFit II Gala in Detroit, and Frequently Asked Patient Questions Regarding NF Clinical Trials
By: Bruce Korf
Published Date: Jan 06
The previous year drew to a close with the recognition of an inspirational family affected by NF who has shown unique courage, determination, and leadership in facing the challenges so familiar to other NF families. On November 22, 2014, a well-known Birmingham family in the NF community – Renie and Philip Moss and their children, Philip and Helen – received the prestigious Strength and Honor Award at the Children’s Tumor Foundation (CTF) BeNeFit II in Detroit, Michigan. The well-deserved recognition of this special family is based on their leadership role in establishing the Alabama chapter of CTF and their ongoing, tireless dedication to NF-related education, fundraising, and outreach. With more than 1,100 people in attendance, the superhero-themed gala raised approximately $3 million for CTF, the major source of patient advocacy and research support for all forms of NF in both adults and children. A brief video of the Moss family’s story and Renie’s and Philip’s reflections of the gala and the Strength and Honor Award can be found on the CTF web site.
As a new year begins, we at UAB continue our commitment to advancing and facilitating research for all forms of neurofibromatosis. In support of this commitment, UAB serves as the national coordinating center for the NF Clinical Trials Consortium, a collaborative group of 17 medical centers across the country (and one in Australia) dedicated to conducting clinical trials of the most promising drug therapies for all forms of neurofibromatosis. During the NF Clinical Trials Consortium steering committee meeting held last month in Baltimore, discussions were held regarding selection criteria for topics of upcoming clinical trials. Frequently, two specific questions that arise from NF patients regarding clinical trials are: Why are the entry criteria for clinical trials so strict?; and Why aren’t more clinical trials conducted for more features of NF?
Regarding the first question, it is understandable that many NF patients are interested in participating in clinical trials to assist in advancing research and to receive drug therapies that might be beneficial in treating a specific feature of NF. The purpose of a clinical trial is to conduct a test of a specific medication to determine if it has a potential benefit. It’s important to understand that clinical trials must be conducted according to strict protocols, and in the case of new drugs, the trials are monitored by the FDA. Also, data have to be collected with strict adherence to the protocols to ensure that results are valid and usable. If a trial proves to be effective, a specific drug could be made available to a wide number of people, instead of just the few individuals who participated in a specific trial. Strict entry criteria must be maintained to ensure the validity and reliability of the clinical trial, which in the long run benefits the entire NF community. These criteria include: A confirmed diagnosis of NF; the confirmed presence of the NF characteristic(s) being investigated in the trial; and the absence of a prohibitive medical history, such as reduced kidney or liver function or other medical conditions that could compromise the study results or endanger the study participant. Because of these strict entry criteria, some NF patients are not eligible for a certain clinical trial. While this can be disappointing for these patients, it is important to remember that accepting only those patients into the trial who fit the specific criteria ensures the reliability of the trial and safeguards the potential of making a specific beneficial drug available to larger number of NF patients.
Some NF patients find it frustrating that the complications they are experiencing may not be the subject of a clinical trial and often ask how the focus of a clinical trial is determined. This is an important question, and it should be emphasized that we are interested in conducting clinical trials for all forms of NF. Because financial resources for conducting clinical trials are limited, with the minimum average cost of a trial in the hundreds of thousands of dollars, decisions regarding the focus of a clinical trial are made according to specific criteria. We are also mindful of the fact that the NF patient community is relatively small, and we want to make sure that clinical trials are done for the most promising treatments, so that we don’t overwhelm the community with trials that have little chance of working. Generally, features that are potentially life-threatening are given greater priority, such as plexiform neurofibromas and malignancies. The NF Clinical Trials Consortium Steering Committee determines the focus of a clinical trial based on the following criteria: The degree to which a specific feature of NF is problematic or life-threatening; the availability of a drug that might be effective (based on previous animal model studies); and the prevalence and availability of patients with the NF feature. The recommendations of the Steering Committee are then reviewed by an external scientific review panel and also by an external oversight committee appointed by the Department of Defense, which is the sponsor for the Consortium.
In using specific definable criteria for selecting the focus of clinical trials and the participants to whom drug therapies are administered, we’re ensuring that the results of these important studies are valid, reliable, and can ultimately be used to identify the most promising drug therapies for all forms of neurofibromatosis.
As a new year begins, we at UAB continue our commitment to advancing and facilitating research for all forms of neurofibromatosis. In support of this commitment, UAB serves as the national coordinating center for the NF Clinical Trials Consortium, a collaborative group of 17 medical centers across the country (and one in Australia) dedicated to conducting clinical trials of the most promising drug therapies for all forms of neurofibromatosis. During the NF Clinical Trials Consortium steering committee meeting held last month in Baltimore, discussions were held regarding selection criteria for topics of upcoming clinical trials. Frequently, two specific questions that arise from NF patients regarding clinical trials are: Why are the entry criteria for clinical trials so strict?; and Why aren’t more clinical trials conducted for more features of NF?
Regarding the first question, it is understandable that many NF patients are interested in participating in clinical trials to assist in advancing research and to receive drug therapies that might be beneficial in treating a specific feature of NF. The purpose of a clinical trial is to conduct a test of a specific medication to determine if it has a potential benefit. It’s important to understand that clinical trials must be conducted according to strict protocols, and in the case of new drugs, the trials are monitored by the FDA. Also, data have to be collected with strict adherence to the protocols to ensure that results are valid and usable. If a trial proves to be effective, a specific drug could be made available to a wide number of people, instead of just the few individuals who participated in a specific trial. Strict entry criteria must be maintained to ensure the validity and reliability of the clinical trial, which in the long run benefits the entire NF community. These criteria include: A confirmed diagnosis of NF; the confirmed presence of the NF characteristic(s) being investigated in the trial; and the absence of a prohibitive medical history, such as reduced kidney or liver function or other medical conditions that could compromise the study results or endanger the study participant. Because of these strict entry criteria, some NF patients are not eligible for a certain clinical trial. While this can be disappointing for these patients, it is important to remember that accepting only those patients into the trial who fit the specific criteria ensures the reliability of the trial and safeguards the potential of making a specific beneficial drug available to larger number of NF patients.
Some NF patients find it frustrating that the complications they are experiencing may not be the subject of a clinical trial and often ask how the focus of a clinical trial is determined. This is an important question, and it should be emphasized that we are interested in conducting clinical trials for all forms of NF. Because financial resources for conducting clinical trials are limited, with the minimum average cost of a trial in the hundreds of thousands of dollars, decisions regarding the focus of a clinical trial are made according to specific criteria. We are also mindful of the fact that the NF patient community is relatively small, and we want to make sure that clinical trials are done for the most promising treatments, so that we don’t overwhelm the community with trials that have little chance of working. Generally, features that are potentially life-threatening are given greater priority, such as plexiform neurofibromas and malignancies. The NF Clinical Trials Consortium Steering Committee determines the focus of a clinical trial based on the following criteria: The degree to which a specific feature of NF is problematic or life-threatening; the availability of a drug that might be effective (based on previous animal model studies); and the prevalence and availability of patients with the NF feature. The recommendations of the Steering Committee are then reviewed by an external scientific review panel and also by an external oversight committee appointed by the Department of Defense, which is the sponsor for the Consortium.
In using specific definable criteria for selecting the focus of clinical trials and the participants to whom drug therapies are administered, we’re ensuring that the results of these important studies are valid, reliable, and can ultimately be used to identify the most promising drug therapies for all forms of neurofibromatosis.
Highlights of NF Family Day and Encouraging Developments from an International NF Meeting
By: Bruce Korf
Published Date: Oct 20
I’m pleased to report another successful Neurofibromatosis Symposium was held at the UAB Hugh Kaul Genetics Building on September 27th. Entitled “NF Family Day 2014: Learning & Thriving Together,” this half-day, free event was co-sponsored by UAB and the Children’s Tumor Foundation (CTF). The focus of the event – also known as NF Family Day – was to provide NF patients and their families with a range of information about NF through a series of brief presentations, including an overview of neurofibromatosis, an update on clinical trials and research advances, and patient advocacy. Also, a well-known patient advocate in the Birmingham NF community, Renie Moss, and Kristen Stanley from CTF gave presentations about the work of CTF and also the NF registry. The NF registry (https://nfregistry.patientcrossroads.org) was established by CTF in 2012; its purpose is to help notify NF patients who may be eligible for clinical trials or other research studies and to determine the frequency of specific NF characteristics. A highlight of this year’s NF Family Day was the opportunity for patients and their families to tour two UAB laboratories involved in NF-related research – the Medical Genomics Laboratory, which has performed the largest number of NF mutation tests of any laboratory in the world, and another laboratory developing animal models of NF1 mutations. These tours gave patients and families a firsthand, “insider” look at the promising research initiatives being conducted at UAB with the overall goal of finding and testing effective treatments for NF.
In addition to providing patients and families with important information about NF, a primary purpose of this event is to give families an opportunity to meet and interact with one another. Many of these families haven’t previously had the chance to speak with other families affected by NF, and it’s very meaningful for them to be able to talk to and learn from others with similar experiences and challenges. Many NF families attending the Symposium find that having the opportunity to meet other families in our community affected by NF is one of the most helpful aspects of the event. It’s rewarding to know that the annual NF Family Day can help to facilitate these important, supportive connections among NF families.
In early September, two UAB colleagues and I attended the 16th European Neurofibromatosis Meeting in Barcelona, Spain. Held every two years, this meeting assembles more than 100 international clinicians and researchers in the field of neurofibromatosis to present the most current research and clinical advances. Dr. Ludwine Messiaen, director of the UAB Medical Genomics Laboratory, chaired a session at the meeting and presented an overview of her NF-related research involving the pursuit of genotype-phenotype correlations and identification of novel disease-predisposing genes. Visiting UAB professor and clinician Dr. Xioajie Hu from Shanghai, China, also attended. Dr. Hu, a plastic surgeon, has been working with us since April with the goal of establishing an NF clinic and research program upon his return to Shanghai in a few months.
During the meeting, I was honored to chair a session on quality of life issues in NF and to give an overview of our UAB NF research program, including current clinical trials of promising NF medications and the development of mouse models of actual human NF1 mutations with the goal of testing medications that may restore function to the mutated gene or gene product. Overall, the meeting underscored the robust international efforts currently in progress to generate new research initiatives focused on indentifying effective NF treatments. It was encouraging to be a part of this global, collaborative effort that promotes and fosters an exchange of ideas among members of the NF scientific community.
In addition to providing patients and families with important information about NF, a primary purpose of this event is to give families an opportunity to meet and interact with one another. Many of these families haven’t previously had the chance to speak with other families affected by NF, and it’s very meaningful for them to be able to talk to and learn from others with similar experiences and challenges. Many NF families attending the Symposium find that having the opportunity to meet other families in our community affected by NF is one of the most helpful aspects of the event. It’s rewarding to know that the annual NF Family Day can help to facilitate these important, supportive connections among NF families.
In early September, two UAB colleagues and I attended the 16th European Neurofibromatosis Meeting in Barcelona, Spain. Held every two years, this meeting assembles more than 100 international clinicians and researchers in the field of neurofibromatosis to present the most current research and clinical advances. Dr. Ludwine Messiaen, director of the UAB Medical Genomics Laboratory, chaired a session at the meeting and presented an overview of her NF-related research involving the pursuit of genotype-phenotype correlations and identification of novel disease-predisposing genes. Visiting UAB professor and clinician Dr. Xioajie Hu from Shanghai, China, also attended. Dr. Hu, a plastic surgeon, has been working with us since April with the goal of establishing an NF clinic and research program upon his return to Shanghai in a few months.
During the meeting, I was honored to chair a session on quality of life issues in NF and to give an overview of our UAB NF research program, including current clinical trials of promising NF medications and the development of mouse models of actual human NF1 mutations with the goal of testing medications that may restore function to the mutated gene or gene product. Overall, the meeting underscored the robust international efforts currently in progress to generate new research initiatives focused on indentifying effective NF treatments. It was encouraging to be a part of this global, collaborative effort that promotes and fosters an exchange of ideas among members of the NF scientific community.
Upcoming NF Family Day, Research Advances, and a Special Award for a Birmingham Family Affected by NF
By: Bruce Korf
Published Date: Sep 04
As part of our ongoing commitment to providing comprehensive, integrated care for children and adults with all forms of NF, I’m pleased to announce the addition of a new nurse, Linda Woodard, to our team of specialists in the UAB NF Clinic. With a background in patient care and clinical research, Ms. Woodward will play an integral role in caring for patients in our clinic as well as coordinating clinical trials and protocols as part of our NF research program.
Neurofibromatosis patients and their family members will have an important opportunity to learn more about NF – including research and clinical care – at the upcoming Neurofibromatosis Symposium to be held at the UAB Hugh Kaul Genetics Building on September 27th. Co-sponsored by UAB and the Children’s Tumor Foundation (CTF), this year’s symposium is entitled “NF Family Day 2014: Learning & Thriving Together.” The focus of this half-day, free event is to provide NF patients and their families with key information in a series of presentations on a range of NF-related topics including: an overview of neurofibromatosis; updates on clinical trials and other research advances; patient advocacy; and a question-and-answer session. Breakfast and lunch will be provided, and those who attend will also have the opportunity to tour two UAB laboratories currently involved in NF-related research. Childcare will be available for the convenience of our families. While there is no cost to attend, reservations should be made by September 25th by emailing hande@uab.edu. We always look forward to this invaluable opportunity to provide information, support, and answers to NF patients and families, especially those who may be facing a new diagnosis.
Our NF research program continues to make significant strides in clinical trials and in the laboratory. UAB serves a dual role both as a member of and the national coordinating center for the NF Clinical Trials Consortium, a collaborative group of 17 medical centers across the country dedicated to conducting clinical trials of the most promising drug therapies for all forms of neurofibromatosis. As a member of the Consortium, we are currently launching two clinical trials to test medications for possible effectiveness in shrinking plexiform neurofibromas, tumors that involve multiple branches of large nerves. These drugs have shown some activity in shrinking plexiform neurofibromas in mouse models, and the hope is that these medications will also be proven effective in human clinical trials. Details can be found on the NF Clinical Trials Consortium website (http://www.uab.edu/nfconsortium/).
In the laboratory, scientists at UAB are continuing to advance research related to the development of mouse models of actual human NF1 mutations in the hope of testing medications that may restore function to the mutated gene or gene product. We have made significant progress in study of a model with a premature stop mutation, a common type of NF1 mutation that leads to a non-functional gene product. This is the first time this specific type of mutation has been studied in a mouse model, and it was chosen by our research team because medications are currently available that can read through a premature stop mutation, restoring function to the gene and allowing the production of some functional protein. In testing such drugs on cells from these mice, we have demonstrated some slight restoration of normal gene function and production of the neurofibromin protein. This is a hopeful sign, and the next phase of the research will be to test the medications on the mice themselves, with the goal of determining whether they slow the growth of neurofibromas in the animals.
To further advance our program’s research goals, we have formed a collaborative partnership with Southern Research Institute, with the objective of screening new medications that may be effective in the treatment of NF. Based on Southern Research Institute’s significant accomplishments in the area of drug discovery, we anticipate this partnership to be productive in helping us to identify new medications that may hold promise as future NF treatments.
I’d like to extend a special note of congratulations to Renie and Philip Moss and their children, Helen and Philip, for being selected to receive the prestigious 2014 Strength and Honor Award at the upcoming NF fundraising event in Detroit, Michigan, in November. This special Birmingham family is being recognized for their integral role in establishing the Alabama chapter of the Children’s Tumor Foundation (CTF) as well as their ongoing leadership of the Alabama CTF and dedication to NF-related education, fundraising, and outreach. This recognition is well-deserved, and we in the Birmingham community are very proud of the Moss family’s tireless mission to raise awareness of NF with the overall goal of helping to fund research aimed at finding effective treatments.
Lastly, the UAB NF Program will soon launch a Facebook page to help patients, families, and others interested in neurofibromatosis stay informed about our program’s activities related to patient care, research, education, and special events. We also look forward to using the new page as a vehicle to communicate with patients and families about important developments in the NF community.
Neurofibromatosis patients and their family members will have an important opportunity to learn more about NF – including research and clinical care – at the upcoming Neurofibromatosis Symposium to be held at the UAB Hugh Kaul Genetics Building on September 27th. Co-sponsored by UAB and the Children’s Tumor Foundation (CTF), this year’s symposium is entitled “NF Family Day 2014: Learning & Thriving Together.” The focus of this half-day, free event is to provide NF patients and their families with key information in a series of presentations on a range of NF-related topics including: an overview of neurofibromatosis; updates on clinical trials and other research advances; patient advocacy; and a question-and-answer session. Breakfast and lunch will be provided, and those who attend will also have the opportunity to tour two UAB laboratories currently involved in NF-related research. Childcare will be available for the convenience of our families. While there is no cost to attend, reservations should be made by September 25th by emailing hande@uab.edu. We always look forward to this invaluable opportunity to provide information, support, and answers to NF patients and families, especially those who may be facing a new diagnosis.
Our NF research program continues to make significant strides in clinical trials and in the laboratory. UAB serves a dual role both as a member of and the national coordinating center for the NF Clinical Trials Consortium, a collaborative group of 17 medical centers across the country dedicated to conducting clinical trials of the most promising drug therapies for all forms of neurofibromatosis. As a member of the Consortium, we are currently launching two clinical trials to test medications for possible effectiveness in shrinking plexiform neurofibromas, tumors that involve multiple branches of large nerves. These drugs have shown some activity in shrinking plexiform neurofibromas in mouse models, and the hope is that these medications will also be proven effective in human clinical trials. Details can be found on the NF Clinical Trials Consortium website (http://www.uab.edu/nfconsortium/).
In the laboratory, scientists at UAB are continuing to advance research related to the development of mouse models of actual human NF1 mutations in the hope of testing medications that may restore function to the mutated gene or gene product. We have made significant progress in study of a model with a premature stop mutation, a common type of NF1 mutation that leads to a non-functional gene product. This is the first time this specific type of mutation has been studied in a mouse model, and it was chosen by our research team because medications are currently available that can read through a premature stop mutation, restoring function to the gene and allowing the production of some functional protein. In testing such drugs on cells from these mice, we have demonstrated some slight restoration of normal gene function and production of the neurofibromin protein. This is a hopeful sign, and the next phase of the research will be to test the medications on the mice themselves, with the goal of determining whether they slow the growth of neurofibromas in the animals.
To further advance our program’s research goals, we have formed a collaborative partnership with Southern Research Institute, with the objective of screening new medications that may be effective in the treatment of NF. Based on Southern Research Institute’s significant accomplishments in the area of drug discovery, we anticipate this partnership to be productive in helping us to identify new medications that may hold promise as future NF treatments.
I’d like to extend a special note of congratulations to Renie and Philip Moss and their children, Helen and Philip, for being selected to receive the prestigious 2014 Strength and Honor Award at the upcoming NF fundraising event in Detroit, Michigan, in November. This special Birmingham family is being recognized for their integral role in establishing the Alabama chapter of the Children’s Tumor Foundation (CTF) as well as their ongoing leadership of the Alabama CTF and dedication to NF-related education, fundraising, and outreach. This recognition is well-deserved, and we in the Birmingham community are very proud of the Moss family’s tireless mission to raise awareness of NF with the overall goal of helping to fund research aimed at finding effective treatments.
Lastly, the UAB NF Program will soon launch a Facebook page to help patients, families, and others interested in neurofibromatosis stay informed about our program’s activities related to patient care, research, education, and special events. We also look forward to using the new page as a vehicle to communicate with patients and families about important developments in the NF community.
A Successful NF Walk, Two Key NF Conferences, and Rapid Research Progress
By: Bruce Korf
Published Date: Jul 16
When the last blog was posted, plans were underway for the first annual Birmingham NF Walk to raise funds for the Children’s Tumor Foundation (CTF), the major source of patient advocacy and research support for all forms of NF in both adults and children. I’m pleased to report that this landmark event for our city, held in Birmingham’s Railroad Park on May 10th, was wildly successful and raised more than $50,000 for CTF. In spite of an overcast day with an imminent threat of rain, more than 100 people participated in the NF Walk, which represents the first time that a major organized fundraiser for CTF was held in our city. While Birmingham is nationally recognized for NF research and clinical care, the success of this event has now put our city on the map in terms of fundraising for NF. The overall success of this inaugural fundraiser is due to the dedication and tireless efforts of a group of Birmingham families who have been affected by NF; I believe that their fundraising success will serve as a springboard for future events that will help support critical NF research focused on the development of breakthrough treatments.
Dr.Korf with Philip Moss at the NF walk
In early June, I attended two national events, held simultaneously in Washington, D.C., that have great importance in the NF community. The NF Conference, the preeminent annual event in the arena of neurofibromatosis research, attracts several hundred clinicians and researchers from around the world to present the latest developments in NF research and clinical care. The NF Forum, for which I had the privilege of serving as co-chair this year, is an annual meeting of patients and families that provides information about the latest medical advances in neurofibromatosis as well as support and advice for those living with NF. This was the second time these two events have been held adjacent to each other; for me, the most memorable aspect was the dinner attended by participants in both events. This joint session provided a unique forum for researchers and clinicians to learn firsthand about the concerns and struggles of those living with NF and gave patients and families the opportunity to meet those in the scientific community dedicated to developing new treatments. Dr. Francis Collins, who discovered the first NF1 gene and serves as director of the National Institutes of Health (NIH), was the speaker during this powerful session. It was an inspirational experience to learn how both of these groups are working, in different ways, toward the same end – finding effective treatments for NF. I was also impressed by the number of new ideas for treatments that are currently being tested in mouse models and clinical trials. Many of the ideas discussed in previous meetings a few years ago have been implemented in the research setting are now the central focus of scientists’ work in the laboratory.
I came away from these meetings excited about the level of patient engagement and grateful for the ability to provide patients with information to help them become more involved in their care. This will also be a focus of the UAB NF Clinic in the coming months – to increase the involvement of patients in their own care by implementing a Board of Advisors comprised of patients and families to provide feedback that will ensure the Clinic is functioning in a way that best meets their needs. Also, we’re exploring the development of smart phone and tablet apps to assist patients in documenting and storing information about their own care that can also be shared with clinicians to expedite communication and enhance patient care. There will be more details to share in future blogs.
Our robust NF research program continues make significant advances. A primary goal of our research efforts is to develop therapies to restore function to mutated genes and their associated proteins. A specific type of gene mutation, called a premature stop mutation, is responsible for 20% of NF1 cases and is of particular interest to our research team. Genetic scientists at UAB have developed mouse models of a premature stop mutation for NF1, which is the first time this specific type of mutation has been studied in a mouse model. Drugs are available that can partially overcome the effects of premature stop mutations. The hope is that such drugs will prove effective in restoring function to mutated genes for those with NF1 caused by premature stop mutations. Our mouse models will allow UAB scientists to study the NF1 disease process as it develops in the animals and to test the drugs that hold promise in restoring function to mutated genes. Within the past two months, the mice have begun to develop tumors, and our scientists will soon begin a research study to test the effectiveness of a drug on the tumors. This research has progressed rapidly and holds great potential for establishing the effectiveness of a new treatment for NF1.
A new website and Birmingham's first NF walk
By: Bruce Korf
Published Date: May 07
These are times of great hope in the NF community, and times of exciting growth in Birmingham and at the UAB NF Program. In the larger world of NF research, the pipeline of new treatments continues to expand, from basic science laboratories to animal models to clinical trials. Here, though, I'd like to focus on what is happening in Birmingham, and thereby explain the rationale for launching this new website and blog.
We timed the launch of this website to coincide with the first Birmingham walk to raise funds for the Children's Tumor Foundation (CTF), the major source of patient advocacy and research support for all forms of NF in both adults and children. I participate in events for CTF around the country and had always hoped to be able to see something big happen in my home town. Now, thanks to the dedication and huge efforts of a group of families led by Philip and Renie Moss (and check out the video on our site featuring the Moss family!), Wes and Stephanie Waldrop, James and Ginny Rediker, and Bill and Nikki Robbins, something very big is about to happen here. I'd like to think that Birmingham is on the map for NF research and clinical care; now it will be as well for fundraising by our patients, their families, and their friends.
Our NF Clinic is one of few anywhere that provides care for patients with all forms of NF at any age. There are over a thousand people with NF in Alabama, and I suspect that either Dr. Lane Rutledge or I have seen a good proportion of them in our clinic over the years. What's more, almost every week patients are seen who traveled long distances – across the state, from neighboring states, across the country, and even from other continents, to be seen. One of my goals for the clinic this year is to increase the involvement of patients in their own care, using educational tools and the web portal for our electronic health record to help make this happen. I will report on progress in the coming months.
The UAB Medical Genomics Lab, led by Dr. Ludwine Messiaen, is recognized around the world as the leader in genetic testing for all forms of NF. The lab has characterized thousands of mutations, and now has been awarded a contract from CTF to search for genotype-phenotype correlations: Can we identify mutations that predict specific NF complications – or the lack of complications, for that matter? This has the potential to improve care and also to shed light on how some of these complications come about. Also this year, the Medical Genomics Lab discovered a new genetic cause of Schwannomatosis – mutation in a gene designated LZTR1. This work was published recently in Nature Genetics, the most prestigious scientific journal in genetics, and opens the way towards diagnostic testing and new approaches to study of the biology of Schwannomatosis.
During the past several years, thanks in large part to generous contributions from major supporters of our program, we have vastly expanded our research aimed at developing new treatments for NF. Given our experience in NF mutation testing, we have deep knowledge of the various types of mutations that occur in the NF genes. Our goal now is to develop treatments that will restore function to the mutated gene or its protein product. Similar work has been successful in cystic fibrosis, where a new drug was developed that targets a particular mutation, which is now approved for clinical use by the FDA. We are developing new animal models and patient-derived cell cultures for this work, and recently some of the models have produced tumors that will allow us to do drug testing. I will provide more details about this exciting work in a future blog.
There is a lot more to talk about – like our role as coordinating center for the Department of Defense funded NF Clinical Trials Consortium, which launched a trial for patients with NF2 earlier this year and soon will launch two more for plexiform neurofibromas. This, too, I'll discuss in the near future. For now, I hope you will share our excitement – for the prospects for NF treatment, for the growth of our clinical and research programs, and most of all for the inspiring energy of patients and families in our community. I hope that you will find this new and expanded website helpful – we welcome your feedback, your involvement, and your support!
