Custom RNA drug improves rare ALS in first personalized case

Overview

Updated Sep 21

A physician with a rare inherited form of amyotrophic lateral sclerosis (ALS) received a drug built around his own gene mutation, the first therapy designed for this genetic form of the disease. A year after his first dose, his neuron-damage biomarker fell into the normal range and he kept practicing medicine.

The drug, an antisense oligonucleotide, took three years to develop and cost about $1.2 million, paid by the nonprofit n-Lorem Foundation. About 10 people with the same gene fault are now being treated using that drug as a starting point, and a second single-patient trial is registered.

Why it matters

A drug built around one patient's mutation slowed his ALS, and the same approach now reaches about 10 more people with rare genetic disease.

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Key Indicators

~50%

Plasma neurofilament light reduction

Neuron-damage biomarker dropped from a mildly elevated baseline into the normal reference range.

33 to 36

ALSFRS-R score improvement

Motor function, breathing, and neurological function test rose by three points.

48% to 55%

Vital capacity change

Breathing capacity rose seven percentage points of predicted value.

3 years

Development timeline

From mutation identification to first dose, versus a decade or more for earlier antisense therapies.

Patients now treated

People with CHCHD10 mutations receiving the drug or versions of it, per n-Lorem Foundation.

$1.2M

Cost to develop the first drug

n-Lorem paid to design and manufacture the drug. Adapting it for others with the same mutation is faster and cheaper.

Voices

Curated perspectives — historical figures and your fellow readers.

People Involved

Björn Oskarrson

Neurologist at Mayo Clinic in Jacksonville, Florida

Study co-author, reported results September 2026

Steve Vucic

Neurologist and ALS researcher at University of Sydney

External expert commenting on the results

Fleur Garton

Neurological disease researcher at University of Queensland

External expert commenting on implications for broader ASO treatment

Unnamed trial participant (practicing physician)

First patient to receive nL-CHCHD-001

Alive and working as a physician at 12-month follow-up; NBC News identified him as Parekh

Stanley Crooke

n-Lorem Foundation official

Quoted in NBC News coverage of the program's expansion

Organizations Involved

n-Lorem Foundation

Nonprofit foundation

Developed and supplied nL-CHCHD-001; now treating about 10 people

Develops patient-specific antisense oligonucleotides for people with ultra-rare genetic diseases.

Mayo Clinic

Academic medical center

Conducted the N-of-1 clinical study

Academic medical center that ran the single-patient trial in Jacksonville, Florida.

Med

Peer-reviewed medical journal

Published the study September 2026

Cell Press journal that published the single-participant trial report.

Timeline

April 2024 September 2026

4 events Latest: September 18th, 2026 · 2 months ago

Tap a bar to jump to that date

September 2026
Results published
Latest Publication

Study reports biomarker normalization and stable or improved clinical measures.
September 18th, 2026
March 2026
Second CHCHD10 single-patient trial planned
Clinical

n-Lorem Foundation and Mayo Clinic registered a second N-of-1 antisense trial (NCT07423494) for another participant with CHCHD10-related ALS. ClinicalTrials.gov lists a March 2026 start; as of September 2026 it is not yet recruiting, with completion planned for March 2027.
March 1st, 2026
April 2025
Treatment course completes
Clinical

Sixth and final dose administered after a 12-month dosing window; follow-up phase begins.
April 16th, 2025
April 2024
Treatment begins
Clinical

First of six intrathecal doses of nL-CHCHD-001 delivered into the spine. ClinicalTrials.gov records the study start as April 16, 2024.
April 16th, 2024

Scenarios

CHCHD10 therapy expands to a small trial

Likely Resolves by End of 2028

Discussed by: Björn Oskarrson and the Med study authors

The drug is already built and shown safe in one person. Enrolling additional patients with CHCHD10 mutations would test whether the benefit extends beyond this individual. n-Lorem has the platform to supply the drug; the open question is patient recruitment, since the mutation is ultra-rare.

N-of-1 platform reaches other rare ALS mutations

Possible Resolves by End of 2029

Discussed by: Fleur Garton in comments to Nature

Garton said the approach could work for people with common, rare, or even unique ALS mutations. If the three-year development pipeline becomes standard, other groups could replicate it for different genes. Success depends on the platform's cost, speed, and regulatory acceptance across institutions.

Two-to-three-year follow-up shows durable benefit

Uncertain Resolves by Q3 2029

Discussed by: Steve Vucic in comments to Nature

Vucic said it is too early to know whether the treatment can stop progression or cure. The participant needs another two to three years of monitoring, along with tests in more patients. If his clinical measures remain stable or improve at that mark, the drug's benefit would look durable rather than temporary.

Second CHCHD10 patient shows similar benefit

Likely Resolves by Q1 2027

Discussed by: n-Lorem Foundation (Crooke) and NBC News reporting

n-Lorem says about 10 people are being treated using the first drug as a starting point, and a second formal N-of-1 trial (nL18576) is registered for another CHCHD10 patient. If that participant also shows a neurofilament-light drop into the normal range, the case for patient-specific drugs for ultra-rare ALS mutations strengthens.

Historical Context

3 moments from history that rhyme with this story — and how they unfolded.

November 2017 – February 2018

Milasen: first N-of-1 RNA drug (2017)

Boston Children's Hospital built a custom antisense oligonucleotide for six-year-old Mila Makovec, who had a fatal Batten disease mutation. The drug was designed and delivered in under a year.

Then

Mila's neurological decline slowed temporarily before the disease ultimately proved fatal.

Now

The case established the blueprint for patient-specific ASO development.

Why this matters now

The CHCHD10 case uses the same model with a slower disease, giving the therapy more time to show benefit.

April 2023

Tofersen approval for SOD1-ALS (2023)

The FDA granted accelerated approval to tofersen, an antisense oligonucleotide for ALS caused by SOD1 mutations, which account for about 2% of cases. It was the first gene-targeted therapy for ALS.

Then

Patients with SOD1-ALS gained the first treatment aimed at their disease's cause.

Now

It validated ASOs as a therapeutic platform for ALS and set a precedent for mutation-specific drugs.

Why this matters now

Tofersen required enough patients for a conventional trial; the CHCHD10 case is the same chemistry tailored to a mutation affecting one person.

December 2016

Nusinersen transforms spinal muscular atrophy (2016)

The FDA approved nusinersen (Spinraza), the first antisense oligonucleotide for a motor neuron disease, for spinal muscular atrophy. SMA was the leading genetic cause of infant death at the time.

Then

SMA shifted from supportive care to disease-modifying therapy with improved survival and motor milestones.

Now

The drug proved intrathecal ASOs can reach motor neurons, setting up later treatments.

Why this matters now

Nusinersen showed ASOs work for motor neuron diseases at scale. The CHCHD10 case extends that principle to a single rare mutation.