FDA Allows First Gene Therapy Clinical Trial for Ultra-Rare Pediatric Neurodegenerative Disease

The FDA has cleared the way for the first U.S. clinical trial of an experimental gene therapy for mucolipidosis type IV, or MLIV, an ultra-rare inherited neurological disorder affecting fewer than 100 known children worldwide.

The agency allowed the ML4 Foundation’s investigational new drug application, or IND, to proceed, enabling researchers to take the remaining steps needed to enroll and treat children in a first-in-human study. The foundation said it hopes the first participants could receive the therapy later in 2026.

The effort underscores the growing role of patient-founded nonprofits in rare-disease drug development. With so few patients, ultra-rare disorders often attract limited commercial investment, leaving families and advocacy groups to fund research, organize scientific collaborations and build the evidence needed to advance potential treatments into human trials.

MLIV is caused by mutations in the MCOLN1 gene, which provides instructions for making a protein called mucolipin-1. Without enough of that protein, children develop severe neurological and developmental impairments. Many never learn to walk or talk, experience progressive vision loss and have shortened life expectancies. No approved treatment currently slows or alters the disease’s course.

The experimental treatment uses a modified adeno-associated virus, known as AAV9, to carry a working copy of the MCOLN1 gene into targeted regions of the brain. A neurosurgeon would administer the therapy directly into the brain, and patients would receive temporary immunosuppression as part of the procedure.

The goal is to help cells produce mucolipin-1, addressing the disease’s underlying genetic cause rather than treating symptoms alone. But the therapy has never been tested in a person with MLIV, and researchers do not yet know whether it will improve patients’ health, how much benefit it might provide or what side effects could emerge.

“This is a moment of tremendous hope, but it is also the beginning of the next scientific chapter,” Randy Gold, president of the ML4 Foundation said.

Gold and his wife, Caroline, helped lead the foundation’s work after their daughter, Eden, was diagnosed with MLIV as a toddler. Eden, now 18, was among the families that helped spur a nearly decade-long effort to move the treatment from laboratory research into a clinical program.

The foundation began prioritizing gene therapy research in 2017. Early work at Massachusetts General Hospital, led by researchers Susan Slaugenhaupt and Yulia Grishchuk, found that the approach corrected neurological dysfunction in a mouse model, according to the foundation. The group also supported a natural-history study designed to document how MLIV progresses over time—information that could help researchers determine whether an experimental treatment changes the disease’s course.

In 2023, the foundation worked with researchers at the University of Massachusetts Gene Therapy Center to complete preclinical studies and prepare the treatment for clinical testing. The program also involved toxicology testing by Charles River Laboratories and production of clinical-grade therapy by Andelyn Biosciences.

Photo: Randy Gold, president of the ML4 Foundation, and his daughter Eden