This program is seeking grant applications that progress the discovery or development of treatments and/or cures for CDKL5 Deficiency. The Foundation recognizes that gaps still remain in the understanding of the biology of CDKL5 and its role in neurological development and function, applications that address such gaps in basic science are welcome, provided that 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, novel cell-based therapeutics, network modulation, and development of novel therapeutic compounds, including through small molecule repurposing or screening against validated phenotypes in human cellular systems. Also encouraged are novel delivery systems for gene therapy and genome editing cargoes.
2. Establishment of the link between molecular function of CDKL5 and disease pathophysiology in cellular or animal disease models through rescue or modulation of molecular, cellular, or behavioral deficits via pharmacological or genetic / gene therapy interventions.
• Phenotypic reversal in rodent models will include the use of adult (e.g., 6 months of age or older) animals, to address effects over the natural history of the phenotype in the animal model.
• Proposals are also encouraged to study phenotypic reversal in newly emerging biological domains, such as primary cilia function and microtubule dynamics, and peripheral organ systems, as well as potential novel functions of CDKL5 in distinct subcellular compartments (e.g., nucleus, post-synaptic density; nucleic acid binding), provided that a link to pathophysiology can be established or hypothesized.
3. Systems biology and computational modeling approaches to provide a deeper understanding of CDKL5 function, downstream effectors, intracellular signaling, protein: protein interactor networks, or genetic modifiers from model organisms and human cellular models, including regulators of CDKL5 gene expression, or the expression of CDKL family members.
4. Discovery and validation of CDKL5 biomarkers (molecular and functional) and clinical outcome development with the goal of translation to the clinical setting.
• Molecular biomarker discovery and validation of candidate biomarkers in patient and model system fluids such as plasma and CSF.
• 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 potential reversal of these imaging and functional deficits by CDKL5 genetic / gene therapy or pharmacological interventions in CDD disease models, and potential mechanisms of CDKL5 function in these systems.
• Clinical outcome development for CDD, including in domains such as visual function, fine motor/hand use skills, etc.
  

Allowable direct costs:

• Salary for PI
• Salary/stipend and related benefits for graduate student/postdoctoral fellow/technical support
• Travel (up to $1500)
• Laboratory supplies and other research expenses

For information about grant review criteria, see https://static1.squarespace.com/static/5fbd2cd686a75170665fde3e/t/63cfec6073f30e4784374fc6/1674570848469/2023+CDKL5+RFA.pdf#page=5