July 10, 2018: One of the hallmarks of the complex syndrome Neurofibromatosis type 1 (NF1) are cutaneous neurofibromas (cNF). cNF are tumors involving the skin that affect up to 99 percent of adults with NF1. They are a major source of emotional and social distress, as well as intermittent, but chronic, physical symptoms, such as pain and itching. Although cNF are not predisposed to becoming malignant, adult patients with NF1 identify cNF as their greatest burden and the “perceived disease visibility” related to cNF is significantly associated with depression, psychosocial distress and decreased quality of life.
There is no known way to prevent these tumors and current treatments are limited to regional, procedure-based approaches with uncertain effectiveness. For too long, cNF has been a major unmet need for NF1 patients. The Neurofibromatosis Therapeutic Acceleration Program (NTAP) at the Johns Hopkins University School of Medicine, working in collaboration with scientific partners around the globe, is seeking to change things.
In order to tackle cNF, NTAP organized a summit designed to define the state of the field, to prioritize research questions, and to create a community of thinkers invested in developing effective cNF therapeutics. Experts from the leading ranks of academia, industry, and government (with and without explicit experience with NF1 or cNF), representing a wide range of scientific and clinical backgrounds, participated in the summit. A set of consensus recommendations was formulated, which represents the critical first step to define key issues and create a plan to address them. The fruit of the cNF summit is a ‘research roadmap’ for targeting cNF that is captured in five manuscripts published in the July 10 online issue of Neurology®, the medical journal of the American Academy of Neurology.
An introductory paper, titled ‘Creating a Comprehensive Research Strategy for Cutaneous Neurofibromas,’ provides an overview of NF1 associated cNF and the core scientific areas discussed at the summit: the challenges in reaching consensus about the clinical definition of cNF, the key biological questions to address, considerations for developing therapies for cNF, and considerations for the design of clinical trials targeting cNF. Brief descriptions of each of these papers can be accessed here.
The learnings from the summit are now being acted upon. NTAP is supporting nine discovery and translational research projects based on outcomes of the summit that address topics such as identifying the human cells of origin for cNF and understanding how these cells influence cNF initiation and progression, (2) understanding how nerve and tumor microenvironment contribute to cNF development, (3) identifying and elucidating the genetic and molecular factors that underlie cNF initiation and progression, and (4) generating preclinical model systems to elucidate disease biology and enable preclinical therapeutic testing. There is also an initiative to create a commonly accepted classification scheme validated in a prospective study with dermatopathologists, neuropathologists and NF1 clinicians, that accurately describes each tumor type by its clinical appearance, pathological, molecular and histological features. Finally, a clinical trial is underway assessing a new technique for measuring cNF that may enable more rapid testing in clinical trials.
The publication of this supplement in Neurology® is one of the key accomplishments of the initial steps to “jumpstart” research in cNF. Dr. Sharad K. Verma, Director of Research and Development for NTAP, shared “NTAP is committed to uniting the scientific community and invigorating research in cNF, which for too long has been an unmet need for NF1 patients. We are excited to be collaborating with the global community of researchers and funders to take cNF beyond this inflection point and inspire the scientific community to direct energy and resources towards developing the first drug-based therapies for cNF.” The publication of these manuscripts in Neurology®, the launch of cNF focused research projects, and the cNF clinical classification effort are all major initiatives sponsored by NTAP to advance the possibility of meaningful treatments for cNF.
The Neuroﬁbromatosis Therapeutic Acceleration Program (NTAP) is a philanthropy-driven research program based at the Johns Hopkins University School of Medicine. NTAP is focused on accelerating the development of therapeutics for NF1 tumors by fostering collaboration, promoting the open and timely sharing of results, and streamlining research models. This work was supported in part by Bloomberg Philanthropies (www.bloomberg.org). Its contents are solely the responsibilities of the authors and do not necessarily represent the oﬃcial views of Bloomberg Philanthropies or The Johns Hopkins University. The Johns Hopkins University is an academic institution based in Baltimore, Maryland.