A tailor-made drug has slowed the progression of amyotrophic lateral sclerosis (ALS) in a Florida physician, offering new evidence that precision therapies may reshape treatment for the fatal neurological disease.
Dr. Rakesh Parekh, 52, of Orlando, was diagnosed with ALS in 2021, a decade after watching his father die of the same condition. His illness was traced to a rare mutation in the gene CHCHD10, which scientists have linked to only a handful of cases worldwide. In April 2024, Parekh began receiving a personalized antisense oligonucleotide (ASO), a drug designed specifically to silence the faulty gene driving his disease.
The treatment was created by the n-Lorem Foundation, a nonprofit that develops custom therapies for patients with “nano-rare” diseases — those affecting fewer than 30 people globally. The foundation, led by biotech pioneer Dr. Stanley Crooke, covers the multimillion-dollar cost of drug development for patients who would otherwise have no options.
“Patients with nano-rare diseases have no hope, no place to go, no help,” Crooke said. “That’s why we exist.”
Slowing ALS progression
ALS gradually destroys motor neurons in the brain and spinal cord, robbing patients of the ability to move, speak, and eventually breathe. Most patients survive only two to five years after diagnosis.
Parekh’s neurologist, Dr. Bjorn Oskarsson of Mayo Clinic’s ALS Center of Excellence in Florida, said his patient’s condition has stabilized far beyond expectations. “His disease has maybe even improved a little bit,” Oskarsson noted. “He is not losing strength like he used to.”
For a disease that typically advances rapidly, such results are striking. “By the time people see a neurologist and get diagnosed, they usually only have about three years,” said Brian Pierchala, an ALS researcher at Indiana University.
A new path for treatment
ASOs work by shutting down mutated genes that produce toxic proteins. Unlike gene editing, the therapy does not change DNA but prevents the defective gene from causing further damage. Experts say early intervention is critical: neurons must still be alive for patients to regain strength.
“This is a proof of principle that, if caught early enough, you can alter the course of ALS,” said Dr. Jeffrey Rothstein, director of the Robert Packard Center for ALS Research at Johns Hopkins Medicine.
ALS has long defied treatment because it has multiple causes. About 10% of cases are inherited, and 70% of those can be linked to known mutations. For sporadic ALS, which makes up 90% of cases, only a fraction have identifiable genetic roots. Still, experts believe that as more genes are discovered, targeted therapies could eventually apply to a majority of patients.
“Our success rates are much higher if we tailor therapies to individuals with specific genetic mutations,” said Dr. Suma Babu of Massachusetts General Hospital’s Neurological Clinical Research Institute.
Progress and limitations
The Food and Drug Administration has approved just four ALS drugs since 1995. The most recent, Ionis Pharmaceuticals’ Qalsody, became the first to target a genetic mutation, SOD1, which accounts for roughly 2% of U.S. cases. Parekh’s treatment is the first designed for CHCHD10, potentially paving the way for others with the same mutation.
Still, challenges remain. “We know gene mutations for 15–20% of patients, which leaves 80% without a genetic target,” Pierchala said. Moreover, developing an ASO can take years and cost more than $1 million, limiting how quickly they can be scaled.
Living longer with ALS
Parekh has now been on the therapy for more than a year — longer than his father survived after diagnosis. He receives spinal injections every three months and continues to work, travel, and spend time with his family.
This summer, he climbed the steep stairs of the Acropolis in Greece, a feat that would have seemed impossible without treatment. “I really didn’t think there was something out there that could prolong my life or improve it,” Parekh said.
The long-term durability of the therapy remains uncertain. “We don’t have decades of experience with it,” Oskarsson acknowledged. “We are hopeful it will hold, but we do not know.”
Even so, ALS experts say this case represents a turning point. “If we can make this a livable disease for even a small group of patients, that is success,” Babu said. “If we chip away gene by gene, subtype by subtype, I think we will see real progress in ALS.”
