Amyotrophic lateral sclerosis (ALS) is a relentless disease that strips away muscle control, often leading to severe disability and eventual death within a few years of diagnosis. While treatments have traditionally focused on alleviating symptoms, none have successfully halted or reversed the progression of ALS. Now, a new breakthrough promises to change that narrative by targeting the disease at its genetic roots. Using a sophisticated gene-silencing technique, researchers have developed a therapy that not only prolongs life but also significantly improves motor functions in models of ALS, offering a glimmer of hope to those affected by this devastating condition.

Led by Dr. Long-Cheng Li and Dr. Robert Place from Ractigen Therapeutics, alongside their colleagues Chunling Duan, Dr. Moorim Kang, Xiaojie Pan, Dr. Zubao Gan, Dr. Vera Huang, and Guanlin Li from Ractigen Therapeutics, a groundbreaking study has developed a promising gene-silencing therapy that extends life and improves motor functions in a mouse model of amyotrophic lateral sclerosis (ALS), a severe neurodegenerative disease. The research, focusing on a novel small interfering RNA (siRNA) modality, demonstrates significant potential to advance ALS treatment. Recently published in the journal Molecular Therapy: Nucleic Acids, this study marks a significant milestone in the fight against ALS.

“This siRNA-ACO represents a novel modality for delivery of duplex RNA to the CNS that is currently being tested in the clinic for treatment of ALS,” said Dr. Li, highlighting the innovative method of delivering therapeutic agents directly to central nervous system tissues, a critical challenge in treating neurological disorders.

The method showed that this new siRNA-ACO compound could be administered through intrathecal injection, reaching the central nervous system, where it maintained activity for up to eight weeks. This durable effect is crucial for ALS, where disease progression is rapid following diagnosis. Mice treated with the therapy not only lived longer but also showed better motor function compared to those receiving previous treatments.

“Both intracerebroventricular and intrathecal administration delays disease progression and extends animal survival in a dose-dependent manner,” explained Dr. Li, providing valuable insight into the dosage impacts and suggesting that precise control over treatment administration can optimize outcomes for patients.

Moreover, the therapy’s ability to prevent loss of motor function was particularly notable. “Treatment also prevented disease-related declines in motor function, including improvements in animal mobility, muscle strength, and coordination,” added Dr. Li. These improvements are critical markers of the therapy’s potential to significantly enhance the quality of life for ALS patients.

The implications of this study are vast, offering hope that this new treatment could soon provide relief for patients suffering from ALS. By directly targeting the genetic basis of ALS, this approach holds the promise of not just slowing but potentially halting or reversing the muscle degeneration that typifies the disease, significantly improving patient outcomes.

Dr. Li, and his colleagues are dedicated to further refining this treatment, with plans to initiate clinical trials that could establish a new frontier in gene therapy for ALS and other neurodegenerative diseases. As the scientific and medical communities look on, this research represents a major step forward in the quest to understand and combat one of the most challenging diseases of the nervous system.

Journal Reference

Chunling Duan, Moorim Kang, Xiaojie Pan, et al. “Intrathecal administration of a novel siRNA modality extends survival and improves motor function in the SOD1G93A ALS mouse model.” Molecular Therapy: Nucleic Acids (2024): DOI: https://doi.org/10.1016/j.omtn.2024.102147