Orphan Disease Center

ODC Funding Opportunities

CDKL5 Pilot Grant Program

MDBR Pilot Grant Program

High-Throughput Screening Core Pilot Grant Program

 

Improved Therapies for MPS I Pilot Grant Program

The ODC Improved Therapies for MPS I Pilot Grant Program provides a 1-2 year grant for $150,000.00 (direct costs/year) to support research on the development of improved therapies for patients with syndromes due to MPS I including Hurler, Hurler-Scheie, and Scheie. 

Background

The goal of this RFA is to support research on the development of improved therapies for patients with syndromes due to MPS I including Hurler, Hurler-Scheie, and Scheie.  Particular emphasis will be on treatments that improve aspects of the disease, which are not adequately treated by enzyme replacement therapy such as pathology in the CNS, skeletal system, eye and heart among others, as well as on biomarker discovery that can be used in the performance of clinical trials.  It is anticipated that most grants will utilize pre-clinical and clinical models of MPS I.  However, applications will also be considered that utilize models of mucopolysaccharidoses (MPS) other than MPS I if their use is scientifically justified and the data can be applied to improved therapies for MPS I.  A premium will be placed on studies whose data could be applied across a wide range of MPS diseases including MPS I.

Research topics relevant to this RFA include the following:

1) Repurposing of existing small molecule drugs for the treatment of MPS diseases.

        • Identification of existing pharmaceuticals for treatment in MPS diseases and demonstration of efficacy in cell and animal   models of MPS.  We will consider applications that propose methods to identify existing drugs that may be useful in MPS diseases using one of many possible experimental approaches, such as in vitro screens of drug libraries, and/or in silico drug identification.  We envision this to be a two-year project in which the repurposed drug candidate is identified in the first year and tested in vitro and in vivo in the second year.  The ODC will help the applicant to identify collaborators to conduct the MPS-specific animal studies if they are not experienced in this area. 
        • Clinical evaluation of therapeutics that are either approved for, or in clinical trials for, other indications.  Support will be considered for re-purposing of these drugs if pre-clinical studies support safety and potential efficacy in models of MPS.  The grant should support aspects of translation that will accelerate the path to the clinic.  Other sources of funding will likely be necessary to support this bench-to-bedside effort.  The applicant should describe and have access to all resources necessary to complete the proposed clinical trial.

2) Studies on pathogenic mechanisms of MPS diseases that: A) are directed toward the identification of novel therapeutic targets; or B) inform more effective development of molecular, gene or cell therapies. 

3) Discovery and evaluation of potential patient biomarkers that can be used to evaluate the short-term and long-term impact of therapeutics in clinical trials.  There is especially the need to find biomarkers that will be responsive to therapies that are given in combination with enzyme replacement therapies. 

4) Novel therapeutic approaches such as gene replacement therapy, genome editing, stem cells, and mRNA transfer.  Evaluation of these novel therapies must be conducted in animal models of MPS diseases. 

Eligibility

All individuals holding a faculty-level appointment at an academic institution or a senior scientific position at a non-profit institution or foundation are eligible to respond to this RFA.

To Apply

All applicants must first submit a Letter of Interest (LOI) to be reviewed for consideration of a full application submission.  Please submit this form with the uploaded files no later than 5pm (EST) on Monday, February 29, 2016. 

NOTE: FULL APPLICATION IS BY INVITATION ONLY after review/approval of LOI.  All notifications will be sent by Friday, March 4, 2016. 

In advance of submitting an LOI, it is strongly recommended that you review the complete guidelines for a full application, which can be found here:  2016 MPS I RFA Guidelines

 

CDKL5 Program of Excellence Pilot Grant Program

The ODC CDKL5 Pilot Grant Program provides a one-year grant for $150,000.00 (total cost) to support research related to CDKL5.  The number of awards may vary.

Background

CDKL5 Deficiency is a monogenic, orphan condition characterized by treatment-resistant epilepsy and severe cognitive and motor disability.  The disease is driven by the loss of a kinase called CDKL5 which is responsible for neuronal development, synapse formation and signal transmission.  The mechanism(s) by which CDKL5 deficiency leads to CNS disease is unclear.  The gene encoding this protein is located on the X chromosome with heterozygous females showing symptoms.  The disease does not exhibit neurodegeneration and animal models strongly suggest the potential for reversibility. There are no approved therapies and standard of care is not effective at managing the epilepsy or improving cognitive or motor deficits.

We are seeking grant applications that address research questions directed toward the development of treatments and/or a cure for CDKL5 deficiency.  We recognize, however, that many gaps exist in the basic understanding of CDKL5 and its role in neurologic development.  Therefore basic science projects that address these gaps are welcome as long as they are tethered to the development of a potential therapy.  While the RFA is broad in scope, priority will be given to grants that cover the following areas:

      • Development of small molecule therapeutics based on repurposing of existing drugs using in vitro screens or in silico methods.
      • Approaches to re-activate the silent CDKL5 allele on the X chromosome.
      • Identification of novel drug targets based on a better understanding of the role of CDKL5 in neurologic function and development.
      • Identification of biomarkers and/or development of clinical endpoints.
      • Advanced animal models and their use in defining pathogenesis and evaluating novel therapeutics. 
      • Novel therapeutic approaches such as gene replacement therapy, genome editing, and mRNA transfer.

Eligibility

All individuals holding a faculty-level appointment at an academic institution or a senior scientific position at a non-profit institution or foundation are eligible to respond to this RFA. Biopharmceutical companies are not eligible to apply, however, we will consider applications from contract research organizations who provide services that are responsive to the RFA.

To Apply

All applicants must first submit a Letter of Interest (LOI) to be reviewed for consideration of a full application submission.  Please submit this form with the uploaded files no later than 5pm (EST) on Monday, February 22, 2016. 

NOTE: FULL APPLICATION IS BY INVITATION ONLY after review/approval of LOI.  All notifications will be sent by Friday, February 26, 2016. 

In advance of submitting an LOI, it is strongly recommended that you review the complete guidelines for a full application, which can be found here:  2016 CDKL5 RFA Guidelines

 
Million Dollar Bike Ride Grants

All applicants have been notified of the status of their LOIs.  If you have any questions regarding the status of your LOI, please contact Samantha Charleston (scharle@upenn.edu). 

The 2015 Million Dollar Bike Ride Pilot Grant Program is now closed.  Thank you to all who participated.

For questions regarding this pilot grant program, please contact Samantha Charleston at scharle@mail.med.upenn.edu, or (215) 573-6822.

Research Focus Areas for Pilot Grants:

1) Adrenoleukodystrophy (ALD): Adrenoleukodystrophy, or ALD, is an x-linked metabolic disorder, characterized by progressive neurologic deterioration due to demyelination of the cerebral white matter. The adult form, known as Adrenomyeloneuropathy (AMN) develops in young adulthood, and in general, they progress more slowly. Beginning in their 20s and 30s, these young men exhibit neurological based motor lesions in their extremities. These lesions progress over many years and are inevitably accompanied by moderate to severe handicap. In approximately one third of these patients the central nervous system also becomes involved.

One $50,000 pilot grant is available with a focus on treatments for Adrenomyeloneuropathy (AMN), the adult form of the disease. We are interested in proposals that would provide a path towards a treatment, including advancing the understanding of what can be used as endpoints when conducting an AMN trial. This grant is made possible by Team Stop ALD and the Stop ALD Foundation.

2) Bronchiolitis obliterans: Two $50,500 pilot grants available with a focus on pediatric post-infectious Bronchiolitis Obliterans. Proposals that seek to improve understanding of the pathogenic processes involved in abnormal airway remodeling following exposure to adenovirus, mycoplasma, or other viruses or bacteria, as well as those which seek to improve clinical management and outcomes will be considered responsive. Proposals that address the development of BO as a complication of Stephens-Johnson Syndrome in the context of an airway infection with mycoplasma will also be considered.  These grants are made possible by Team Bronchiolitis Obliterans and the Children’s Interstitial and Diffuse Lung Disease Foundation. 

 3) Castleman Disease: One $63,000 pilot grant available.  We would like to investigate the role that genetics plays in HHV-8-negative or "idiopathic" multicentric Castleman disease (iMCD) by performing Whole Exome Sequencing or Whole Genome Sequencing on 20-25 patients with iMCD. In addition to sequencing the samples, the CDCN would like for bioinformatics to be performed and for a consent process to be developed that the CDCN will be able to use moving forward for future studies and biobanking purposes. This grant is made possible by Team Castleman Disease and the Castleman Disease Collaborative Network. 

4) CFTR Nonsense Mutations: Two $51,500 pilot grants available to initiate or advance research and understanding of a treatment or a cure that would impact the nonsense mutation 1282X in the CFTR gene. The research could include drug discovery or other strategies to restore CFTR function, including suppression of premature termination, modulation of nonsense-mediated decay and gene editing.  These grants are made possible by Team Emily’s Entourage and the Emily’s Entourage organization.  

5) Cystic Fibrosis: One $69,000 pilot grant available. Cystic fibrosis is a genetic condition affecting the lungs and digestive system. The grant will be awarded to advance research and understanding of a treatment or cure that would impact people carrying a nonsense mutation.  The research should include, but not be limited to, the R1158X gene mutation. This grant is made possible by Team Movin’ for Mallory: Cure Cystic Fibrosis! and the Movin’ for Mallory organization.

6) Congenital Hyperinsulinism (CHI): One $71,000 pilot grant available focusing on innovative, pre-clinical or clinical studies designed to improve the diagnosis, therapy, or quality of life for those affected by congenital hyperinsulinism.  This grant is made possible by Team Raring to Go for CHI, and Congenital Hyperinsulinism International.

 7) Duchenne Muscular Dystrophy (DMD): One $49,000 pilot grant available.  Duchenne is due to mutations in the dystrophin gene and is characterized by progressive muscle wasting, loss of ambulation, and death, most often in early adulthood.  There has been strong engagement in developing targeted therapies for Duchenne, but it is clear that a combination therapy approach will be necessary to achieve truly disease-mitigating outcomes.  Parent Project Muscular Dystrophy solicits applications on discovery and development of new platform technologies for preclinical evaluation of synergies among drugs and/or biologics to be used as combination therapies for Duchenne.  While specific candidate therapies can and should be used to develop and validate the platform technology, the successful applicant will focus on development of an innovative testing platform that can be more generally adopted for combination therapy development. Leveraging of other resources in development and validation of the platform technology is strongly encouraged. This grant is made possible by Team Bike to End Duchenne and the Parent Project Muscular Dystrophy organization. 

8) Fibrous Dysplasia/McCune Albright Syndrome: Two $58,500 pilot grants available.  FD/MAS is a rare disease caused by somatic mutations in GNAS. The mutation results in constitutive activation of the signaling protein, Gs alpha, and downstream cAMP signaling. Skeletal manifestations include bone pain, fractures, and osteomalacia/rickets.  Extraskeletal manifestations include precocious puberty, hyperthyroidism, growth hormone excess, pancreatic neoplasms, and others. The grant will be awarded to initiate or advance research and understanding of any of the manifestations of the disease or its underlying pathophysiology.  The research could involve understanding the mechanism and/or treatment of FD-related bone pain, developing animal models of any aspect of the disease, or address any of the unmet needs in FD/MAS patients. These grants are made possible by Team FD and the Fibrous Dysplasia Foundation. 

9) Generalized Lymphatic Anomaly (GLA; a.k.a. lymphangiomatosis) and Gorham-Stout Disease (GSD): Two $51,000 pilot grants are available to investigators conducting research on GSD and GLA. We are interested in proposals focused on basic science and/or clinical research on GSD and GLA.

One $101,000 pilot grant is available for a project focused on imaging deep lymphatic vessels in GLA or GSD patients with thoracic involvement. These grants are made possible by Team LGDA, the Lymphangiomatosis & Gorham’s Disease Alliance and Team LMI and the Lymphatic Malformation Institute. 

10) Lymphangioleiomyomatosis (LAM): Two $50,500 pilot grants available focusing on translational proposals with strong likelihood of future federal funding, that use LAM samples, models or patient data, and which have the potential to favorably impact human health will be given priority. Examples of desirable topic areas include identification of molecular targets, biomarker development, and biomarker driven small pilot trials. These grants are made possible by Team LAM Foundation Easy Breathers and the LAM Foundation.

 11) Mucolipidosis Type IV (ML4): One $53,000 pilot grant available to investigators conducting research on all aspects of disease research including disease pathogenesis, and clinical studies. This grant is made possible by Team Cure ML4 and the ML4 Foundation.

 12) Mucopolysaccharidoses (MPS): Two $50,500 pilot grants available.  Mucopolysaccharidoses represent a broad array of diseases due to enzyme defects that lead to abnormal metabolic storage products and multi-organ pathologies.  We are seeking applications directed to treating the central nervous system manifestations of these diseases.  These grants are made possible by Team MPS, the National MPS Society and the Ryan Foundation.   

13) Niemann Pick Type C (NPC): Two $53,500 pilot grants available. Preference will be given to research projects developing new therapies for NPC, and translational research projects that improve our understanding of the biology, pathogenesis and disease state (i.e., biomarkers or functional outcome measures to assess therapeutic impact).  This grant is made possible by Team NPC, the Andrew Coppola Foundation, Chase the Cure and iPedal4Chad.

 14) Pitt Hopkins Syndrome (PTHS): Two $50,000 pilot grants available. Pitt Hopkins Syndrome is due to a deficiency in the TCF4 gene and is characterized by severe intellectual disability and developmental delay. Other symptoms include episodic hyperventilation and/or breath-holding (55%-60%), recurrent seizures/epilepsy (40%-50%), gastrointestinal issues, and distinctive facial features. The Pitt Hopkins Research Foundation would like to focus this research on finding therapeutics and a cure for this debilitating syndrome and are not interested in natural history studies at this time. These grants are made possible by Team Pitt Hopkins Pedalers with the Pitt Hopkins Research Foundation. 

 15) RASopathies: One $53,000 pilot grant available. RASopathies are a group of genetic conditions caused by mutations in genes on the Ras-MAPK pathway. These conditions, including Noonan syndrome/Noonan-related conditions (NS), cardio-facio-cutaneous syndrome (CFC), Costello syndrome (CS), and Neurofibromatosis type 1 (NF1) share many clinical features, such as developmental delay, gastrointestinal difficulties, skeletal abnormalities, hematologic abnormalities, and growth delay. 

There are numerous anecdotal reports of individuals with a RASopathy having significant pain in various joints and parts of the body; however, this has not been formally addressed.

This grant will be awarded to initiate or advance research in further understanding of the pertinent clinical features that impact all three conditions (NS, CFC, and CS).  The research should include, but would not be limited to identifying the etiology, incidence, assessment, and management of pain in individuals with a RASopathy. This grant is made possible by Team RASopathies Network Riders and the RASopathies Network.

16) Tay-Sachs & Allied Diseases (TSAD): One $43,000 pilot grant available focusing on the diseases that fall under the purview of the National Tay-Sachs & Allied Diseases Association (NTSAD) and include the different forms of Tay-Sachs, Sandhoff, GM-1, or Canavan. We are soliciting proposals for innovative research projects that involve basic research, translational studies or clinical studies relevant to the diseases mentioned above.  Projects may be focused on (1) technology approaches such as stem cells, molecular chaperones, substrate inhibitors, small molecule drug screening, gene therapy, novel drug delivery to the brain or on (2) other pre-clinical and clinical research needs, such as clinical outcome measures, registries, animal models, or biomarkers. This grant is made possible by Team NTSAD and the National Tay-Sachs and Allied Diseases Association.

 17) Urea Cycle Disorders (UCD): One $43,000 pilot grant available for research directed to the treatment or cure of Urea Cycle Disorders. This RFA is not restricted to a specific therapeutic modality. Preference will be given to approaches that can be leveraged across the entire spectrum of UCDs.

 

Orphan Disease Center and High-Throughput Screening Core Pilot Grant

The Orphan Disease Center, in collaboration with the University of Pennsylvania's new High-Throughput Screening Core introduced a Pilot Grant Program to highlight the expertise and service of the Core available to ODC members. Applications with a focus to utilize the Core's ability to screen either a) FDA approved/FDA-like drug libraries or b) siRNA libraries of Gene Ontology (GO) categories or user-defined gene sets to identify/validate candidate gene targets were encouraged.  Awards have been granted, and this program is now closed.

High-throughput screening core: The Penn HTSC provides the Perelman School of Medicine community with HTS resources to identify genes or organic small molecule inhibitors of signaling pathways and cellular phenotypes in models of human disease. To meet the needs of investigators, the HTSC provides consultation and assistance with assay development and high-throughput screening of chemical and genetic libraries.

For any questions regarding this grant program, please contact:
Samantha Charleston
Assistant Director
Orphan Disease Center
University of Pennsylvania
Ph: 215-573-6822
scharle@mail.med.upenn.edu