An opportunity on behalf of Target ALS and the ALS Association
With a goal to accelerate the development of novel therapeutics, two researchers have been awarded an in-kind grant, supporting the evaluation of the effect of modulating a candidate therapeutic target on the ALS phenotypes in the standardized AAV9 G4C2 (149) C9orf72 mouse model.
The initiative, a collaboration between Target ALS and the ALS Association, provides support for in vivo proof-of-concept study of efficacy of promising new therapeutics in mouse models of ALS. Target ALS will cover the costs for investigations to be conducted at JAX for a AAV9-based 149 G4C2 repeat C9orf72 mouse model originally described in Chew et al., 2019. This model replicates several features of C9orf72 ALS, including dipeptide repeats and pTDP-43, making it a relevant preclinical model for researchers whose therapeutics modulate C9orf72-related biology. Results from these studies have the potential to advance ALS drug candidates towards the clinic.
Key Objectives of the In Vivo Target Validation Program
The In Vivo Target Validation Program aims to:
- Generate high-quality data in animal models of ALS in an unbiased way based on standardized study designs and research tools.
- Break down barriers to ALS research by providing access to in-kind funding for a resource-intensive step of drug discovery
- Provide access to a preclinical model that captures dipeptide repeats, pTDP-43 pathology, and more for researchers whose therapeutics modulate C9orf72-related biology.
- Validate candidate drug targets in ALS mouse models to accelerate their progress from preclinical testing toward clinical trials.
2024 In Vivo Target Validation Grantees:
Dr Savina Apolloni
Tor Vergata University of Rome
Title: Assessing the Efficacy of Niclosamide in the C9orf72 mouse model of ALS
Summary: ALS is a severe and fatal disease that currently lacks effective treatments despite extensive global research. Niclosamide, an FDA-approved drug for over 50 years, is already known to be safe and well-tolerated in people. Due to its pleiotropic effects, re-purposing of this drug is being explored. Niclosamide has already demonstrated efficacy in slowing ALS progression, improving survival, and mitigating tissue damage in FUS and SOD1-G93A mouse models, and reduced inflammation in fibroblasts from patients with C9orf72 repeat expansions. Building on these promising findings, the objective of this project is to investigate the efficacy of niclosamide in the C9orf72 mouse model. The study will evaluate the benefit of niclosamide on disease progression through histopathological and behavioral analyses. Through this project, researchers aim to establish the viability of niclosamide as a new repurposed drug candidate for ALS.
Dr John Blackwood
Samsara Therapeutics Ltd
Title: Autophagy modulation as a potential therapeutic approach for C9orf72 ALS
Summary: Samsara Therapeutics is developing drugs that boost a process called autophagy to treat C9orf72 ALS, the most common genetic form of ALS. In earlier studies, one of Samsara’s drugs, called SAM001, showed promising results in a Prp-TDP43A315T murine model of ALS. This drug improved nerve and muscle function, helped the mice live longer, and reduced a marker of nerve damage in the blood, all without significant safety concerns. SAM001 also helped to resolve autophagy dysfunction, reduce harmful changes in neurons like TDP-43 mislocalization and dysfunction, and prevent downstream consequences in C9ORF72 ALS patient-derived motor neurons . Samsara’s goal is to further test SAM001 in C9orf72 ALS mice to see if it can reduce the damage caused by this genetic form of ALS.
About Our Review Process
At Target ALS, we hold fairness and transparency paramount in our review process. The Target ALS Independent Review Committee (IRC) makes all research funding decisions without involvement from the organization’s staff or leadership, ensuring every application receives a fair evaluation. The IRC is comprised of experts across scientific disciplines from both industry and academia, reflecting the evolving nature of ALS research. To avoid any possible conflicts of interest, no member of the IRC can apply for or receive Target ALS funding for their own work. Members on the IRC abide by a comprehensive conflict of interest policy and are all under confidentiality agreements. For more detailed information about our grants and the application process, please visit our In Vivo Target Validation Page.
