Purpose

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 endemic to the Philippines. CCXDP is now seeking applications for its 2024-25 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.

Background

XDP is a neurodegenerative disorder affecting individuals with maternal ancestry to the island of Panay in 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.

 

Research Objectives for the 2024-2025 Funding Program

CCXDP welcomes applications from investigators in all disciplines proposing bold and rigorous approaches to the study of XDP. We particularly encourage proposals that apply insights gained from studies of other neurodegenerative disorders to investigations of potential disease mechanisms in XDP.  Collaborative projects, which may include teams at different institutions, are permitted, and applicants are encouraged to review the list of cell and tissue resources available from CCXDP.  Areas of particular interest include, but are not limited to:

•      The role of glial cells in XDP pathogenesis, including the potential contribution of   neuroinflammation.

•      Cellular mechanisms underlying neuronal cell death in XDP, including the characterization of   candidate targets and/or pathways that may be common among other neurodegenerative   diseases.

•      Molecular studies of the XDP-specific SVA element, including but not limited to potential regulation by host cell factors, RNA transcription, and/or DNA replication dynamics.

•      Screening projects that develop models and/or assays to seek compounds that modulate XDP-related phenotypes, with emphasis on opportunities for drug repurposing.

•      Projects that leverage machine learning/artificial intelligence (AI) to identify and analyze   phenotypes in XDP model systems.

•      Functional analyses of TAF1 protein, including but not limited to mechanisms of gene regulation  and/or interactions with partner proteins, with specific emphasis on how these  functions may be affected in XDP cells.

 

Available Resources

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

For a complete list of available resources and details about acquiring reagents, please see:

https://ccxdp.org/our-research/resources/

 

Application Timeline

September 16, 2024:             Letters of intent due by 5 pm EST.

November 11, 2024:              Full applications due by 5 pm EST

May 2025:                               Funding decisions announced.

July 2025:                                Anticipated project start date.

 

Application Instructions

Step 1:  Complete the initial inquiry form below. Once submitted, you will be sent a unique survey link to fill out your LOI, or you may complete it here as well if ready.

Step 2: Submit Letter of intent (LOI) using your emailed survey link by Sept 16th.

  Submission of an LOI is required.  Each will be reviewed and an invitation to apply will be sent if approved.

  Step 3: Should your LOI be approved, you will receive a second link to fill out the application form.          Submit full grant applications portal by November 11th.

To preview application instructions and required documents, see linked PDF below.

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