VIB research led by Professor Christine Van Broeckhoven helped enable the development of PR006, a novel gene therapy that is now being evaluated as a potentially disease-modifying, single-dose gene therapy for individuals living with frontotemporal dementia with GRN mutations (FTD-GRN). The PR006 phase 1/2 PROCLAIM clinical trial, sponsored by the U.S. company Prevail Therapeutics, a wholly-owned subsidiary of Eli Lilly and Company, is enrolling patients in clinical centers across multiple countries.
Early-onset dementia, a high unmet medical need
Frontotemporal dementia is the second most common form of early-onset dementia after Alzheimer’s disease. This type of dementia is characterized by progressive loss of nerve cells in the frontal and temporal lobes of the brain. Patients generally present with changes in behavior and personality or with language problems. Eventually, these symptoms make normal social interaction impossible. Unfortunately, there is currently no treatment, and patients usually pass away 6 to 8 years after the first symptoms appear.
VIB has a rich history in the research of neurodegenerative diseases
Professor Christine Van Broeckhoven and her team at VIB and the University of Antwerp have a strong tradition in molecular genetics of neurodegenerative diseases. Working in collaboration with Michael Hutton at Mayo Clinic (now at Eli Lilly) and Howard Feldman and Ian Mackenzie at the University of British Columbia, Christine Van Broeckhoven’s team uncovered in 2006 that mutations in the GRN gene are the basis of a common familial form of frontotemporal dementia. These genetic mutations lead to a shortage of the growth factor progranulin in the brain, leading to the disease. This work of professor Van Broeckhoven, together with collaborators from the Mayo Clinic, the University of British Columbia, and the University of Manchester, was published in two papers of the prominent scientific journal Nature.
Turning scientific discoveries into therapies
Because these findings brought to light that strategies to increase progranulin levels could be valuable to prevent or treat dementia, VIB reached out to an industrial partner to develop these insights into a treatment for patients. In 2019, VIB closed a non-exclusive license agreement with the U.S. company Prevail Therapeutics for the development of gene therapy for patients with FTD-GRN.
Prevail Therapeutics, a wholly-owned subsidiary of Eli Lilly and Company, is currently testing the developed gene therapy in a phase 1/2 clinical trial in the U.S. and Australia. PR006 is designed to slow or stop disease progression in FTD-GRN patients by increasing progranulin levels via delivery of a healthy GRN gene into the central nervous system (CNS).