AAV Gene Therapy Study Shows Promise in Delaying ALS Onset in Mice

Piscataway, NJ – November 14, 2025 — Researchers have published a groundbreaking preclinical study that unveils a potential new therapeutic strategy for Amyotrophic Lateral Sclerosis (ALS). The innovative gene therapy technique, detailed in the journal Gene Therapy, utilizes adeno-associated virus (AAV) vectors to deliver therapeutic factors directly to muscle tissues, resulting in a significant delay in disease onset in the SOD1^G93A ALS mice model. The current study highlights the promise of using AAV vectors to specifically target muscle tissues, which has not only shown safety but also a noteworthy efficacy in delaying ALS progression.

Targeted Muscle Delivery: A New AAV-Based ALS Strategy

The study redefines potential therapeutic mechanisms by shifting focus from the central nervous system to peripheral tissues, specifically muscle, using the AAV platform. The AAV vectors were designed to carry the genes for two key proteins:

• Brain-Derived Neurotrophic Factor (BDNF): This neurotrophic factor is critical for motor neuron survival. Augmenting BDNF levels in the muscle via the AAV vector is believed to exert a systemic, neuroprotective effect.
• Growth Arrest-Specific Protein 6 (GAS6): This protein promotes cell survival and modulates the immune response. GAS6 delivered by the AAV appears to modify the inflammatory environment, benefiting motor neurons.

The methodology involved administering the AAV vectors carrying the BDNF and GAS6 genes directly into the muscles. This targeted AAV approach maximized therapeutic potential while minimizing systemic exposure and associated side effects.

AAV Success: Preservation of Motor Neurons

The results from the preclinical model using the AAV delivery system were highly encouraging. Over the evaluation period, researchers observed a remarkable preservation of motor neuron populations and overall maintenance of muscle integrity.

The preservation seen with this AAV intervention directly correlates with the functional outcomes in ALS patients. The findings support the idea that interventions directed at skeletal muscle using AAV can result in widespread benefits across the nervous system, furthering the understanding of muscle-secreted factors in neuronal health.

AAV Outlook for Clinical Translation

While the findings provide a strong rationale for advancing these concepts, the long-term safety and efficacy of the AAV-mediated gene delivery must be thoroughly assessed before clinical translation can occur.

Should this dual-factor AAV approach prove successful, it could mark a paradigm shift in ALS management. Furthermore, the principles of AAV gene delivery employed could be adapted to various other neurodegenerative diseases.