New Medicines

Frontotemporal dementia, caused by mutations in the granulin (GRN) gene 


New molecular entity
Passage Bio
Passage Bio

Development and Regulatory status

Phase II Clinical Trials
Phase II Clinical Trials
Mar 21FDA grants fast track designation for PBFT 02 for treatment of patients with frontotemporal dementia with granulin mutations (FTD-GRN) [4].
Jan 21Granted orphan drug status in the US [4].


An optimised adeno-associated virus (AAV)-granulin gene therapy, using an AAV serotypes 1 (AAV1) viral vector to deliver a modified DNA encoding the GRN gene to a patients cells. The therapy is being developed as a single dose administered via intra-cisterna magna injection formulation.
FTD is much less common than Alzheimers disease and vascular dementia. Figures vary, but it probably accounts for less than 5% of all dementia. The incidence of FTD is estimated to be 1.61 to 4.1 cases per 100,000 people annually [1]. GRN-FTD represents about 5% of all FTD, and 20% of FTD in which the family history is positive. It is inherited in an autosomal dominant manner [2].
Frontotemporal dementia, caused by mutations in the granulin (GRN) gene 

Trial or other data

PI/II upliFT-D trial to evaluate the safety, tolerability and efficacy of single dose of PBFT 02 for the treatment of patients with frontotemporal dementia with mutations in the progranulin gene (FTD-GRN) starts (NCT04747431; PBFT02-001). The multicenter, open-label, single-arm, dose-escalation trial intends to enroll six patients aged 35 to 75 years in the US, Brazil, Canada and the UK (in Cambridge). Two dose levels of PBFT02 will be studied in patients with FTD-GRN. The study will sequentially enroll 2 cohorts. An optional third dose level cohort may be enrolled based on the results of the first two cohorts. This is a 5-year study, with a 2-year main study, followed by a 3-year safety extension. Primary outcomes include change in nerve conduction velocity and amplitude from baseline on nerve conduction studies; collection of these data is due to complete Aug 24 [3].