The goal of this clinical study is to learn about an investigational gene therapy product called AVB-101, which is designed to treat a disease called Frontotemporal Dementia with Progranulin Mutations (FTD-GRN). FTD-GRN is an early-onset form of dementia, a progressive brain disorder that affects behavior, language and movement. These symptoms result from below normal levels of a protein called progranulin (PGRN) in the brain, which leads to the death of nerve cells (neurons), affecting the brain's ability to function.
The main questions that the study aims to answer are:
1. Is a one-time treatment with AVB-101 safe for patients with FTD-GRN? 2. Does a one-time treatment with AVB-101 restore PGRN levels to at least normal levels? 3. Could AVB-101 work as a treatment to slow down or stop progression of FTD-GRN?
In this study there is no placebo (a dummy pill or treatment used for comparison purposes), so all participants will receive a one-time treatment of AVB-101 delivered directly to the brain, with follow-up assessments for 5 years.
Male or female, 30 to 75 years of age
Carriers of a pathogenic GRN mutation
FTD as evidenced by CDR + NACC FTLD global score of 0.5, 1.0, or 2.0
Presence of 1 or more of the criteria for diagnosis of possible bvFTD or PPA
Severe dementia, defined as CDR + NACC FTLD global score of 3.0, or other symptoms that preclude the ability to comply with study procedures and/or pose unacceptable safety risk to the subject
Any concurrent disease that may cause cognitive impairment unrelated to mutations in the GRN gene, such as other causes of dementia, neurosyphilis, hydrocephalus, stroke, small vessel ischemic disease, uncontrolled hypothyroidism, or vitamin B12 deficiency
Clinically significant abnormality on MRI at Screening considered to be a contraindication to Intrathalamic infusion
Surgically significant pattern of brain atrophy on MRI at Screening that interferes with planned neurosurgical trajectory