Alector aims to seek FDA approval of Parkinson’s therapy in 2027
Company says it's advancing AL050 toward studies to support application
Alector said it is advancing the development of AL050, an enzyme replacement therapy for Parkinson’s disease, with an eye toward submitting an investigational new drug application to the U.S. Food and Drug Administration (FDA) in 2027.
“We are well-resourced to advance our portfolio of innovative drug candidates for the treatment of neurodegenerative diseases, with a sharpened focus on our differentiated Alector Brain Carrier (ABC) platform,” Arnon Rosenthal, PhD, Alector’s CEO, said in a company press release.
Mutations in the GBA1 gene, which provides instructions for producing the glucocerebrosidase (GCase) enzyme, are one of the most common genetic causes of Parkinson’s. When GCase is faulty or missing, toxic clumps of misfolded proteins accumulate inside nerve cells, contributing to their gradual loss and subsequent Parkinson’s symptoms. AL050 is designed to deliver a functional version of the GCase enzyme to the brain.
Accessing the brain
One of the most significant challenges in treating neurodegenerative diseases is the effective delivery of treatments across the blood-brain barrier (BBB), a tight layer of cells that helps protect the brain against potentially harmful substances but also restricts the delivery of many therapeutics.
AL050 features an engineered GCase with improved activity and stability, which can be effectively delivered to the brain using ABC technology. The technology leverages the transferrin receptor, which is expressed by cells that line blood vessels, allowing substances to cross the BBB through the cells, rather than between them. This allows therapeutic agents to reach the brain at effective levels, contributing to reducing treatment dosage and minimizing side effects.
“Our ABC-enabled programs have demonstrated robust brain penetration …, favorable safety, and good pharmacokinetics,” Rosenthal said. “ABC represents an important driver of innovation, with the versatility to deliver antibodies, enzymes and nucleic acid to the brain.” Pharmacokinetics refers to the movement of the therapy into, through, and out of the body.
Preclinical studies showed AL050 increased GCase activity and reduced toxic substrate accumulation in animal models of GBA disease, supporting its potential as a therapy for Parkinson’s disease and Lewy body dementia associated with loss-of-function mutations in the GBA gene.
The company is also developing ADP062-ABC, a therapy for Parkinson’s that’s intended to reduce the accumulation of toxic clumps of alpha-synuclein, which is thought to be a primary driver of nerve cell loss in the disease.
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