Drug Discovery Initiative

2016 DDI Awards Application

The 2016 DDI-A Application is now available. 

Please review the eligibility guidelines HERE. 
Once you begin your application you can save your work and return to it at any time using the log-in link that you will receive via email. Please do not return to this link to continue your application as your work will not be saved; you must return to the link you receive via email to continue your work in your saved application. 
To begin a new DDI application click HERE
Applications are due Monday, April 18, 2016 at 5:00 p.m.


Please refer to the Frequently Asked Questions below for further information.
We look forward to receiving your application!




Do I have to sign the patent policy in order to apply?

Yes. You must sign the patent policy at the time of application.

What if my tech transfer office wants to negotiate the patent policy before I sign it?

If you think your tech transfer office will want to negotiate the patent policy, you must send the patent policy to them immediately and have them contact CTF to negotiate the terms immediately.

Can I still apply for a DDI even if I don't share tools in the CTF Discovery toolbox?

Yes. However, we strongly encourage you to share tools, techniques, protocols and collaborate in order to advance the field.

Do I have to sign the MTA in order to apply?

We encourage applicants to share their tools in the DDI toolbox. To do so, you must agree to the terms of the MTA by signing Form F. This is a sample MTA, and will be fully completed by you and the recipient at the time of transfer of tools.

What is ADDF-ACCESS and how does it relate to the DDI application?

Alzheimer's Drug Discovery Foundation (ADDF) and the Children's Tumor Foundation (CTF) are in a partnership to provide CTF's scientific network access to a virtual network of drug discovery experts and contract research organizations (CROs) through the ADDF ACCESS program. The program offers scientist tools to determine if they need a CRO, how to choose a CRO, how to manage a relationship with a CRO, education on the drug discovery process, and an online forum for discussions with experts. The portal allows users to customize their search for CROs based on drug discovery area and resources for guidance on CRO selection and research design.

We have entered this partnership to provide this resource to our NF scientists, especially those in the drug discovery field. The DDI exists to accelerate drug discovery for NF. By partnering with CRO, we can make the path to the clinic more efficient.


To learn more about how partnerships with CROs will streamline drug discovery efforts, please refer to this recent publication in Nature Reviews Drug Discovery:


How do I determine if I need a CRO?

Deciding when to outsource depends on a variety of factors, including in-house capabilities and the need for expert guidance. Why should you outsource?

  • Access to targeted compound libraries
  • Early stage development expertise in the following areas:
  • Assay development
  • Medicinal chemistry
  • Pharmacology
  • Pharmacokinetics and Pharmakodynamics
  • ADME, safety and toxicology studies
  • Cost and time efficiency – Evaluate overhead costs of resources, equipment, adherence to standard operating procedures (SOP), and personnel certifications for highly specialized tasks versus the costs of outsourcing. Consider how much time your personnel devote to drug discovery tasks and how long it will take to develop SOPs
  • Key platform technologies – Access to automated equipment that produce reliable, robust, and reproducible data (i.e. behavioral monitoring systems, microscopy, in vivo imaging, HPLC units, liquid handlers, plate readers)
  • Regulatory compliance – Later-stage IND-enabling studies require good lab practice (GLP) and good manufacturing practice (GMP) conditions in compliant laboratories.
  • For more information, please refer to the ADDF ACCESS Resource Center: When to Outsource


How do I choose a CRO?

Please refer to the ADDF ACCESS Resource Center: Evaluating and Selecting CROs: http://www.alzdiscovery.org/addf-access/resource-center/evaluating-and-selecting-cros

Does the cost of the CRO come out of my DDI award amount?

No, CTF will pay the CRO directly and it does not come out of your DDI award amount.



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.

CTF Discovery Toolbox

(NOTE: Updates to this document are pending.) The new CTF Discovery 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. It is expected that, unless legally prevented from doing so, DDI Awardees will make tools developed under their DDI award available through the CTF Discovery Toolbox. CTF also strongly encourages researchers to voluntarily submit tools that are created outside the scope of their funding from CTF.  To improve the use and sharing of such tools, we introduced 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 available for download in the application. Investigators who will decide to make their tools available in the toolbox will be notified by CTF if the tool is requested, and CTF will coordinate the final agreement between the two parties.  

A link to download the CTF Discovery Toolbox Submission/Request form will be posted here shortly

DDI Recipients 2011-2016

2016 DDI Awardees

  • Marco Giovannini, MD, PhD, David Geffen School of Medicine, UCLA, Preclinical safety and efficacy evaluation of long-term anti-VEGFA treatment administration in a GEM model of NF2-related schwannoma.
    Neurofibromatosis type 2 (NF2) is an autosomal dominant genetic disorder characterized by growth of tumors along nerves. These tumors are generally resistant to radiation and chemotherapy; the surgical approaches to treatment typically have significant neurological complications. Case reports and clinical trials have reported that bevacizumab (Avastin), a monoclonal antibody against vascular endothelial growth factor (VEGF), can induce both tumor regression and hearing improvement in patients with NF2-associated vestibular schwannomas. Effect of Avastin has not been tested in the mouse models of NF2 schwannoma that are currently used to screen new drugs for clinical trials in patients. We will test bevacizumab in the NF2 mouse schwannoma model to analyze its efficacy in terms of tumor shrinkage and hearing performance. Setting the Avastin response baseline in mice will allow prioritization of new drugs by comparing their efficacy to that of Avastin, therefore helping the choice of new drug candidates for clinical trials in NF2 patients.

  • Andrea Rasola, PhD, University of Padova, Italy,Targeting the mitochondrial chaperone TRAP1 to inhibit plexiform neurofibroma growth
    Neurofibromatosis type 1 (NF1) is a tumor predisposing genetic syndrome affecting about one in 3,000 individuals worldwide. One of its most troublesome features is that patients develop multiple tumors, called neurofibromas, which can cause pain and in some cases can be disfiguring and, even more importantly, can become highly aggressive malignant cancers. At present no specific treatment exists for tumors arising in NF1 patients, in spite of a wealth of knowledge on the molecular alterations that lead to their onset and growth. For this reason we think that is compelling to change the point of view on the problem of neurofibroma development, for exploring aspects that have been underestimated up to now and that might reveal instrumental in the achievement of effective therapeutic approaches. In the last few years it is becoming increasingly clear that changes in cell metabolism constitute a driving force for the growth of many tumor types. We have applied these observations to neurofibromas, whose metabolism has been poorly investigated, finding that these tumors undergo profound metabolic alterations. Importantly we have found that TRAP1, a protein that has a crucial function in the control of the energy metabolism of tumor cells, is mandatory for neurofibroma growth. The aim of this project is therefore the identification of molecules that, by inhibiting TRAP1, might block neurofibroma progression. These compounds might be the first step in the development of selective and effective anti-neoplastic drugs for NF1 patients.

  • Verena Staedtke, MD, PhD, Johns Hopkins University, Evaluation of Mebendazole as Chemoprevention in a Neurofibromatosis 1 Transgenic Mouse Model
    Neurofibromatosis Type 1 (NF1) is a genetic disease caused by mutations in a tumor suppressor gene, which is responsible for the regulation of a major growth pathway, Ras. In NF1 patients the Ras pathway is hyperactivated leading to uncontrolled cell growth and the development of various tumors. The most common tumors are neurofibromas, which arise from the peripheral nerve sheath and occur in almost all of the NF1 patients. Although neurofibromas are benign, a subset of these - so-called plexiform neurofibromas - can transform into a malignant peripheral nerve sheath tumor (MPNST), which is a highly aggressive cancer that affects 10-15% of patient with NF1. These tumors are very difficult to treat and have a five-year survival rate as low as 20%. The best outcomes are achieved when the MPNST was completely surgically removed, however, even then cures are rare. The process by which a benign neurofibroma transforms into a deathly MPNST is not completely understood yet. It is assumed that neurofibromas accumulate certain genetic changes over time that further activate the Ras pathway as well as other critical cell signaling pathways allowing the cells to grow uncontrollably and form new vasculature to increase the blood supply to the tumor. Because this transformation occurs stepwise over a long period of time, it makes an ideal target for chemoprevention, i.e. the use of drugs to reduce the risk of the development of cancer. Chemoprevention has been used very successfully in other cancers, where pre-existing high-risk lesions occur, as with polyps in colorectal cancer or certain fibromas in breast cancer; however, it remains a largely unexplored area in NF1.

    Because the development of new agents for chemoprevention is a long, difficult and expensive process, a potential strategy to circumventing these challenges is to discover new uses for drugs with an established track record of safe and long-term use in humans (repurposing). We have shown that mebendazole (MBZ), an FDA-approved drug originally intended to treat parasitic worm infections, can significantly slow the growth of highly aggressive brain cancers in mice. Furthermore, MBZ is able to block numerous critical steps in the development of NF1-related MPNSTs, such as the inhibition of important cellular growth pathways including the Ras pathway that underlies NF1, and the formation of new blood vessels. By blocking these key pathways by which benign cells transform into an invasive cancer, MBZ could reduce the need of more aggressive surgical or toxic interventions and, if successful, could significantly lower death rates in this NF1 patient population. Perhaps most importantly, MBZ has a lengthy track record of safe long-term human use with few side effects, if any, which makes it well suitable as a chemoprevention agent.

    Thus, we propose to repurpose MBZ for preventing the transformation of a benign neurofibroma to a deathly MPNST. First, we will evaluate the chemopreventative effect of MBZ in a MPNST mouse model that has many similar features to human NF1 patients to assess both the efficacy and the long-term safety. Next, we will test the combined use of MBZ with anti-inflammatory agents to enhance this protective effect in a MPNST mouse model. Anti-inflammatory drugs targeting on the COX-2 pathway have shown benefits in colorectal cancer syndromes previously. The goal of this proposal is to collect sufficient data to support a clinical trial for MBZ therapy as a chemoprevention agent in NF1 individuals with high-risk plexiform neurofibromas. If successful, the results will have an immediate impact on patient care by reducing the cancer frequency with the highest death rate among NF1 patients - MPNST.

  • Jeffrey Field, PhD, University of Pennsylvania,MPNST profiling and screening: extension for exome sequencing of the cell lines screened.
    The most life threatening symptom that NF patients develop are tumors, some of which become cancerous. Using funds from the DDI, we developed a course where our students screened 130 NF relevant drugs against 9 NF1 cancer cell lines and two NF2 cell lines and additionally screened thousands of drugs against representative NF1 and NF2 cell lines. We found that the cell lines showed some common response patterns as well as differences that we cannot explain. Our data will be more informative if we knew the mutations that each cell line harbored, so we can correlate the sensitivity to drugs that we tested with the mutations in each cell and use the mutations to identify new drugs to test. To find the mutations, we seek additional funds to determine the DNA sequences of all of the genes in our cell lines. We are working with an informatics group, Sage Bionetworks, to organize and analyze the data and develop searchable web-based applications to make the data public.

2015 DDI Awardees 

  • Dr. Nancy Ratner, Cincinnati Children's Hospital Medical Center,Mechanisms of Resistance to MEK Inhibition in Neurofibroma
  • Dr. Thomas A. Look, M.D., Dana-Farber Cancer Institute,Drug discovery for NF1-associated malignant peripheral nerve sheath tumors using the zebrafish model
  • Dr. Joseph Kissil, Scripps Research Institute,Assessing the anti-tumor activity of crizotinib in NF2-deficient meningioma
  • Dr. Andrea McClatchey, Massachusetts General Hospital, Expanded testing of centrosome-unclustering drugs in NF2-mutant tumors
  • Dr. Alexander Schulz, Leibniz Institute for Age Research - Fritz Lipmann Institute (FLI),Establishing a protein replacement therapy for the treatment of Schwann cell-derived nerve sheath tumors
  • Dr. Lei Xu, Massachusetts General Hospital – Research,Combining immunotherapy and antiangiogenic therapy in NF2 schwannoma model
  • Dr. Steven Lewis Carroll, Medical University of South Carolina,Combinatorial Therapy with Receptor Tyrosine Kinase Inhibitors for Malignant Peripheral Nerve Sheath Tumors
  • Dr. Jeffrey Field, University of Pennsylvania,MPNST profiling and screening: an experiment in Research based Education

2014 DDI Awardees

  • Miriam Smith, PhD, University of Manchester , Treatment of Neurofibromatosis Type 2 (NF2) by Exon Skipping
  • Andrea McClatchey, PhD, Harvard Medical School, Preclinical Investigation of Centrosome Unclustering Drugs in NF2-mutant Schwannoma
  • David Largaespada, PhD, University of Wisconsin-Madison, Targeting Hyaluronic Acid for NF1-associated Tumors
  • Gregory Riggins, MD, PhD, Johns Hopkins University, Testing Combinations of FDA-approved Agents with and without Radiation Therapy in an NF2 Schwannoma Murine Model

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

2012 DDI Awardees

  • Chris Maxwell, University of British Columbia and Conxi Lazaro, Catalan Institute of Oncology-IDIBELL, Targeting NF‐1 associated MPNST with aurora kinase Inhibitors
  • Filippo Giancotti, Memorial Sloan-Kettering Cancer Center, Preclinical Efficacy of the Neddylation Inhibitor MLN4924 in Neurofibromatosis Type II
  • Nancy Ratner, Cincinnati Children's Hospital Medical Center,In Vivo Testing of Anti-Oxidants in Nf1 CNS
  • Micheal Brownstien, Pisces Therapeutics, LLC, Small Molecule Ras Inhibitor for the Treatment of Neurofibromatosis Type 1 (NF1)
  • Rajesh Khanna, Indiana University, Assessment of peptide-based disruptors of the neurofibromin and CRMP-2 interaction as novel analgesics for NF1
  • Andrea McClatchey, Massachusetts General Hospital,Heterogeneity of drug response in NF2-deficient schwannomas

2011 DDI Awardees

  • Cristina Fernadez-Valle, Ph.D., University of Central Florida, Preclinical testing of the mTORC1 inhibitor Rapamycin in NF2 meningioma mouse models
  • Jan Friedman, MD, Ph.D., University of British Columbia, Cytokine inhibitors for the treatment of NF1 Vasculopathy
  • Xu Wu, Ph.D., Harvard Medical School/ Massachusetts General Hospital, Small Molecule Library of Inhibitors of YAP Nuclear Localization in NF2 Schwannoma, Astrocytoma, Meningioma Cells
  • David Largaesapada, Ph.D., University of Minnesota*, Drug combinations for NF1 Plexiform Neurofibroma and MPNST (Builds on previous in vitro DDI Award)
  • David Wiemer, Ph.D., University of Iowa, Advanced DDI Award to optimize Schweinfurthins for NF1 Astrocytoma (Builds on previous DDI Award)

*Dr. Largaespada’s Award is funded by the Texas Neurofibromatosis Foundation through CTF.

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