Early findings show stable breathing, physical function, and a reduction in nerve injury biomarkers.
RT’s Three Key Takeaways:
- Individualized Therapy Approach: Mayo Clinic researchers evaluated an experimental antisense oligonucleotide developed for a single patient with a rare genetic form of amyotrophic lateral sclerosis linked to a mutation in the CHCHD10 gene.
- Stable Respiratory and Motor Metrics: Following six spinal fluid injections of the experimental drug, the patient showed stable to modestly improved breathing, physical function, and cognition, alongside a decline of up to 50% in neurofilament light levels.
- Precision Medicine Framework: The single-patient trial forms part of Mayo Clinic’s N-of-1 Therapeutics Program, aiming to establish safety, translation, and development protocols that could inform genetic treatments for other neuromuscular and neurodegenerative conditions.
Mayo Clinic researchers reported early findings from an experimental treatment designed for a single patient with a rare genetic form of amyotrophic lateral sclerosis (ALS), according to a study published in Med.
The investigation focused on an individual with a mutation in the CHCHD10 gene, which damages motor neurons and connects to abnormalities in TDP-43, a protein closely tied to ALS progression. To address the mutation, Mayo Clinic teamed with the nonprofit n-Lorem Foundation to evaluate more than 320 antisense oligonucleotides (ASOs)—short synthetic strands of genetic material designed to bind to RNA and reduce harmful protein production—before selecting a lead candidate.
“I didn’t think I would see this kind of research in my lifetime — identifying a disease-causing mutation, developing an experimental therapy and delivering it to a patient,” said Björn Oskarsson, MD, a Mayo Clinic neurologist and senior author of the study. “It speaks to the power of science and how far genetically targeted treatments have come.”
Biomarker Reductions and Functional Stability
The single-patient report reviewed the outcomes of six initial doses of the investigational ASO administered via injections into the fluid surrounding the spinal cord. According to the study, the treatment was well tolerated, and blood levels of neurofilament light, a biomarker indicative of nerve-cell injury, dropped by as much as 50%.
In addition, clinical evaluations tracking breathing, cognitive abilities, and physical function demonstrated stability or modest improvement throughout the administration period.
“The quick response in neurofilament light was very encouraging,” said Dr Oskarsson, emphasizing that stabilization represents a clinically meaningful result in a progressive, degenerative disease like ALS.
Using cellular samples gathered before and during drug delivery, investigators are continuing to assess alterations in TDP-43, mitochondrial function, and overall gene activity to observe how suppressing the target gene alters disease mechanics.
Developing a Model for Rare Genetic Diseases
The experimental intervention remains an active research protocol and does not constitute standard clinical healthcare practice, according to the researchers. Dr Oskarsson estimated that genetic mutations account for roughly 50% of ALS cases, though only a portion of those patients possess genetic profiles compatible with ASO platforms, while others may require tools like gene editing.
The study is part of Mayo Clinic’s N-of-1 Therapeutics Program, which explores personalized genetic drug development, monitoring protocols, and clinical assessment standards for ultrarare disorders.
“Cases like this are how we get started,” said Margot Cousin, PhD, director of the N-of-1 Therapeutics Program and lead author of the study. “They help us build the scientific, clinical, translational and regulatory framework to do this rigorously and equitably. As we learn how to scale these approaches, the impact could reach far beyond ultrarare disease.”
