The Orphan Disease Center (ODC) at the University of Pennsylvania and the Loulou Foundation are pleased to announce the 2019 Pilot Grant Program for CDKL5 Deficiency Disorder (CDD). CDD is a monogenic disorder characterized by treatment-resistant epilepsy and severe cognitive and motor disability. The Loulou Foundation and the ODC will provide a one-year grant for $150,000.00 (total cost) to support research related to CDD therapeutic development – number of awards may vary. The anticipated funding period for the awarded grants will be from May 1, 2019, to April 30, 2020.

This funding opportunity is applicable to those holding a faculty-level appointment. All applicants must first submit a letter of Interest (LOI) to be reviewed for consideration of a full application submission. LOIs are due no later than Friday, March 8, 2019 at 5pm (EST). LOIs can be uploaded on the website.

We are seeking grant applications that progress the discovery or development of treatments or cures for CDD. 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.

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

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:

• Functional/structural MRI; diffusion tensor imaging (DTI)
• Magnetic resonance spectroscopy (MRS)
• EEG and stimulus-induced event-related potentials (e.g., visual; auditory; TMS-stimulated motor)
• 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).