Preclinical and clinical investigation of VES001, an oral small molecule sortilin receptor inhibitor for the treatment of frontotemporal dementia: a first-in-human randomized placebo-controlled phase 1 trial.

What was studied

This early trial tested VES001 in healthy adults. VES001 is an oral drug that blocks sortilin. GRN gene changes lower progranulin and cause frontotemporal dementia. VES001 raises progranulin. Lab work in male rats came first. Then 79 healthy adults got VES001 or placebo. The trial was randomized and double-blind. Single doses ran from 10 to 990 mg. Repeat doses were given for 7 days.

What they found

No deaths or serious adverse events occurred. No one stopped because of treatment. Headache and fatigue were mild. They were not dose-related. Drug levels rose in step with the dose. The drug entered the brain from the blood. Single doses raised plasma progranulin. Repeat doses gave greater, lasting rises than placebo. Rises were seen in plasma and spinal fluid.

What it means for patients

The authors say the findings show proof of mechanism for oral sortilin inhibition. They say this supports more development of VES001 as a possible disease-modifying therapy for FTD-GRN.

Why it is not certain yet

The cohorts were small. Dosing lasted 7 days. Participants were healthy, not people with dementia. The abstract reports no effect on dementia symptoms. The abstract names rats only for the lab work.

Source

Preclinical and clinical investigation of VES001, an oral small molecule sortilin receptor inhibitor for the treatment of frontotemporal dementia: a first-in-human randomized placebo-controlled phase 1 trial.

We restate facts from the source record in our own words. The original wording belongs to its publisher.