Development of a VAV2 antisense oligonucleotide (ASO) treatment for ALS
Grant Award Details
Grant Type:
Grant Number:
DISC2-15114
Investigator(s):
Disease Focus:
Human Stem Cell Use:
Cell Line Generation:
Award Value:
$2,072,560
Status:
Active
Grant Application Details
Application Title:
Development of a VAV2 antisense oligonucleotide (ASO) treatment for ALS
Public Abstract:
Research Objective
Patient specific stem cells (iPSCs) to model ALS and identify a broadly acting therapeutic intervention
Impact
Heterogenous patient population, dire need for broadly acting therapeutic interventions
Major Proposed Activities
Patient specific stem cells (iPSCs) to model ALS and identify a broadly acting therapeutic intervention
Impact
Heterogenous patient population, dire need for broadly acting therapeutic interventions
Major Proposed Activities
- Compare the in vitro efficacy of up to 10 lead candidate VAV2 ASOs to rescue the survival of iNs from 30 locally and nationally recruited ALS patients
- Determine the off-target gene expression effects of the 10 lead candidate ASOs
- Select and evaluate the PK, PD, and safety of the lead VAV2 ASOs in vivo
- Quantify VAV2 suppression and pharmacokinetics for the lead candidate ASOs in hVAV2-BAC mice
- Assess glial activation and safety of the lead VAV2 ASOs in vivo
- Assess safety and tolerability of lead VAV2 ASOs in rats (Months 18-24)
Statement of Benefit to California:
California has one of the largest ALS patient populations in the nation. Successful completion will not only identify a highly promising therapeutic for a broad spectrum of ALS patients, but will utilize the immense diversity within the state to more accurately probe the nuances of disease pathogenesis and assess efficacy in a highly unique patient population.