In 2006, the Children's Tumor Foundation formulated a strategic plan to accelerate neurofibromatosis (NF) research. Over the past five years, the Foundation has enacted this plan by funding over $10 million in research programs targeted toward ending neurofibromatosis through the development of effective therapies. Within the next five years (2012-2016) CTF has committed $30 million to a research investment plan to facilitate initiatives.
Clinical Trials - Five years ago there were only two NF clinical trials in progress. Today, there are 26 ongoing NF-Specific clinical trials, 44 NF clinics nationwide, and more than 50 promising compounds in preclinical drug development.
NF Conference - Initiated 20 years ago, the NF Conference is the premier annual event in the neurofibromatosis research and clinical calendar. In 2012, over 300 clinicians and researchers from around the world convened to present the latest developments in NF research and clinical care. The Conference includes high-profile keynote speakers from related disciplines such as cancer and neuroscience, serving to stimulate thought and build connections between NF and other disorders.
NF Registry - The Children's Tumor Foundation launched an NF Patient Registry in 2012. The purpose of this registry is to find people who may be eligible for clinical trials or other research studies being conducted in the field of neurofibromatosis, and to determine the commonality of specific NF characteristics. Please go to www.nfregistry.org for more information and to get involved.
The Foundation has collaborated with Thomson Reuters to generate disease maps to show how Foundation funds are spent. In this project, Thomson Reuters created disease schemas for neurofibromatosis types 1 and 2 and schwannomatosis in order to enable the mapping of project management and finance data on the disease pathways involved in each of the disorders. The schemas were created in Pathway Map Creator, a pathway drawing software application of Thomson Reuters. The pathway maps give a snapshot of the different processes involved in each disorder, and by clicking on the dollar signs, the list of grants funded by the Foundation can be seen. By moving from disease schema to dashboard, funding in the different aspects of the research and development process can be seen. The schemas can be easily adjusted and/or converted to other formats. The disease maps will be updated on a yearly basis in collaboration with Thomson Reuters.
- The Drug Discovery Initiative Awards program is focused on seed funding preclinical drug testing studies on neurofibromatosis in cell or animal models, and is one of the most successful Children's Tumor Foundation programs to date. Since this program began in 2006, we have funded over 45 DDI Awards focused on preclinical testing of drug therapies for all aspects of NF1, NF2 and schwannomatosis, from learning disabilities to tumor growth to pain. This has been an investment for the Foundation of $1 million, but we have seen our investment leveraged, as awardees have gone on to secure over $5 million in follow-on funding from federal and other sources.
- The Children's Tumor Foundation has made significant contributions to advancing schwannomatosis research through grant funding, including establishing the first Schwannomatosis International Database, as well as organizing a series of International Schwannomatosis Workshops to spur collaboration. In 2005, the Children's Tumor Foundation spearheaded the publication of the first diagnostic criteria for schwannomatosis.
- The Children's Tumor Foundation invests in endpoint development through a Clinical Research Awards program. Currently our funded projects include developing a computerized test for more accurate assessment of learning disabilities trials; identifying a blood biomarker of NF1 status; and developing measures of response for optic pathway glioma trials.
- From 2003-2006, CTF provided pilot funding to help develop the NF Tumor Metrics Service (www.nftumormetrics.org) at Massachusetts General Hospital (MGH). This technology allows for volume rather than linear measurement of tumors, a much more accurate assessment. Due to the success of the pilot study, CTF continues to fund this service and it will be rolled out, on a limited basis, to all current Neurofibromatosis Clinic Network (NFCN) sites.
- Dr. Chris Moertel, Director of the Children's Tumor Foundation Neurofibromatosis Clinic Network Affiliate Clinic at the University of Minnesota, is making progress in what has largely been an elusive area for clinical researchers - the development of vaccines to treat brain tumors. Dr. Moertel pioneered these studies by successfully halting brain tumor growth in a dog which had been injected with cell matter harvested from its own tumor. He has since advanced the trials into seven patients with malignant glioma who have been treated with vaccine made from their own tumor matter. It is very early days but these studies look promising and will continue. Vaccines have been challenging to develop but if successful would reduce the need for using chemotherapy drugs. The target is currently malignant cancer but looking ahead there may be potential to apply a similar approach to neurofibromatosis tumors.
- Malignant peripheral nerve sheath tumors (MPNSTs) are among the tumors that can occur in NF1, but these malignancies are particularly challenging to treat and control. One reason for this is that MPNST cells appear to undergo changes that make them resistant to traditional treatments such as chemotherapy. Current Children's Tumor Foundation Young Investigator Awardee Dr. Thomas de Raedt, a postdoctoral fellow in the laboratory of Dr. Karen Cichowski at Harvard Medical School, has published a paper this week in leading journal 'Cancer Cell' describing his work in mice, showing a new and seemingly highly effective way to treat MPNSTs via a 'double-hit' - using two drugs in combination. Dr. de Raedt and his colleagues combined the drug rapamycin, which targets the cell signaling element mTOR, with the drug IPI-504, which targets another cell signaling element called HSP90. In the face of this treatment, the mouse MPNSTs underwent dramatic shrinkage. The tumors also underwent what is termed autophagy, where the cells die and collapse under stress so rapidly that they create spaces where the tumors were. The success of this approach comes from the fact that combining rapamycin and IPI-504 leads to a collapse of cell structures called the endoplasmic reticulum (ER) and mitochondria which together, constitute the energy source or 'engine' of the cell. By shutting down the ER and mitochondria, the cell dies. We look forward to seeing the next steps of this exciting finding.
- Learning disabilities, ranging from mild to severe, may affect as many as two-thirds of those with NF1. Since 2007, CTF has funded three learning disabilities workshops to bring together the experts in the field. These learning disabilities were poorly understood for a long time, until around six years ago when groundbreaking research from the lab of Dr. Alcino Silva (UCLA) showed that the drug Lovastatin, traditionally prescribed for cholesterol lowering, appeared to correct NF1-related learning disabilities in mice genetically engineered to have these deficits. Over the past few years, Dr. Maria Acosta (Children's National Medical Center) and her colleagues have taken on the daunting task of translating this 'mouse result' to humans, by bringing Lovastatin to clinical trials to treat NF1-related learning disabilities. Dr. Acosta has now published the outcome of this trial in the journal Pediatric Neurology. This was a Phase I study (Phase I studies are designed to assess the safety of the drug). 24 children received Lovastatin over a three-month period, and no safety issues were seen. Furthermore, and although this study was not designed to fully evaluate the effect of the drug, the children on the study showed overall improvements in verbal and non-verbal memory functions. These exciting findings will pave the way to the Phase II trial in which the potential efficacy of Lovastatin will be thoroughly evaluated in a larger population.