A scientist watches his mother and sisters succumb to a ruthless genetic form of ALS, yet defies the same deadly mutation through an experimental spinal infusion that has kept him symptom-free for over three years.
Story Snapshot
- Jeff Vierstra, a 41-year-old scientist, carries a familial FUS-ALS mutation that killed his mother at the age of 2 and his sisters in their 30s and 40s.
- Presymptomatic treatment with Ulefnersen at Columbia University normalized his muscle tests, marking the first known prevention attempt.
- Sisters Erin and Leigh joined the trial but died—Erin from ALS, Leigh from injury—while Vierstra thrives.
- May 2025 data from 12 patients shows FUS reduction, fueling hope for genetic ALS prevention.
Family’s Multi-Generational ALS Curse
Jeff Vierstra’s family endured ALS deaths tracing to 1800s ancestors. His mother developed symptoms in 1984 and died nine months later when Jeff was two. Her three siblings perished in their late 30s or early 40s.
This aggressive familial form stems from FUS gene mutations, which affect 1-5% of familial ALS cases—5-10% of all ALS. FUS encodes an RNA-binding protein vital for motor neuron function; mutations create toxic aggregates that destroy nerves rapidly.
Scientist whose mother and sisters died of ALS complications hopes experimental treatment will save his life https://t.co/9PQCDmuZYL
— CBS News (@CBSNews) April 5, 2026
Discovery of the FUS Mutation and Trial Path
Vierstra and sisters Erin and Leigh tested positive for the FUS mutation between 2018 and 2020. Sisters developed symptoms first. At a 2018 Barbados ALS conference, Vierstra met Dr. Neil Shneider of Columbia University’s Eleanor and Lou Gehrig ALS Center.
Shneider’s mouse studies, published in Nature Medicine, demonstrated antisense oligonucleotide ulefnersen silencing toxic FUS. The FDA approved expanded access in 2020 after an autopsy confirmed FUS reduction in the first patient.
Summer 2020 saw Erin and Leigh enroll. Vierstra joined around 2021 after electromyography detected early abnormalities, despite no symptoms. He receives spinal infusions every few months.
Sisters progressed: Erin died after about three years from ALS; Leigh after four years from an unrelated head injury. Vierstra credits the treatment with extending their lives somewhat.
Vierstra’s Breakthrough: Symptom-Free Survival
Over three years in, Vierstra remains symptom-free. His EMG normalized after one year, a stark contrast to family history. He maintains an active life skiing, traveling, and working as a scientist.
This presymptomatic start differentiates his outcome from his sisters, who began treatment post-symptoms. Dr. Shneider calls it a “very big deal” for prevention, validating FUS reduction via preclinical and autopsy data.
May 2025 results from 12 expanded access patients, now in an Ionis-sponsored trial, confirm FUS lowering and delayed damage. Shneider states the approach offers “real hope” to make ALS livable, not fatal, with plans to expand beyond FUS. Vierstra describes it as a “lease on life,” allowing future planning.
Implications for ALS Treatment and Prevention
This case proves presymptomatic gene silencing can normalize early markers in FUS-ALS, a rare aggressive subtype. Short-term, it provides proof-of-concept; long-term, it shifts paradigms toward preventing genetic ALS onset, with insights for 90% sporadic cases.
Affected include FUS-ALS patients worldwide and the broader ALS community through Columbia’s Silence ALS initiative.
Economically, it accelerates Ionis’ antisense model and gene therapies like SOD1 approvals. Socially, it reduces stigma by offering hope. Politically, FDA precedents speed rare disease access, aligning with common-sense priorities of innovation over bureaucracy.
Cautions persist: small sample size, sisters’ progression, preliminary data. Yet consensus marks it a milestone.
Sources:
Jeff’s Story: Defying Family History of ALS Through New Drug Trial (Columbia Doctors)
The FUS Involved in ALS (UTMB Health Podcast)
