Personalized RNA Therapy Shows Early Promise for Rare Genetic Form of ALS

A man with a rare form of amyotrophic lateral sclerosis (ALS) experienced improvements in his symptoms and continued working as a doctor one year after receiving his first dose of a personalized drug designed to target the genetic mutation causing his disease.¹

Researchers say the early findings are encouraging and could help establish a path toward treatments for neurodegenerative diseases caused by rare genetic mutations. However, they caution that it is too soon to know whether the therapy can stop ALS progression or lead to a cure.

How the personalized ALS treatment works

The man had slowly progressive ALS, also known as motor neuron disease. His condition was caused by a rare mutation that leads to the accumulation of a protein linked to the death of motor neurons.

He received an RNA-based treatment called antisense oligonucleotide therapy. Unlike conventional gene therapy, which alters a person’s genes, antisense oligonucleotides use short strands of genetic material to target RNA produced by a disease-causing gene. This can reduce the amount of harmful protein made by cells.

Steve Vucic, a neurologist and ALS researcher at the University of Sydney in Australia, described the results as an “exciting first step”. He said researchers would need to monitor participants for several more years and test the drug in more people before determining whether it can alter the course of the disease.

Fleur Garton, a neurological disease researcher at the University of Queensland in Brisbane, Australia, said similar antisense treatments could eventually benefit many people with ALS. Around 5–10% of ALS patients have a known genetic mutation. Antisense therapies appear to be safe and could potentially be developed for people with common, rare or even unique mutations, as well as for those whose disease is caused by multiple mutations.

Early signs of improvement

ALS destroys motor neurons in the brain and spinal cord. The disease can cause muscle weakness, difficulty speaking and progressive paralysis. Many people eventually need a ventilator to breathe and die from respiratory failure. There is currently no cure, treatment options remain limited, and life expectancy after diagnosis is approximately two to five years.

The patient’s disease was caused by a mutation in CHCHD10, a gene found in less than 1% of people who inherit ALS. The gene produces a protein that helps mitochondria—the cell structures responsible for generating energy—function properly. Defects in the gene can damage mitochondria and are thought to contribute to motor-neuron death.

The patient received three intraspinal doses of 50 milligrams of the drug, followed by three doses of 75 milligrams, between April 2024 and April 2025. The researchers reported no serious side effects and found no signs of cognitive decline, which can occur in people with ALS.

One year after the first dose, the patient’s blood levels of neurofilament light-chain protein had fallen to the normal baseline range. This protein is released by damaged neurons and is used as a biomarker of ALS progression. Vucic said the decline suggests that the treatment may have helped preserve neurons in the patient’s brain.

Tests of motor skills, breathing and neurological function also improved, while other measures related to breathing and cognition remained stable. Although some people with ALS experience short-term improvements without treatment, study co-author Björn Oskarsson, a neurologist at the Mayo Clinic in Jacksonville, Florida, said sustained improvement is rare.

From mutation discovery to treatment in three years

Antisense therapies targeting more common ALS mutations have taken at least a decade to develop. By contrast, the drug targeting CHCHD10 was developed in approximately three years, according to Oskarsson.

He said it was remarkable that researchers could create a drug targeting one person’s mutation, test it in animals and administer it while the patient was still alive. Further monitoring and testing will be needed to determine whether this personalized RNA therapy can provide lasting benefits for people with genetically driven ALS.