a study to evaluate the safety and effect of avb-101, a gene therapy product, in subjects with a genetic sub-type of frontotemporal dementia (ftd-grn)

Conditions: Frontotemporal Dementia; FTD; FTD-GRN; Dementia, Frontotemporal

Summary: 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.


Eligibility criteria:
inclusion criteria: * 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 * a protocol defined minimum thalamic volume on each side on screening mri * able and willing to comply with all procedures and the study visit schedule * able and willing to give written informed consent prior to study participation, and agree to designate a legal representative to act on their wishes to continue participation should they lose capacity to consent at some point during the study * an identified, informed study partner who is able and willing to support the participant in the study and to provide assessments of the participant during the study exclusion criteria: * 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 * previous treatment with any gene or cell therapy * previous treatment with any investigational medicinal product (imp) within 60 days or 5 half-lives (whichever is longer) prior to study drug treatment * concomitant disease, any clinically significant laboratory abnormality, or treatment which, in the opinion of the investigator, may pose an unacceptable safety risk to the participant or interfere with study conduct or the participant's ability to comply with study procedures including neurosurgical administration under anesthesia

Keywords: gene therapy aav intrathalamic intraparenchymal progranulin behavioral variant ftd primary progressive aphasia pgrn granulin dementia dementia gene therapy aav9