The Collaborative Center for XDP funds research through a competitive grants program. The Center has issued a new request for proposals with an application deadline of October 27, 2021.
The Collaborative Center for X-Linked Dystonia-Parkinsonism (CCXDP) supports an international consortium of scientists, clinicians, and patient advocates working together to advance research and treatments for X-Linked Dystonia-Parkinsonism (XDP), a debilitating neurodegenerative disease caused by a transposable element. CCXDP periodically issues requests for proposals for the Research Funding Program. Three grant mechanisms are offered:
- Investigator Awards: 2 years, up to $250,000/year in direct costs
- Exploratory Pilot Grants: 1 year, up to $100,000 in direct costs
- Postdoctoral fellowships: 2 years, $75,000/year in direct costs
In addition to the amounts listed above, awards will provide 10% indirect costs to recipient institutions.
XDP is a neurodegenerative disorder endemic to the Philippines. CCXDP-funded research studies have shown that XDP is most likely caused by a disease-specific SINE-VNTR-Alu (SVA)-type retrotransposon insertion in an intron of the human TAF1 gene. The SVA contains a hexameric sequence (CCCTCT)n, the length of which is polymorphic among patients and inversely correlated to age of disease onset. The insertion results in aberrant TAF1 mRNA splicing and partial intron retention which decreases levels of the full-length transcript. The neuropathology of XDP has not yet been fully defined, but previous studies have reported a progressive loss of striatal medium spiny neurons in the brains of individuals with XDP.
CCXDP has generated biospecimens and reagents which are available for research studies, including:
- DNA from XDP patients and unaffected relatives
- Fibroblasts, lymphoblasts, and induced pluripotent stem cells (iPSCs) from XDP patients and unaffected relatives
- Post-mortem human brain tissue from XDP patients
- Novel TAF1 antibodies
View list of projects
Research Objectives for the 2021 Funding Program
CCXDP welcomes applications from investigators in all disciplines proposing bold and rigorous approaches to the study of XDP. We encourage proposals involving collaborative studies, which can include investigators at different institutions, as well as ones which leverage existing resources. Areas of particular interest include, but are not limited to:
- Screening projects that develop models and/or assays to seek compounds that modulate XDP-related phenotypes, with particular emphasis on opportunities for drug repurposing
- Development and application of novel XDP model systems, including strategies for (a) studying SVA knock- in and/or TAF1 knockout in animals; and (b) creating 2D and 3D culture models using XDP-specific induced pluripotent stem cells
- Studies of post-mortem brain tissue to elucidate potential disease mechanisms
- Development of novel CRISPR-based genome editing strategies for therapeutic manipulation of the disease-specific SVA insertion
- Neuroimaging to probe markers of disease progression in XDP individuals
- Studies of the XDP-specific SVA element, including potential regulation by host cell factors and effects on chromatin, RNA transcription, and/or DNA replication dynamics
- Comparative analyses to identify cellular mechanisms that may be shared by XDP and other neurodegenerative diseases
September 20, 2021: Letters of intent due by 5:00 pm Eastern Time. Abstracts of proposed research may be emailed to firstname.lastname@example.org.
October 27, 2021: Full applications due by 5:00 pm Eastern Time to email@example.com.
February, 2022: Funding decisions announced.
May, 2022: Anticipated project start dates.