Jeff’s Story: Defying a Family History of ALS through a New Drug Trial

You could say Jeff Vierstra is a glass-half-full kind of person. At age 16, he was diagnosed with leukemia that went into remission after treatment in a clinical trial. When the cancer returned after three years, Jeff had a bone marrow transplant that cured the disease.

Nearly 20 years later, Jeff, now a researcher who studies mechanisms that turn genes on and off, found himself discussing a different condition at a scientific conference in Barbados.

“Some of the scientists gave this amazing talk about the work they were doing in ALS,” says Jeff. Intrigued, he told the researchers that his mother and her three siblings had died of ALS while they were still in their 30s and 40s. In addition, Jeff’s genealogical history going back to the 1800s revealed that many family members had died in their 30s and 40s, suggesting that ALS had a strong genetic component.

A fatal disease without a cure, ALS, or amyotrophic lateral sclerosis, is a neuromuscular condition that damages motor neurons in the spinal cord and brain. It is typically diagnosed in people aged 50 and older, but younger people, including those with certain gene mutations, can also develop the disease.

“Nobody really knew if my mother, her siblings, and their grandmother had ALS,” Jeff says. "Now you can get your genome sequenced and have other tests. But back then, the tools for understanding and diagnosing ALS didn’t exist.”

The Road to Columbia

Two years after Jeff attended the conference, his oldest sister, Erin, started having neuromuscular symptoms, including upper body weakness, but was unable to get an appointment with a neurologist. Alarmed, Jeff called Hemali Phatnani, PhD, one of the scientists he had met at the conference. Dr. Phatnani immediately connected him to Neil Shneider, MD, PhD, a Columbia neurologist who studies genetic forms of ALS. One area of Dr. Shneider’s work focuses on an ultra-rare type of the disease caused by mutations in a gene that makes a protein, called FUS, that is toxic to motor neurons.

“FUS ALS is one of the most aggressive forms of the disease, striking teens and young adults and often killing within months of symptom onset,” says Dr. Shneider.

Dr. Shneider invited Erin, Jeff, and a third sibling, Leigh, to come to Columbia for genetic testing. The tests confirmed that all three had the mutated gene.

There are no approved treatments for FUS ALS, and time was of the essence—the siblings' mother died nine months after her symptoms began. Was there a way to help them avoid their mothers’ fate?

Dr. Shneider believed there might be. He had tested an experimental therapy in mice with FUS mutations. His study in Nature Medicine showed that the drug, created by Ionis Pharmaceuticals, silenced the gene, reducing FUS levels in the brain and spinal cord and delaying motor neuron damage.

With these results, Dr. Shneider obtained FDA approval to give the experimental drug to patients with FUS ALS through an investigator-initiated, expanded access program. The first patient, a young woman whose disease advanced rapidly, died about a year after starting treatment. However, an autopsy revealed that the drug had markedly reduced toxic protein levels in her brain, with no apparent side effects.

In the summer of 2020, both Erin and Leigh, who had high levels of a biomarker associated with motor neuron damage, enrolled in the program.

Though Jeff did not have symptoms, tests of electrical activity in his muscles indicated that he would likely develop symptoms soon. So when he was also invited to enroll as a presymptomatic patient, he did not hesitate.

“A hard challenge with ALS is dealing with the uncertainty, especially if you are presymptomatic,” Jeff says. “Starting the treatment seemed like the best thing I could possibly do to improve my odds of survival.”

Looking to the Future

Though Erin received the treatment for about three years, she continued to slowly decline and eventually passed away. Leigh, who had regained some of her mobility and no longer needed continuous breathing assistance, died of a head injury unrelated to the drug after four years of treatment.

Dealing with the loss of his siblings has been hard for Jeff. “Seeing my sisters go through all of this, and knowing we had the same mutation, is tragic, and at the same time I can’t help but wonder about my own future,” Jeff says.

But the trial also gives Jeff a reason to be hopeful. The abnormal electrical activity in his muscles has improved, and he remains symptom-free after more than three years of treatment.

Results from the first 12 patients treated through the expanded access program, who subsequently enrolled in an ongoing clinical trial sponsored by Ionis, were published in May 2025.

“These responses suggest that if we intervene early enough and go after the right target at the right time in the course of this disease, it’s possible not only to slow disease progression but actually reverse some of the functional losses,” Dr. Shneider says.

As the clinical trial continues, Jeff is optimistic about the future and the opportunity to continue his treatment through a clinical trial sponsored by the drug’s developer.

“Seeing ALS rob my sisters and mom’s lives was devastating,” Jeff says. “But in other ways, I am very fortunate: The fact that I happened to be at a conference in Barbados, where I met a scientist who worked with a researcher who was testing a drug that was essentially ready-made for the genetic mutation our family had was kind of crazy,” Jeff says.