SORT1:PGRN blocking antibodies for Frontotemporal dementia

Information

  • Research Project
  • 9322703
  • ApplicationId
    9322703
  • Core Project Number
    R44AG050363
  • Full Project Number
    4R44AG050363-02
  • Serial Number
    050363
  • FOA Number
    PA-14-071
  • Sub Project Id
  • Project Start Date
    9/30/2016 - 7 years ago
  • Project End Date
    8/31/2017 - 6 years ago
  • Program Officer Name
    REFOLO, LORENZO
  • Budget Start Date
    9/30/2016 - 7 years ago
  • Budget End Date
    8/31/2017 - 6 years ago
  • Fiscal Year
    2016
  • Support Year
    02
  • Suffix
  • Award Notice Date
    9/17/2016 - 7 years ago
Organizations

SORT1:PGRN blocking antibodies for Frontotemporal dementia

? DESCRIPTION (provided by applicant): SORT1 blocking antibodies for Alzheimer's disease and Frontotemporal dementia Alector's objective is to develop therapeutic antibodies against the receptor Sortilin1 (SORT1) for the treatment of the devastating neurological disorders Frontotemporal Dementia (FTD) and Alzheimer's Disease (AD). FTD is a progressive disease that causes incapacitating changes in behavior, language, movement and cognition, and is the most common of the pre-senile dementias, affecting ~50,000-60,000 people in the US. AD is the most common cause of dementia, which shares many pathological and phenotypic features with FTD. As AD affects an estimated 5M Americans, with the numbers increasing steadily, the disease represents a major public health issue. There is no effective treatment for FTD, which is typically diagnosed 3-4 years after symptom onset, with a median survival of 6-11 years. Furthermore, there are no available treatments that halt progression of AD. Ultimately, patients with FTD or AD will require round-the-clock medical care. Progranulin (PGRN) is a neurotrophin that has been identified as a risk factor for neurodegenerative diseases. PGRN haploinsufficiency is causal for 10% of all FTD cases, while other alleles are associated with the development of late onset AD. SORT1 is a transmembrane receptor that controls the extracellular level of PGRN by binding it at the cell surface and rapidly internalizing it for lysosomal degradation, while it is dispensable for PGRN signaling. We propose to generate a therapeutic that can elevate extracellular levels of PGRN by developing antibodies that bind SORT1, block the interaction with PGRN, and thus functionally elevate PGRN levels in vitro and in vivo. Effective lead antibodies will be optimized for affinity and other characteristics and advanced for confirmatory and preclinical testing as development candidates. Both the dataset and SORT1 antibodies produced in this project would allow us to secure the additional funds necessary for advancing the candidate to preclinical testing, to IND submission, and to the clinic. Trials with a SORT1 antibody in patients with PGRN mutations would conclusively determine whether therapeutic PGRN elevation could provide meaningful clinical benefit in FTD and AD patients as hypothesized.

IC Name
NATIONAL INSTITUTE ON AGING
  • Activity
    R44
  • Administering IC
    AG
  • Application Type
    4
  • Direct Cost Amount
  • Indirect Cost Amount
  • Total Cost
    1294191
  • Sub Project Total Cost
  • ARRA Funded
    False
  • CFDA Code
    866
  • Ed Inst. Type
  • Funding ICs
    NIA:1294191\
  • Funding Mechanism
    SBIR-STTR RPGs
  • Study Section
    ZRG1
  • Study Section Name
    Special Emphasis Panel
  • Organization Name
    ALECTOR, LLC
  • Organization Department
  • Organization DUNS
    079251676
  • Organization City
    SAN FRANCISCO
  • Organization State
    CA
  • Organization Country
    UNITED STATES
  • Organization Zip Code
    941073007
  • Organization District
    UNITED STATES