Summary:
AVB-101 is a gene therapy for frontotemporal dementia intended to deliver a functional copy of the GRN gene to the brain. The study will collect data to evaluate how safe AVB-101 is, as well as whether AVB-101 restores normal progranulin protein levels in the brain. Investigators will also evaluate whether it works to slow or stop the progression of FTD in participants with GRN genetic variants.
Who is eligible?
- Men and women aged 30 to 75 years.
- Carries a pathogenic progranulin gene (GRN) variant
- Has a Clinical Dementia Rating® plus National Alzheimer's Coordinating Center frontotemporal lobar degeneration global score of 0.5, 1.0 or 2.0
- Meets one or more criteria for behavioral variant FTD or Primary Progressive Aphasia (PPA)
- Has a reliable study partner who can provide information about the participant’s health and functional abilities and speaks to the participant at least weekly
- Is able to provide informed consent and is willing to designate a legally authorized representative
- Does not have severe dementia (Clinical Dementia Rating® plus National Alzheimer's Coordinating Center frontotemporal lobar degeneration global score 3.0)
- Has not had any type of gene therapy
- Participants who have received other experimental treatments may be permitted—eligibility will depend on the time since the last last administration of the therapy
- Has not received any other diagnosis or been informed of any other genetic risk factors which would reasonably explain the symptoms
Interested individuals meeting the above requirements should contact the study coordinator for additional requirements and exclusions if interested in participating.
What will happen during the study?
This study is divided into 2 groups. Everyone in the study will receive a single dose of the experimental treatment. Group 2 will receive a higher dose than group 1. The experimental treatment will be injected into an area of the brain called the thalamus using an MRI guided stereotaxic infusion. This means that MRI will be used to locate the right spot, a small hole will be made in the skull and the experimental medicine will be injected into the brain. The specific group into which a participant is placed will be based on when he/she joins the study. All study participants will receive the experimental treatment.
What are they measuring to evaluate the experimental treatment?
- Side effects and reactions to the experimental treatment
- Changes in cognitive status
- Changes in brain structure based on MRI
- Changes in progranulin protein levels and neurofilament light levels in blood and spinal fluid
- Changes in a clinical rating scale called the CDR plus NACC FTLD, which stands for “Clinical Dementia Rating (CDR)+ National Alzheimer's Coordinating Center (NACC) frontotemporal lobar degeneration (FTLD)”
- Changes in additional cognitive, behavioral and activities of daily living assessments
- Changes in additional biomarkers measured through blood samples and spinal fluid
How long will participants be involved in the study?
Study participants will be monitored for 5 years.
