Background and Overview
Cutaneous neurofibromas (cNF) are multicellular tumors involving the skin that are one of the hallmark findings of neurofibromatosis type 1 (NF1). They affect >90% of adults with NF1 and are a major source of emotional and social distress as well as intermittent but, chronic physical symptoms such as pain and itching (Huson S, et al, Brain, 1988). The tumors typically appear in adolescence and commonly increase in number and size over time. Although cNF are not medically predisposed to malignant transformation and are rarely associated with functional limitations, these tumors are highly damaging to people with NF1 via their disfigurement. In adults with NF1, perceived disease visibility is significantly associated with depression, psychosocial distress, quality of life (QoL) impairment and negative body experience for attractiveness/self-confidence (Page PZ, Am J Med Gen, 2006; Wolkenstein P, Arch Dermatology, 2001). There is currently no known way to prevent these tumors from developing and current treatments are limited to regional procedure based approaches that have uncertain efficacy. As this is an unmet need and patients with NF1 often identify these tumors as their greatest burden within the complex syndrome of NF1, the development of therapies to prevent, stabilize or reduce these tumors is a priority.
Current knowledge about the underlying mechanistic, structural, and genetic factors responsible for the formation of human cutaneous neurofibromas (cNF) is limited. This represents a major hurdle to understanding disease initiation and pathogenesis, and ultimately the ability to develop effective treatments for these tumors. To overcome this barrier, the Neurofibromatosis Therapeutic Acceleration Program (NTAP) is investing in cNF research and invites proposals focused on NF1 associated cNF pathophysiology with special focus sought in the following areas:
1. Identifying the human cells of origin for cutaneous neurofibromas and understanding how these cells influence and drive cNF initiation and pathogenesis.
2. Understanding how both nerve and tumor microenvironment contribute to cNF pathogenesis.
3. Identifying and elucidating the specific genetic and molecular factors that underlie cNF initiation and progression.
4. The generation of preclinical model systems that elucidate disease biology and enable preclinical therapeutic testing.
Funding: NTAP anticipates funding up to 10 awards via this initiative. Awards are anticipated to be for projects lasting from 12-36 months, but with appropriate justification, projects can be outside of this timeframe. The anticipated funding is $300,000 per project with detailed budget justification. There is flexibility based on the project and appropriate budget justification. Investigators can be from academia, government, or private sector, and international candidates are welcomed. Indirect costs are not to exceed 10% of the total direct funds.
Next Steps: Investigators who are interested in submitting a proposal for any one of the cited research areas should first review the following detailed descriptions of the associated tasks for these research topics as noted in the ‘Appendix’ section, and then submit a two page letter of intent per the format described in the ‘Submissions’ section by 5p EST on May 12, 2017. If advanced for consideration of award, notification of a request for a full proposal will be made to the primary investigator by May 31, 2017.
Data Sharing Policy:
Information about NTAP’s data sharing guidelines can be found here.