Frontotemporal dementia (FTD) is a devastating form of early-onset dementia characterized by rapid decline in executive function, behavior, and/or language. It typically leads to death within 7-13 years of symptom onset and is a leading cause of dementia in those under 65 years old, with an estimated prevalence of up to 4.6 cases per 1,000 population at any given time. FTD has a substantially greater impact on work, family, and finances than Alzheimer's disease due to its earlier age of onset, often striking between ages 45-68.

FTD can be familial or sporadic, with around one-third of cases being familial and having a strong genetic component. The majority of hereditary FTD cases are caused by autosomal dominant mutations in three genes, including the GRN (progranulin) gene. Approximately 11,000 people in the U.S. and EU5 are living with FTD due to GRN mutations (FTD-GRN), with around 2,000 new cases confirmed annually. As disease education and access to genetic testing improve, the numbers of diagnosed and at-risk individuals are expected to increase.

Currently, there are no disease-modifying treatments available for FTD. AVB-101 is an investigational gene therapy aimed at treating FTD-GRN. It is an AAV-based gene supplementation therapy designed to deliver a functional GRN gene copy to restore progranulin levels in the brain via a one-time administration.

The ASPIRE-FTD Phase I/II clinical study will evaluate AVB-101 delivered into the thalamus of FTD-GRN patients. Preclinical data suggests this could increase progranulin levels in cortical brain regions and restore physiological function. To date, 3 subjects have been dosed, and the study is actively recruiting in Poland, Spain, the Netherlands and the USA, with additional countries/sites planned. Preliminary data suggest acceptable safety and tolerability of AVB-101, including the administration procedure.