First ALS patient shows sustained improvement after custom RNA therapy
A man with rare amyotrophic lateral sclerosis (ALS) experienced improved symptoms and maintained his career as a physician one year after receiving the first antisense oligonucleotide therapy targeting his specific genetic mutation. The treatment, delivered via spinal injection, reduced biomarkers of neuron damage to normal levels without serious side effects. Researchers describe this as a foundational step for treating neurodegenerative diseases caused by rare mutations, noting that the drug was developed in just three years compared to the decade-long timelines for common mutations.
Key points
- The patient has a slowly progressing form of ALS caused by a rare mutation in the CHCHD10 gene, which affects mitochondrial function and leads to motor neuron death.
- He received six doses of an antisense oligonucleotide drug between April 2024 and April 2025, starting with 50-milligram doses and increasing to 75-milligram doses.
- One year post-treatment, his neurofilament light chain protein levels, a biomarker for ALS progression, returned to the normal reference range.
- Scores for motor skills, breathing, and neurological function improved, while cognitive function remained stable with no signs of decline.
- The therapy targets RNA produced by the gene to reduce harmful protein buildup, differing from traditional gene therapy that alters DNA.
Background
This development follows recent advancements in RNA-based therapies for other genetic conditions. In August 2026, researchers at the University of Toronto reported on inhalable tRNA therapies that reversed defects in cystic fibrosis models by bypassing stop signals. Additionally, earlier in 2026, studies explored converting brain support cells into neurons using polymer gels for Alzheimer’s research, highlighting a broader trend in using targeted molecular interventions to address neurodegenerative and genetic disorders.
Why it matters
This case demonstrates the feasibility of rapid, patient-specific drug development for ultra-rare genetic diseases. By targeting RNA rather than altering genes, this approach offers a safer and faster pathway to treatment for individuals with unique mutations, potentially extending the benefits of gene-targeting therapies to the 5-10% of ALS patients with known genetic causes.
What to watch
Researchers plan to monitor the patient for another two to three years to determine if the treatment halts disease progression or acts as a cure. Future trials will test the drug in more individuals to assess long-term efficacy and safety, aiming to establish a broader framework for treating rare neurodegenerative conditions.
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