DSF Special RFA: Broader Genetic Impacts on Phenotype in Dravet Syndrome
The Dravet Syndrome Foundation (DSF) is issuing a special request for grant applications proposing research projects that will deepen our understanding of genetic impacts on the diverse phenotypic outcomes of individuals with Dravet syndrome.
Application Due Date: September 8, 2023
Award Budget: up to $1M distributed over 3 years (beginning in January 2024)
Purpose and Objectives: The clinical presentation of Dravet syndrome is well-defined, characterized by intractable seizures beginning in infancy as well as a range of comorbidities that include intellectual disability, behavior issues, movement and gait disorders, language and speech difficulties, sleep disruptions, and dysautonomia. However, the manifestation and severity of these clinical symptoms, as well as response to medical interventions, can differ among patients. Heterozygous loss-of-function variants in SCN1A are found in the majority (>80%) of patients diagnosed with Dravet syndrome. Causal mutations are varied (missense, nonsense, insertions and deletions) and have been identified in every exon of SCN1A. Research efforts have not been successful in uncovering clear phenotype-genotype correlations based on SCN1A variants alone. Environmental factors likely impact patient outcomes, but studies in animal models and families with inherited SCN1A mutations suggest the interplay of other genetic factors. A deeper understanding of these genetic interactions could contribute to our understanding of disease etiology, and potentially provide meaningful clinical insights.
Project Requirements: DSF will consider budget proposals of up to $1,000,000 (including direct and indirect costs) over a 3 year timeframe for projects that propose to address the topic of broader genetic impacts on diverse phenotypic outcomes in human subjects with Dravet syndrome.
Projects are expected to generate substantial datasets from human samples using whole genome sequencing and/or other multi-omic approaches.
Anticipated results should aim to uncover novel insights into disease that have the potential to impact clinical care and spur new lines of research.
Projects should include plans for representation from diverse populations in the study cohort including patients from diverse geographical, racial and ethnic, and socioeconomic backgrounds.
Proposals must include detailed plans for data sharing to ensure that resources developed within the project are accessible for future discovery.
DSF encourages researchers to incorporate plans for biospecimen banking, that, similar to the data, could be used in future collaborative efforts.
Review of Applications:
Grant applications will be scored principally on novelty of the hypotheses, innovative approaches with a direct relevance and application to Dravet syndrome, scientific quality, rigor of the overall approach and analytic methods, strength of expertise, and likelihood of success. Applications undergo a rigorous NIH-style scientific review process and final decisions are made by the DSF Board of Directors, ensuring projects funded by DSF meet high scientific standards and align with the most pressing needs of the patient community. Research Grant Awardees are required to give updates on their work throughout the grant cycle and present their findings at DSF’s annual Research Roundtable meeting.
Applicants should hold an MD, PhD, DO, or equivalent degree and should be affiliated with a research or academic institution (excluding for-profit companies). Applicants may be US- or foreign-based, must be established in their field, and should be in good standing with their respective institution. Collaborative, multi-investigator and/or multi-center applications are highly encouraged.
Tags: Dravet Syndrome, SCN1A, Genetics
Mary Anne Meskis