Mark Forman, MD, PhD, on ICM Administration of Gene Therapy in Frontotemporal Dementia


The chief medical officer of Passage Bio discussed the phase 1/2 upliFT-D study of PBFT02.

"PBFT02 uses a viral vector, the AAV1 vector, to administer the drug with the intracisterna magna approach to directly deliver the viral vector to the CSF fluid which surrounds the brain. Our thought is that this will correct the deficiency associated with granular gene mutationsresulting in a reduction in the amount of progranulin protein in the body.”

Passage Bio’s phase 1/2 upliFT-D study (NCT04747431) has dosed its first patient with frontotemporal dementia with granulin mutations (FTD-GRN) with the gene therapy PBFT02. upliFT-D study is a 2-year study with a 3-year safety extension evaluating PBFT02 delivered via intracisterna magna (ICM) injection. The trial is currently enrolling patients between the ages of 35 to 75 years with early symptomatic FTD-GRN to be evaluated in 2 cohorts of 2 dose levels of PBFT02, with an optional third dose cohort.

PBFT02 uses the AAV1 vector to deliver the GRN gene to the ICM in patients with FTD-GRN. GRN encodes progranulin, a deficiency of which is thought to contribute to lysosomal dysfunction. The therapy has shown preclinical efficacy in studies conducted by University of Pennsylvania’s Gene Therapy Program, Passage Bio’s collaborator on the program.

CGTLive spoke with Mark Forman, MD, PhD, chief medical oficer, Passage Bio, to learn more about the trial and its goals. He discussed the lack of treatments in the FTD-GRN space and PBFT02’s potential to improve outcomes for these patients.

More information about the upliFT-D global trial and eligibility is available at

Passage Bio doses first patient in global clinical trial of PBFT02 gene therapy for frontotemporal dementia with granulin mutations. News release. Passage Bio. August 11, 2022.
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