Application of an efficient drug repurposing platform to identify treatments for Cornelia De Lange Syndrome

Information

  • Research Project
  • 9041952
  • ApplicationId
    9041952
  • Core Project Number
    R43HD084025
  • Full Project Number
    1R43HD084025-01A1
  • Serial Number
    084025
  • FOA Number
    PA-14-071
  • Sub Project Id
  • Project Start Date
    9/18/2015 - 9 years ago
  • Project End Date
    7/31/2016 - 8 years ago
  • Program Officer Name
    PARISI, MELISSA
  • Budget Start Date
    9/18/2015 - 9 years ago
  • Budget End Date
    7/31/2016 - 8 years ago
  • Fiscal Year
    2015
  • Support Year
    01
  • Suffix
    A1
  • Award Notice Date
    9/18/2015 - 9 years ago

Application of an efficient drug repurposing platform to identify treatments for Cornelia De Lange Syndrome

? DESCRIPTION (provided by applicant): Cornelia de Lange Syndrome is a complex congenital malformations syndrome with many post-natal progressive medical complications. CdLS has a clear genetic cause with loss of function mutations in NIPBL accounting for over 65% of the genetically confirmed CdLS cases. The remaining cases exhibit mutations in subunits or regulators of the cohesion complex (SMC3, SMCA1, HDAC8, and RAD21). The pathophysiology of the disease is unclear and the set of symptoms are variable and complex. These many complications have prevented the identification of new treatments. Recursion Pharmaceuticals has developed a high-throughput method for modeling monogenic loss of function diseases, such as CdLS, in human cellular models. This grant expects to find a repurposed drug for treatment of CdLS by: 1. Developing siRNA induced loss of function models of CdLS mutations including NIPBL, HDAC8, and RAD21 in multiple human cell types. 2. Creating a disease phenoprint by compiling hundreds of significantly changed structural (morphological) parameters after loss of NIPBL, HDAC8, or RAD21. 3. Screen loss of function cellular lines using drug discovery platform to reveal known drugs that significantly reverse the structural disease phenotype. 4. Confirm the drug is using its known mechanism of action in CdLS rescued cellular lines Recursion has proven this platform successful with the identification of two known drugs for repurposing in another rare loss of function disease, cerebral cavernous malformation (CCM).

IC Name
EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT
  • Activity
    R43
  • Administering IC
    HD
  • Application Type
    1
  • Direct Cost Amount
  • Indirect Cost Amount
  • Total Cost
    224625
  • Sub Project Total Cost
  • ARRA Funded
    False
  • CFDA Code
    865
  • Ed Inst. Type
  • Funding ICs
    NICHD:224625\
  • Funding Mechanism
    SBIR-STTR RPGs
  • Study Section
    ZRG1
  • Study Section Name
    Special Emphasis Panel
  • Organization Name
    RECURSION PHARMACEUTICALS, LLC
  • Organization Department
  • Organization DUNS
    079240124
  • Organization City
    SALT LAKE CITY
  • Organization State
    UT
  • Organization Country
    UNITED STATES
  • Organization Zip Code
    841081201
  • Organization District
    UNITED STATES