HQ Team
27 November, 2025: A new once-a-day pill designed to stop frontotemporal dementia (FTD) has cleared its first major safety test, researchers announced Monday. In a small two-centre trial, six healthy people who carry the genetic mutation most strongly linked to FTD took the experimental capsule, VES001, for three months. None dropped out or suffered serious adverse events, and blood and spinal-fluid levels of the protective protein progranulin jumped an average of 95 % above baseline, the Dutch–UK team reported in a company release.
said Chief Scientific Officer Anders Nykjær of Vesper Bio, the Danish biotech behind the pill. “Conceptually, this could transform dementia therapy from late-stage care to true prevention.”
FTD is the commonest form of dementia in people under 60, accounting for roughly one in five early-onset cases. Mutations in the GRN gene halve production of progranulin, a growth factor that keeps neurons alive. Gradual progranulin starvation leads to shrinkage of the frontal and temporal lobes, robbing patients of personality, language and executive function, usually in their 50s. Because affected families often know their mutation status decades before symptoms, a safe preventive has been a Holy Grail.
How the pill works
VES001 targets sortilin, a receptor that sweeps progranulin out of brain cells and into degradation pathways. By quieting sortilin, the small molecule lets the scarce progranulin linger longer, effectively raising its functional concentration. Researchers liken it to “putting a plug in a leaky bucket” rather than trying to pour more water in.
The Phase I programme enrolled 24 volunteers across University College London and the Netherlands’ Leiden University. Eighteen were non-carriers used for basic safety; six were asymptomatic GRN-carriers. All took 250 mg VES001 daily with food. Laboratory assays showed parallel rises in plasma and cerebrospinal progranulin, hinting the drug crosses the blood–brain barrier as hoped. MRI scans revealed no swelling, bleeds or liver changes; side-effects were limited to mild headache and loose stools.
cautioned neurologist Jonathan Rohrer, principal investigator at the Queen Square Institute of Neurology.
“Still, for families who watch relatives fade year after year, any glimmer of prevention is huge.”
Tiny arsenal of dementia drugs
If future trials confirm benefit, VES001 would join a still-tiny arsenal of disease-modifying dementia drugs—all of them until now antibody infusions rather than pills.
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Aducanumab (Aduhelm™) was the first, approved by the FDA in 2021 amid controversy; its ability to slow cognitive decline remains disputed, and many insurers restrict coverage.
- Lecanemab (Leqembi™), developed by Eisai and Biogen, became the first therapy to win full U.S. approval (July 2023) after showing a 27 % slowing of decline over 18 months in early Alzheimer’s. It is given twice-monthly intravenous infusions and can cause brain swelling (ARIA) especially in people with two copies of the APOE-ε4 gene.
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Donanemab, from Eli Lilly, posted 35 % slowing in a subset of patients and is under regulatory review; like lecanemab, it is an IV anti-amyloid antibody and carries similar ARIA risk.
All three agents target amyloid-β plaques, the sticky clumps found in Alzheimer’s but not in FTD, underscoring the need for tissue-specific approaches such as progranulin restoration.
Sage Therapeutics Inc.’s experimental drug failed to meet its main goal of treating mild dementia due to Alzheimer’s disease and the US, Cambridge-headquartered company has halted its trials.
The mid-stage trial of dalzanemdor drug “did not demonstrate a statistically significant difference from baseline in participants treated with dalzanemdor versus placebo on the primary endpoint,” according to a company statement.
Road ahead
Vesper Bio will launch a multi-centre Phase II study in 2026, enrolling 120 GRN-mutation carriers for at least 18 months to see whether progranulin rises translate to stable brain volumes and intact cognitive scores. If successful, a Phase III prevention trial—potentially lasting five to seven years—could start before the decade ends. Regulators on both sides of the Atlantic have already granted orphan-drug status, smoothing the path.
Scientists agree the journey is far from over, but after decades of Alzheimer’s setbacks, an oral pill with a clean safety sheet and a clear biomarker win feels like a fresh page.
As Nykjær put it, “We don’t claim victory yet, but for the first time we can say: the pill is safe, the target is engaged, and the clock may be ticking in our favour.”
