Drug Discovery Initiative

2014 DDI Awards - Application Available

We MUST RECEIVE completed Applications by 5:00 p.m. ET
September 2, 2014

Applications received after this date will NOT be reviewed.

Requests to negotiate PATENT POLICY should be received no later than August 15, 2014

Submission Process

  1. Click on the Download Application button in order to save the Application Form PDF document on your computer
  2. Once completed, you can submit the Application Form by clicking on the Submit button available in the same document
* the form is available as an interactive PDF and requires Adobe Reader.
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Updated March 2014: A more streamlined and efficient path to clinical development can be accomplished by partnering with contract research organizations (CROs). The Alzheimer’s Drug Discovery Foundation (ADDF) and The Children’s Tumor Foundation (CTF) have entered a partnership to provide CTF’s scientists access to a virtual network of drug discovery experts and CROs through the ADDF ACCESS program. Through the effective selection of CROs and use of their services, NF researchers may be able to accelerate their research and bring novel therapies to patients faster. Read more about the partnership Alzheimer's-Drug Discovery Foundation.

Drug Discovery Toolbox

Updated March 2014: The completely new DDI Toolbox is an online list of tools for NF drug discovery - mouse models, cell lines, candidate drugs, etc. for investigators to share resources and establish collaborations. Listing your tools in the Toolbox makes other researchers aware of tools available for NF research, and could provide an opportunity for you to identify future collaborators. To improve the use and sharing of such tools, we introduced this year a new regulation that will make it more transparent and easier to access to any researcher. We added an upfront agreement to CTF standard conditions for the transfer of the tools, as outlined in the MTA in Appendix F of the DDI application. Keep in mind that the tool will be made available only to those who will apply for a new Drug Discovery Initiative Award with the purpose to use it as part of their DDI application.

DDI Recipients 2010-2014

2014 DDI Awardees 

  • Miriam Smith, PhD, University of ManchesterTreatment of Neurofibromatosis Type 2 (NF2) by Exon Skipping
    Neurofibromatosis type 2 (NF2) is a neurogenetic disorder that predisposes patients to develop tumors of the nervous system. It is known that NF2 disease is caused by mutation of the NF2 gene. Most of these mutations are found in the coding regions, called exons, that code for the NF2 protein, but 1-2% of pathogenic NF2 mutations are found in non-coding regions and disrupt the process by which cells generate a functional protein from the gene. Recently, a study has shown that this process can be restored in cells derived from patients with this kind of mutation, using molecules called morpholinos. It has also been shown for muscular dystrophy, that "skipping" of some exons can restore expression of a functional protein. We plan to test the hypothesis that this system could also be used to rescue mutations in coding regions of NF2, where 98-99% of small mutations are found. We will create a series of constructs containing the coding regions of the gene, but with individual exons deleted. We will then express them in cells and compare their function to normal NF2, containing the entire coding region, to determine the viability of this hypothesis. For deletion constructs with comparable function to normal NF2, we then plan to design morpholinos that can restore expression of viable proteins endogenously in cells.

  • Andrea McClatchey, PhD, Harvard Medical School, Preclinical Investigation of Centrosome Unclustering Drugs in NF2-mutant Schwannoma
    The successful development of a therapeutic strategy for any tumor requires a clear therapeutic window in which the drug negatively impacts tumor cells but not normal cells. Overduplication of centrosomes, a cellular organelle that is essential for normal cell division, occurs broadly across different tumor types and has therefore received much recent attention as a feature that distinguishes tumor from normal cells. This has led to the development of drugs that specifically target and kill cells that harbor too many centrosomes. We recently identified a key role for Merlin in controlling the distribution and number of centrosomes within cells. Thus NF2-mutant tumor cells exhibit centrosome overduplication and defects in centrosome localization. Most recently we have found that acute mutation of NF2 alone is sufficient to promote these centrosome defects in Schwann/schwannoma cells. We believe that this represents an Achilles heel for schwannomas and that they will be exquisitely sensitive to this new class of drugs that targets cells with overduplicated centrosomes. The goal of this proposal is to test this hypothesis.

  • David Largaespada, PhD, University of Wisconsin-Madison, Targeting Hyaluronic Acid for NF1-associated Tumors
    Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive tumors that can occur in the general population, but are frequently seen in patients with neurofibromatosis type 1 (NF1). With an incomplete understanding of the genetic basis of MPNSTs, the current standard treatment includes surgical resection, high-dose chemotherapy, and/or radiation. To date, most therapies have failed to demonstrate effectiveness against plexiform neurofibromas and MPNSTs, and MPNSTs remain the leading cause of death for NF1 patients. Recently, we showed that a combination of two drugs, RAD001 and PD-901, which target two pathways known to drive tumor growth were effective at treating mice that develop Schwann cell tumors and model the genetics and tumor characteristics of human patients. These drugs given in combination reduced the number, size, and aggressiveness of tumors, and resulted in a prolonged lifespan and improved motor skills of the mice. While the results of these studies were promising, the mice eventually succumb to their tumors, demonstrating that more work needs to be done to find a more effective therapy. Upon further investigation, we found that both human and mouse Schwann cell tumors have fewer blood vessels and are very physically hard due to the presence of high amounts of hyaluronic acid within the tumors. Experiments showed that when drugs are given to these mice, the drug is unable to get into the core of the tumor due to the lack of blood flow and physical properties of the tumors. This phenomenon has been seen in pancreatic tumors, and a drug, PEGPH20, has been shown to safely and effectively break down hylaronic acid and improve the drug delivery and efficacy of chemotherapy in these patients. Our goal is to test the safety and efficacy of RAD001 and PD-901 combination therapy, which we previously showed to improve disease in mice with Schwann cell tumors, when given with PEGPH20 to improve the ability of these drugs to get to the tumors and kill tumor cells.

  • Gregory Riggins, MD, PhD, Johns Hopkins University, Testing Combinations of FDA-approved Agents with and without Radiation Therapy in an NF2 Schwannoma Murine Model
    Neurofibromatosis type 2 (NF2) is a tumor suppressor syndrome characterized by multiple intracranial and spinal schwannomas, meningiomas, and ependymomas. Although NF2 is relatively rare, its hallmark tumors, meningiomas and schwannomas, represent the most common adult neural tumors. The principal treatments consist of neurosurgical removal of the tumors and surgical treatment of these lesions. Drugs with therapeutic efficacy have been sparse and, discouragingly, there remains no consensus for the treatment of these tumors. Preliminary results of early, ongoing, clinical studies show no harm, but also, possibly no overwhelming efficacy. Unfortunately, there is little data about the use and efficacy of therapeutic compounds in combination with radiation therapy for the treatment of NF2 tumors. Over the past two years, we have developed methods to evaluate toxicity and efficacy of radiation therapy in an NF2 schwannoma murine model. In this proposal we intend to examine the safety and efficacy of multi-modal therapy including radiation combined with compounds that effect tumor growth through multiple pathways, including kinase inhibtors and mTOR inhibitors. We will first test the toxicity and efficacy of these compounds as monotherapy and then will test their effect together with and without radiation therapy. Efficacy will be evaluated for additive or synergistic effect. Animals receiving radiation therapy will be evaluated for the development of secondary malignancies as well. This rapid in vivo screening method will assess toxicity and efficacy of these compounds with and without radiation therapy in the mouse model of NF2 schwannoma. In these studies we hope to provide a platform for validating established anti-proliferative and cytostatic agents combined with radiotherapy to facilitate translational studies for this rare but debilitating disease.

 2013 DDI Awardees

  • Cristina Fernandez-Valle, PhD., University of Central Florida, Creation of Human Merlin‐Null Schwann Cells for NF2 Studies
  • Jean Nakamura, PhD., University of California, San Francisco, Identification of novel targets in NF1 cancers by drug sensitivity profiling
  • Lei Xu, PhD., Massachusetts General Hospital,Effect of TGF-beta blockade in recurrent NF2 vestibular Schwannoma
  • Charles Yates, PhD., Indiana University, Testing Periostin-Cre NF2 Conditional Knockout Mouse for Potential Treatment Compounds Useful for NF2
  • Kate Quinlan, PhD., The Sydney Children's Hospitals Network, Mouse NF1 muscle models for MEKi drug screening and DDI toolkit
  • Aaron Schindeler, PhD. The Sydney Children's Hospitals Network, Addition of a murine CPT model to the DDI Toolkit

2013 Drug Discovery Initiative

The application process for the 2013 the Drug Discovery Initiative awards has closed. The submission process for the 2014 DDI awards will open in late February. Please check back soon for more information.


The Children's Tumor Foundations is pleased to announce that from 2012 the DDI Award levels will increase:

  • $25,000 for in vitro studies
  • $50,000 for in vivo studies
  • $75,000 for Advanced in vivo studies 

Contact Us

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Phone: 212-344-6633