A year after his treatment began, a man with a rare inherited form of ALS was still working as a physician. Nature reported that he is the first patient given a drug engineered around the specific mutation that causes his illness. Researchers call the early results exciting.
The details come from a paper in the journal Med by a team at Mayo Clinic and Orlando Health. In the CHCHD10 gene, the patient has a variant named p.Arg15Leu. Trouble first showed up in 2020, in his right shoulder, and the genetic diagnosis came in 2021. CHCHD10 helps make a protein found in mitochondria, the parts of a cell that produce energy, and faulty versions are linked to ALS. Fewer than 1% of people with hereditary ALS have this mutation, so a conventional trial with thousands of participants would be hard to run.
A drug built for one person
The team took a different route, a one-patient treatment sometimes called an N-of-1 study. They screened 320 candidate molecules before choosing the experimental medicine nL-CHCHD-001. It is an antisense oligonucleotide, a short strand of lab-made genetic material that binds to a chosen RNA and lowers the amount of one protein the cell makes. It does not rewrite his DNA. Because its action fades, repeated doses may be needed.
Across twelve months, starting in April 2024, he received six doses, injected into the fluid around the spinal cord. No serious side effects appeared. Headache and fatigue were reported and rated mild to moderate.
What changed
Doctors tracked several measures over 12 months. Neurofilament light, a protein that leaks from damaged nerve cells into the blood, fell by about 50% and moved into the laboratory’s normal range. His score on a standard ALS functional scale, which covers everyday tasks from speech and swallowing to walking and breathing, rose from 33 to 36. His predicted vital capacity, a measure tied to breathing, climbed from 48% to 55%. In ALS, scores normally slide downward, so a rise is notable.
“We have shown that it is possible to develop a personalized ASO therapy for CHCHD10-related ALS,” the researchers said.
The caution that comes with it
The study had a single participant and no blinding. It cannot prove the drug caused the gains, or that it would help anyone else. A biomarker is also not the same thing as living longer. The treatment is experimental and has no regulatory approval.
There is precedent for the approach. In 2023 the FDA granted accelerated approval to tofersen, another antisense drug, for adults whose ALS is caused by SOD1 mutations. That decision rested partly on a drop in the same nerve-damage marker.
For families living with rare inherited forms of ALS, the encouraging part is that a medicine can now be designed around a single mutation. Early findings like these are a first step, not a treatment on the shelf. Patients and relatives should talk to their doctor before drawing any conclusions about their own care.
Sources
- First for RNA therapy: man with rare motor-neuron disease improves after treatment (Nature)
- Personalized RNA Therapy Shows Promise for Rare ALS (Medindia, reporting the Med paper)
- Mayo Clinic develops personalized RNA therapy that improves ALS motor scores (DongA Science)
