Summary
A man with slowly progressing ALS caused by a rare CHCHD10 mutation showed improved motor-function scores and a biomarker associated with nerve damage returned to the normal reference range one year after receiving a mutation-targeted antisense oligonucleotide treatment.
A man with a rare, slowly progressing form of amyotrophic lateral sclerosis (ALS) showed improved symptoms one year after receiving an RNA drug designed for the mutation causing his disease. He became the first person to receive this treatment, which was developed to target a mutation in the CHCHD10 gene.
The early result comes from a report of one treated participant. The man continued working as a physician, and the researchers reported no serious negative side effects during the treatment period. Longer follow-up and treatment in more people will be needed to determine whether the approach can slow disease progression or provide lasting benefit.
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What the treatment targets
ALS causes motor neurons in the brain and spinal cord to die. These nerve cells control movement, so their loss can lead to muscle weakness, difficulty speaking and progressive paralysis. Breathing muscles can eventually be affected, and respiratory failure is a common cause of death. Average life expectancy after diagnosis is about two to five years, according to the report.
The participant’s disease is linked to a rare CHCHD10 mutation found in fewer than 1% of people who inherit ALS. The gene encodes a protein involved in the function of mitochondria, the structures that generate energy for cells. Defects in the gene can damage mitochondrial function and are thought to contribute to motor-neuron death.
The treatment is an antisense oligonucleotide, or ASO. These drugs use short strands of genetic material to bind to RNA produced from a disease-associated gene and reduce the amount of the corresponding protein. This differs from conventional gene therapy, which aims to alter a person’s genes.
The man received three 50-milligram doses injected into his spine, followed by three 75-milligram doses, between April 2024 and April 2025.
Changes reported after treatment
One year after the first dose, the man’s blood concentration of neurofilament light chain had fallen to the normal reference range. Neurofilament light chain is released by damaged neurons and is used as a biomarker of ALS progression. Neurologist Steve Vucic said the reduction suggests that neurons in the man’s brain may have been preserved.
The participant’s score on a test covering motor skills, breathing and neurological function also improved. Separate measures of breathing and cognition remained stable, and he showed no signs of cognitive decline, which can occur in ALS.
The researchers noted that some people with ALS experience short-term symptom improvements without treatment. Björn Oskarrson, a neurologist and co-author of the report, said sustained improvement without treatment is rare. The result is therefore encouraging, while still representing an early observation in a single person.
Why mutation-specific RNA drugs matter
Around 5–10% of people with ALS have a known genetic mutation. Existing antisense treatments have been developed for some more common ALS mutations, but the report says those programmes took at least a decade to develop. The CHCHD10-targeted drug was developed in three years, according to Oskarrson.
That shorter development path could make it more practical to create treatments for people with rare or even unique mutations. Fleur Garton, a neurological disease researcher, said similar therapies could also be developed for people whose disease involves common mutations, rare mutations or multiple mutations.
The next key evidence will come from continued monitoring of the participant and treatment of additional people. Vucic said another two or three years of follow-up, together with testing in more patients, will be needed to establish whether the therapy can change the course of the disease rather than only coincide with an early improvement.