The US FDA has allowed an investigational new drug (IND) application to proceed for AAV-MCOLN1, an adeno-associated virus gene therapy for mucolipidosis type IV (MLIV), clearing the way for what researchers describe as the first interventional clinical trial in the ultra-rare pediatric neurodegenerative disease. The program was developed by researchers at UMass Chan Medical School and Mass General Brigham with support from the Mucolipidosis Type IV (ML4) Foundation.
Why it matters: MLIV has no approved disease-modifying treatment and affects only around 100 known patients worldwide. AAV-MCOLN1 is designed to address the underlying genetic defect by delivering a functional copy of MCOLN1, potentially offering the first therapeutic approach aimed at altering disease progression rather than providing supportive care.
The therapy uses an AAV vector to restore expression of mucolipin-1, or TRPML1, a lysosomal ion channel disrupted in MLIV. Preclinical development included central nervous system-directed delivery and additional studies requested by the FDA before the IND was allowed to proceed.
The Phase I/II trial will evaluate safety and preliminary efficacy in children with MLIV at UMass Chan. Elenora D'Ambrosio, MD, and Amanda Nagy, MD, will lead the clinical study, with Oguz Cataltepe, MD, serving as lead neurosurgeon.