Summary:
PBFT02 is an experimental gene therapy for frontotemporal dementia intended to deliver a working copy of the GRN gene to the brain to replace the gene that doesn’t work in people with frontotemporal dementia and genetic variants in the progranulin gene (FTD-GRN). This study will collect data to assess whether the experimental treatment is safe, whether it is effective at improving cognitive function, behavioral or language symptoms and how the different doses compare related to safety and effectiveness.
Who is eligible?
- Men and women aged 35 to 75 years
- Carries a pathogenic progranulin gene (GRN) variant
- Has a clinical diagnosis of frontotemporal dementia (FTD)
- 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 not living in a nursing home
- Has not had any type of gene therapy
- Participants who have received other therapies that may impact progranulin levels 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
- Is able to provide informed consent or has a legally authorized representative who is able to provide informed consent
Additional exclusion criteria related to other medical conditions (e.g. cancer, recent hospitalization, use of blood thinners, etc) apply. 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 with an optional third group. Everyone in the study will receive a single dose of the experimental treatment. The experimental treatment will be injected into an area at the base of the skull called the intra cisterna magna. The specific group into which a participant is placed will be based on when he/she joins the study.
Group 1:
- 33 billion gene copies per gram of estimated brain weight
Group 2:
- 110 billion gene copies per gram of estimated brain weight
Group 3 (optional):
- 220 billion gene copies per gram of estimated brain weight
What are they measuring to evaluate the experimental treatment?
- Side effects and reactions to the experimental treatment
- Changes in nerve conduction to see how fast electrical impulses travel through your body. This will be measured with a nerve conduction velocity test at multiple time points during the study
- Immune responses to the gene therapy and the virus that is used to deliver the gene therapy. This will be measured in blood and spinal fluid
- Changes in progranulin levels in blood and spinal fluid at multiple time points during the study
- 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
- Changes in brain volume using magnetic resonance imaging (MRI)
How long will participants be involved in the study?
Study participants will be monitored for 5 years.
