The Collaborative Center for XDP invites applications for funding.

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 caused by a transposable element. CCXDP is now seeking applications for its 2020 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 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.

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 

View a complete list of available resources.

Research Objectives for the 2020 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:

  • 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
  • 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 of gene therapy strategies, including methods for in vivo genome editing of pathogenic sequences and/or delivery of therapeutic factors
  • Studies of potential RNA-based mechanisms of toxicity in XDP cells, including consequences of intron retention, SVA-derived RNAs, effects on RNA binding proteins and splicing factors, and/or RAN translation
  • Proteomic profiling of XDP-related cell/animal models and/or post-mortem brain tissue
  • Development and application of novel iPSC-based models, including organoids
  • Comparative analyses to identify cellular mechanisms that may be shared by XDP and other neurodegenerative diseases

View a complete list of ongoing and completed CCXDP projects.

Application Instructions

Applications are due by 5:00 pm Eastern Time (US) on Friday, January 15, 2021.

To apply, you will need to submit:

Download instructions

Additional Application Resources

For any additional questions, please contact Dr. Amy Alessi, CCXDP Program Director, at aalessi@partners.org.