Abstract Details

Title A Phase 2 Study of AL001 in Frontotemporal Dementia Patients Carrying a Granulin Mutation

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P5 - Poster Session 5 (11:45 AM-12:45 PM)

Poster/Presentation
Number 3-005

Objective INFRONT-2 is an open-label, Phase 2 study in GRN mutation carriers to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of AL001 administered intravenously every four weeks.

Background

Frontotemporal dementia (FTD) is a rare, early-onset form of dementia and loss-of-function mutations in the progranulin gene (GRN) are a common cause of familial FTD. In the brain, progranulin (PGRN) is a key regulator of microglia activity and lysosomal function. AL001 is a human monoclonal IgG1 antibody that blocks and downregulates Sortilin, a receptor in the key degradation pathway of PGRN, and is being developed by Alector for the treatment of carriers of GRN mutations causative of FTD (FTD-GRN). Restoring PGRN levels may be an effective therapeutic approach in FTD-GRN.

Design/Methods Participants aged 18 – 85 years, must be carriers of a GRN mutation causative of FTD, have a CDR® plus NACC FTLD global score of 0.5 – 2, and have 1 or more of the 6 behavioral/cognitive symptoms required for a diagnosis of possible bvFTD (Rascovsky 2011) or a diagnosis of PPA (Gorno-Tempini 2011). Lumbar punctures and MRI scans were performed at baseline and every 6 months. Clinical assessments were done every 3 months. Fluid biomarkers were analyzed using multiple platforms.

Results AL001 continues to be well tolerated in FTD-GRN participants in INFRONT-2. Chronic dosing led to a sustained increase in PGRN levels to the normal range in FTD-GRN participants. Biomarker data related to key aspects of FTD-GRN pathophysiology and neurodegeneration will be presented for INFRONT-2 participants who have received AL001 for 12 months.

Conclusions AL001 is being developed for the treatment of FTD-GRN to reduce the rate of neurodegeneration by increasing levels of PGRN and disrupting the pathophysiological disease cascade associated with FTD-GRN.

Authors/Disclosures
Julie Huang, PhD (Alector) PRESENTER	Dr. Huang has received personal compensation for serving as an employee of Alector, Inc. Dr. Huang has stock in Alector.
Robert Paul, MD, PhD	Dr. Paul has received personal compensation for serving as an employee of Alector. Dr. Paul has received stock or an ownership interest from Alector.
	No disclosure on file
Michael Ward	Michael Ward has received personal compensation for serving as an employee of Alector. Michael Ward has stock in Alector. Michael Ward has received intellectual property interests from a discovery or technology relating to health care. Michael Ward has a non-compensated relationship as a Reviewer with ADDF that is relevant to AAN interests or activities.
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file

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