The FDA has allowed a clinical trial to proceed for an experimental gene therapy for mucolipidosis Type IV, or MLIV, an inherited neurodegenerative disease affecting fewer than 100 known children worldwide.
The first-in-human study will evaluate a therapy supported by the Mucolipidosis Type IV Foundation, a family-founded nonprofit that has coordinated and funded research, manufacturing, toxicology and regulatory work for the program.
MLIV is caused by mutations in the MCOLN1 gene, which lead to a deficiency of mucolipin-1, a protein needed for normal cellular function. The condition causes severe neurological and developmental impairment. Most children with MLIV do not learn to walk or talk, generally function at about a 15-month developmental level, develop progressive vision loss and have shortened life expectancies, according to the foundation. No approved disease-modifying treatment exists.
The investigational therapy uses an adeno-associated virus serotype 9, or AAV9, vector to deliver a functional copy of the gene responsible for producing mucolipin-1. It is intended to allow cells to produce the protein missing in people with MLIV.
A neurosurgeon will administer the therapy directly into the brain using an approach designed to reach selected areas of the central nervous system. Patients will also receive temporary immune suppression associated with administration of the AAV-based therapy.
The ML4 Foundation began prioritizing gene-therapy research in 2017. Research at Massachusetts General Hospital, led by Susan Slaugenhaupt and Yulia Grishchuk, produced mouse-model findings published in 2021 that indicated the therapy corrected neurological dysfunction.
In 2023, the foundation engaged Miguel Sena-Esteves, Heather Gray-Edwards and the University of Massachusetts Gene Therapy Center to complete preclinical work and develop the clinical program. Charles River Laboratories conducted toxicology studies, while Andelyn Biosciences produced clinical-grade drug material.
The foundation said stability, sterility, potency, compatibility and dose-related testing supported the investigational new drug application.
Researchers do not yet know whether the therapy will provide clinical benefit, how quickly any benefit may appear, whether patients will respond similarly or what adverse effects could occur. Trial eligibility and enrollment information will be released after participating institutions complete remaining steps. The foundation hopes to begin treating children in 2026.
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