Need for Effective Treatments

I’d like to focus this month’s blog post on a discussion of cutaneous neurofibromas, which are benign tumors that can grow on nerves throughout the body in some individuals with NF1. Typically beginning around the time of puberty, these tumors grow from small nerves either in or under the skin and appear as small bumps on the surface of the skin or as purplish spots when the tumors occur underneath the skin.  Although these tumors are sometimes also referred to as “dermal neurofibromas,” NF clinicians and scientists at a recent meeting of the Neurofibromatosis Therapeutic Acceleration Program (NATP) emphasized the need to move away from using this term in favor of the term “cutaneous neurofibromas.” The dermis is actually not the layer of the skin from which neurofibromas originate, while “cutaneous” is a general term referring to the skin and is therefore a more accurate term for these tumors.

In the past, we have found that obtaining funding for clinical trials of cutaneous neurofibromas has been somewhat difficult. Because these tumors are non-malignant and not life-threatening, the question often posed is:  Why is it necessary to treat cutaneous neurofibromas? Conversely, plexiform neurofibromas are much more serious and sometimes life-threatening due the risk of malignancy and the possibility of compression of the airway or the spine.  However, it is also true that cutaneous neurofibromas may be unfairly trivialized in their impact on the lives of individuals with NF. We receive numerous inquiries asking why cutaneous neurofibromas are not the subject of clinical trials.  Data indicate that quality of life for people with cutaneous neurofibromas can be significantly impaired. There are sometimes cosmetic concerns in a major sense, as these tumors may be quite disfiguring.  Also, the tumors may itch, can sometimes bleed, and even cause pain. 

Research Focused on Cutaneous Neurofibromas

A longitudinal study has been in progress at UAB for the past several years focused on understanding how cutaneous neurofibromas grow and change over time. As part of the study, 22 participants have had their neurofibromas counted and measured every three months. Our NF Program Genetics Counselor, Ashley Cannon, MS, PhD, CGC, assumed the principal investigative role in the study when she joined our program in 2015 and has now completed an analysis of eight years of quantitative data on many of the original study participants.  Dr. Cannon recently presented the study findings at the conference of the American College of Medical Genetics and Genomics (ACMG) in Phoenix and is preparing the results for upcoming publication. 

These findings will also serve as the basis of an upcoming clinical trial at UAB that will test the effectiveness of a systemic treatment for cutaneous neurofibromas administered in the form of a pill.  While development of a topical treatment was considered, it can be difficult to formulate a compound that permeates the skin layer. Also, for some people, cutaneous neurofibromas are too widespread on the body for a topical treatment to be effective.  Additional information about the trial and details about upcoming recruitment can be found at www.clinicaltrials.gov.

In other research for cutaneous neurofibromas, we are exploring other potential treatments for future clinical trials of cutaneous neurofibromas.  We’re also working to find ways to restore function to mutated genes or gene products, which could provide new ways of treating these tumors. Researchers at UAB are currently studying the more than 3,000 NF mutations contained in the library of the UAB Medical Genomics Laboratory to determine whether particular mutations increase the likelihood for cutaneous neurofibromas to occur. We know of two mutations that do not produce neurofibromas of any type. There are other mutations that don’t produce cutaneous neurofibromas but do produce neurofibromas deep inside the body (plexiform neurofibromas). We are currently developing animal models and other types of model systems to understand the characteristics of specific mutations with the goal of developing new treatments for cutaneous neurofibromas.