Development of AS-241, an UNC13A Targeting Antisense Oligonucleotide (ASO) Treatment for ALS, for IND-enabling Studies

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Grant Award Details

Grant Number:
TRAN1-16013
Investigator(s):
Institution:
Type:
PI

Award Value:
$4,012,325
Status:
Pre-Active

Grant Application Details

Application Title:

Development of AS-241, an UNC13A Targeting Antisense Oligonucleotide (ASO) Treatment for ALS, for IND-enabling Studies

Public Abstract:
Translational Candidate

AS-241, an antisense oligonucleotide

Area of Impact

Amyotrophic Lateral Sclerosis

Mechanism of Action

AS-241 targets the cryptic exon (CE) of UNC13A and suppresses CE inclusion during RNA splicing, inhibits nonsense-mediated decay, and increases full length mRNA and protein levels

Unmet Medical Need

To date, therapeutic options for ALS have been limited, and disease-modifying drugs remain to be developed. Current FDA approved drugs Riluzole and edaravone are not effective. Tofersen only targets 2% of ALS patients with SOD1 mutation.

Project Objective

Conduct a pre-IND meeting

Major Proposed Activities

  • Develop manufacturing schema of AS-241 and manufacture a non GMP batch of 200g
  • Conduct pharmacological studies in rodents and NHP
  • Conduct pilot safety and dose range finding studies in rodents and NHP
Statement of Benefit to California:
Being one of the most popular States, California has many ALS patients. We have met many of them during the annual ALS walk. Most of them suffer ALS from unknown causes with only a small percentage have known genetic mutation. AS-241 is designed to help more than 97% ALS patients (the percentage of patients with TDP-43 pathology). Our preliminary data showed that it is safe and likely to be effective. This proposal would help us to conduct a successful IND meeting with the FDA.