Mission

The Orphan Disease Center will develop transformative therapies using platform technologies that can be deployed across multiple rare diseases. We will emphasize disorders with substantial unmet need independent of their incidence and will strive to assure access to patients of all populations.


Impact

Each type of orphan disease affects such a small subset of the population, so the need for research and funding in this area is largely unmet. Our Center, the first of its kind, works closely with patient groups and foundations, pharma and biotech, and the academic community. We bring a unique set of programs to the table, enabling us to add value at any stage - from building the initial knowledge base to enabling therapeutic development. Through our grants, Programs of Excellence, International Patient Registries, Jump Start programs, and a number of new initiatives, the ODC seeks to drive therapeutic development for rare diseases. We help identify and fund the most promising therapeutics while also tackling obstacles present in rare disease drug development.


About Our Grantmaking

The ODC offers over 50 grant opportunities in 30+ disease areas annually to researchers across the globe, as well as within the Penn and CHOP community. Since 2011, our grant programs have funded $17.2 million in rare disease research.


Upcoming Grant Opportunities:

The Million Dollar Bike Ride Pilot Grant Program is now open. 

The Mucopolysaccharidosis Type I Grant Program is now open. 


The ODC and Loulou Foundation CDKL5 Pilot Grant Program provides a one‐year grant for $150,000.00 (total cost) to support research related to CDKL5 Deficiency Disorder (CDD). The number of awards may vary. 

Background 

CDD 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 normal 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 primarily affected. 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 seizures or improving cognitive or motor deficits.

We are seeking grant applications that progress the discovery or 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:

1) Novel therapeutic approaches for CDD, including but not limited to techniques in genome editing, RNA-based mechanisms, biologics, network modulation, and development of novel therapeutic compounds, including through small molecule repurposing. 

2) Validation of phenotypes in CDKL5 function or disease pathophysiology in cellular or animal disease models through rescue of molecular, cellular, or behavioral deficits with pharmacological or genetic / gene therapy techniques. 

     a. Phenotypic reversal in rodent models will include the use of adult (6 months of age or older) animals. 

     b. Proposals are encouraged that will identify individual CDKL5 protein isoforms (arising from alternative splicing / promoter usage, or post-translational modifications) capable of rescuing these phenotypes.

     c. Proposals are also encouraged to study phenotypic reversal in newly emerging biological domains, such as primary cilia function and microtubule dynamics, as well as potential novel functions of CDKL5 in distinct subcellular compartments (e.g., nucleus, post-synaptic density).

3) Systems biology and computational modeling approaches to provide a deeper understanding of CDKL5 function, downstream effectors, intracellular signaling, protein:protein interactors, or genetic modifiers, including regulators of CDKL5 gene expression.

4) Novel application of imaging and functional techniques to characterize the disease state of CDD pre-clinical models or in the clinical setting. A non-exclusive list of topics that would be responsive to this RFA is listed below:

     o Functional/structural MRI; diffusion tensor imaging (DTI)

     o Magnetic resonance spectroscopy (MRS)

     o EEG and stimulus-induced event-related potentials (e.g., visual; auditory; TMS-stimulated motor)

     o Proposals are encouraged which would address the impact of CDKL5 genetic / gene therapy or pharmacological interventions on these imaging and functional deficits in CDD disease models

5) Discovery and validation of CDKL5 biomarkers (molecular and functional) with the goal of their translation to the clinical setting. Of particular interest are approaches to biomarker discovery using minimally invasive testing (e.g., peripheral fluid analysis).

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. Biopharmaceutical companies are not eligible to apply; however, we will consider applications from contract research organizations who provide services that are responsive to the RFA.

LOI Due Date: LOI document is to be uploaded no later than 5pm (EST) on Friday, March 8, 2019

Please review the RFA Guidelines before submitting your LOI.

To submit your LOI, please create a Submittable account OR log in to your existing account below.


 

Orphan Disease Center