frontotemporal

Frontotemporal dementia (FTD)—PBFT02

About PBFT02:

We are developing PBFT02 to treat FTD-GRN with a single dose of PBFT02 by intra-cisterna magna injection. PBFT02 is a gene therapy that utilizes an AAV1 viral vector to deliver a modified DNA encoding the granulin (GRN) gene to a patient's cells. The goal of this vector and delivery approach is to provide higher than normal levels of progranulin (PGRN) to the central nervous system (CNS) to overcome the progranulin deficiency in GRN mutation carriers, who have been observed to have reduced cerebrospinal fluid PGRN levels ranging from 30% to 50% of the PGRN levels observed in normal, mutation non-carriers.

About FTD:

FTD is one of the more common causes of early-onset (midlife) dementia, causing impairment in behavior, language and executive function, and occurs at similar frequency to Alzheimer disease in patients younger than 65 years. FTD presents as a rapidly progressive clinical syndrome. Changes in personal and social conduct occur in early stages of the disease, including loss of inhibition, apathy, social withdrawal, hyperorality (mouthing of objects) and ritualistic compulsive behaviors. These symptoms are severely disabling and may lead to misdiagnosis as a psychological or emotionally based problem, or, in the elderly, be mistaken for withdrawal or eccentricity. FTD progresses to immobility and loss of speech and expression. Survival averages eight years after onset of symptoms.

In approximately 5% to 10% of individuals with FTD, the disease is caused by mutations in the granulin gene, causing a deficiency of progranulin. PGRN is a complex and highly conserved protein thought to have multiple roles in cell biology, development and inflammation. Emerging evidence suggests that PGRN’s pathogenic contribution to FTD and other neurodegenerative disorders relates to a critical role in lysosomal function.

There are no disease modifying therapies approved for the treatment of FTD. Anti-depressants have been shown to manage some behavioral symptoms. We estimate the prevalence of FTD-GRN deficiency in the United States to be approximately 3,000 to 6,000.