Global tally of frontotemporal dementia drug trials: just twelve

A scoping review of three international trial registries found only twelve interventional studies worldwide testing disease-modifying drugs for frontotemporal dementia, split evenly between gene therapies for a rare inherited form and anti-inflammatory drugs aimed at the more common sporadic disease.

A scoping review published in the journal Neurosci counted twelve interventional clinical trials worldwide testing disease-modifying pharmacological treatments for frontotemporal dementia (FTD), the first systematic census of this specific pipeline. Researchers Patrick Bartoshyk and Ronan O'Caoimh, of the University of Limerick and University College Cork, searched the US National Library of Medicine's ClinicalTrials.gov, the European Union Clinical Trials registry, and the Australian New Zealand Clinical Trials Registry through September 2025. No licensed disease-modifying therapy currently exists for FTD; treatment remains symptomatic only.

Of the twelve trials identified, six targeted an inherited form of FTD caused by mutations in the progranulin (GRN) gene, using gene replacement or gene therapy approaches; the other six targeted neuroinflammation in sporadic FTD, the more common form not linked to a single known genetic cause. Among the GRN-targeted studies, the review's authors described three early-phase (phase 1/2) gene replacement trials, named PROCLAIM, ASPIRE-FTD and upliFT-D, plus one immune-modulating monoclonal antibody trial called INFRONT, which has since moved into phase 3. The review reported that interim results from these early-phase, randomized controlled trials showed safety, tolerability and effectiveness at raising progranulin levels in participants with the GRN mutation, though the authors did not report data showing these changes altered the course of dementia symptoms.

The review is a count of what has been registered on trial databases, not a clinical trial itself, and it draws on interim and early-phase data for the gene therapy studies. Family members and clinicians should note that raising a protein level in blood or spinal fluid is a biomarker outcome, distinct from evidence that a drug slows cognitive or functional decline; the authors describe those cognitive-outcome results as still pending for most of the twelve trials. The review's authors also noted that two phase 2 randomized controlled trials targeting sporadic FTD have recently completed, without yet reporting whether they showed benefit.

The authors call for continued expansion of the trial pipeline, particularly for sporadic FTD, which lacks the clear genetic drug target that has focused progranulin research to date.