Q: What prompted the creation of the foundation?
In the mid-1970s, Dr. Allan Rubenstein was a young neurologist in New York City who began seeing more and more patients and families with neurofibromatosis (NF). There was little information he could offer them, but he began talking with a nurse, Lynne Courtemanche Shapiro, who had NF. They wanted to find a way to organize the patient community, and through a serendipitous meeting on an airplane, they met lawyer Joel Hirschtritt. While Joel knew nothing of NF, he was captured by their story and agreed to help set up our predecessor, The National Neurofibromatosis Foundation, in 1978. The foundation changed its name to the Children's Tumor Foundation (CTF) in 2005 and is dedicated to improving the health and well-being of individuals and families affected by NF. Our mission is to support research and the development of effective treatments for the various forms of NF.
Q: What were the challenges in neurofibromatosis research that you felt the foundation could help address?
The history of the foundation has been in "arcs." From its inception in 1978 through the mid-1980s, it was solely focused on organizing the patient community and providing support. From the late 1980s through the mid-1990s, our research was focused on discovering the genes that cause NF. We were fortunate to fund grants in the labs of Drs. Francis Collins and Ray White, who independently discovered the NF1 gene in 1989, and Dr. Jim Gusella, who discovered the NF2 gene in the early 1990s. That led to a decade of more basic research, but also of creating animal models and cell lines.
Beginning in 2005, we began to focus on translational research, specifically preclinical testing of compounds to build a pipeline for clinical trials. While this work continues, in 2008 we developed the NF Clinic Network and began funding pilot clinical trials. We began to work with industry to fund the work that will lead to more informed, and thus better, clinical trials.Going forward, there are a number of key challenges to be faced:
- There is no clear genotype-phenotype correlation, making it impossible to predict how the NF symptoms of patients will evolve over time.
- NF is a complex disorder that can range from patients being asymptomatic to severely disabled.
The foundation's ongoing work seeks to address these issues, specifically by undertaking efforts to raise industry interest in NF and investing heavily in initiatives that allow a systems biology approach to unravel unknown disease mechanisms and identify novel targets.
Q: Can you tell us a bit about efforts like the Drug Discovery Initiative and the Preclinical Consortium and how they help overcome the barriers you've identified?
One of the more challenging barriers to be overcome has been that industry interest in NF is very low due to the fact that NF is under-recognized, and the unmet medical need of NF is unknown.
The Children's Tumor Foundation recognizes the need to set up and fund platforms that allow:
- The development of novel cell and animal models,
- The de-risking of molecules with an innovative mechanism of action that might have a benefit for NF patients, and
- The fast track testing of re-purposed drugs to help rationalize the selection of drug candidates that enter into clinical development
The Drug Discovery Initiative (DDI) and the NF Preclinical Consortium address these platforms in important ways.
DDI is a quick turn-around translational science initiative, which in addition to funding cell- and animal-model development, provides quick preclinical proof of concept testing of compounds with innovative mechanisms of action that may offer benefit to NF patients. It is meant to develop more predictive models and to de-risk innovative compounds.
The NF Preclinical Consortium (NFPC) is a consortium of academic labs that have validated NF-relevant animal models. It is a team effort toward common goals of:
- evaluating the same repurposed drug candidates in the panel of animal models for NF, and
- improving the rational selection of drug candidates that will be progressed to clinical trials.
The major hurdle that delays and often impedes NFPC and the DDI work are the materials transfer agreement negotiations between academia and industry that authorize access to the compounds.
Q: What do you consider the foundation's greatest accomplishments to date?
We are proud of a number of advancements in NF research due to Children's Tumor Foundation support:
- Two CTF awardees contributed to the discovery of the genes that cause NF;
- We helped fund the development of NF cell and mouse models;
- We established the only worldwide NF Conference (which continues to grow each year);
- CTF has established a clinic network (the Cystic Fibrosis Foundation and Multiple Myeloma Research Foundation are models to follow);
- Post-CTF funding, major governmental organizations have funded over $200 million in NF research, including from the Department of Defense's Congressionally Directed Medical Research Program (CDMRP);
- We have tried to "go smarter to the clinic" by funding rational selection of drug candidates for clinical trials;
- We have funded pilot trials;
- Numerous top journal articles have been generated with CTF funding; and
- We are engaged in an ongoing effort to raise industry interest in NF by efficiently bridging between pharma and academia.
Q: What are your top research goals for 2013, and what will it take to reach those goals?
Our primary research goals for 2013 are to:
- Attract pharma and biotech to the NF field via a collaborative business model actively bridging science to industry to patients.
- CTF offers an industry-level testing platform and the necessary tools to allow preclinical proof-of-concept testing of both existing molecules as well as innovative molecular mechanisms.
- CTF continues its active scouting for compounds that may benefit NF patients.
- CTF expands the necessary services to allow clinical trials.
- The NF Patient Registry will be expanded.
- A biobank will be launched.
- Consented efficacy outcome measure development will be funded.
- The development of FDA-approved outcome measures will be explored.
- The connection to the CDMRP clinical trials consortium will be maintained.
- The Children's Tumor Foundation will further invest in this new business model, allowing CTF to be a partner and collaborator with academia and industry, rather than only a funder. Multiple pilots along these lines are currently ongoing. The hope is that this investment will:
- Foster collaboration between labs, with academia, with other successful foundations and organizations such as FasterCures; and
- Attract new researchers to the field and invest in data sharing efforts such as NFPC and a new initiative called Synodos, a large SPORE-like proposal to tackle NF2.