Abstract Details

Title Development of the Monoclonal Antibody AL101 to block the Sortilin/Progranulin Interaction as a Potential Therapy for Neurodegenerative Diseases

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P6 - Poster Session 6 (5:30 PM-6:30 PM)

Poster/Presentation
Number 3-003

Background Progranulin (PGRN) is a pleiotropic protein involved in lysosomal function, inflammation, neuronal survival and neurite outgrowth. Novel risk loci that modify PGRN levels have been identified by GWAS studies in Alzheimer’s (AD) and Parkinson’s diseases (PD). The GRN SNP rs5848 is associated with reduced PGRN expression and increased AD risk (Bellenguez et al, 2020). Plasma PGRN levels reportedly decrease in PD with increased disease severity on the Hoehn and Yahr scale and increased Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) scores (Yao et al, 2020). The Sortilin receptor acts as the major regulator of PGRN and blocking Sortilin raises PGRN levels in healthy volunteers. PGRN is being investigated as a therapeutic target for treating neurodegenerative diseases.

Objective AL101 blocks the Sortilin/PGRN interaction and is a potential therapy for neurodegenerative diseases.

Design/Methods

Alector has generated a therapeutic candidate human recombinant monoclonal antibody, AL101, that binds specifically to Sortilin.

Results AL101 binds Sortilin with a high affinity, decreases the levels of the receptor, and blocks the PGRN/Sortilin interaction. AL101 treatment increases PGRN levels in plasma and cerebrospinal fluid of rodents, non-human primates, and healthy volunteers.

Conclusions AL101 is being developed for the treatment of Alzheimer's Disease and Parkinson's Disease.

Authors/Disclosures
Ananya Mitra, PhD (Alector Biotechnology) PRESENTER	Dr. Mitra has received personal compensation for serving as an employee of Alector Biotechnology. Dr. Mitra has stock in Alector Biotechnology. Dr. Mitra has received intellectual property interests from a discovery or technology relating to health care.
Robert Paul, MD, PhD (Nine Square Therapeutics)	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
	No disclosure on file
	No disclosure on file
	No disclosure on file
Erik Roberson, MD, PhD (University of Alabama at Birmingham)	Dr. Roberson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lilly. The institution of Dr. Roberson has received research support from NIH. The institution of Dr. Roberson has received research support from Alzheimer's Drug Discovery Foundation. The institution of Dr. Roberson has received research support from Bluefield Project. Dr. Roberson has received intellectual property interests from a discovery or technology relating to health care. Dr. Roberson has received publishing royalties from a publication relating to health care.
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.
Stella McCaughey, PhD	Dr. McCaughey has received personal compensation for serving as an employee of Alector, Inc. Dr. McCaughey has received stock or an ownership interest from Alector, Inc.
Nadine Tatton, PhD	Dr. Tatton has received personal compensation for serving as an employee of Alector, Inc. Dr. Tatton has received stock or an ownership interest from Alector.
Michael Kurnellas (Stanford University)	Michael Kurnellas has received personal compensation for serving as an employee of Alector. Michael Kurnellas has received stock or an ownership interest from Alector. Michael Kurnellas has received intellectual property interests from a discovery or technology relating to health care.