An 8-year-old boy with a rare, often fatal mitochondrial disease has shown remarkable recovery after receiving an experimental treatment developed by researchers at NYU Langone Health. The child, who rapidly declined from playing sports to requiring a wheelchair within months, can now walk long distances and run again following treatment with a novel CoQ10 precursor compound.
The case, published July 9 in Nature, represents the first successful demonstration that neurological symptoms of primary CoQ10 deficiency can be stabilized or improved by supplying CoQ10 precursors rather than the coenzyme itself. The treatment targets HPDL deficiency, a rare condition that prevents cells from producing coenzyme Q10 (CoQ10), an essential antioxidant required for mitochondrial energy production.
Rapid Disease Progression Reversed
The patient's condition deteriorated with alarming speed. In August 2023, he was running and playing soccer normally. By September, involuntary muscle contractions affected both ankles. By October, he had lost the ability to run and play sports, and by November, frequent falls necessitated a wheelchair. Genetic testing confirmed he carried two mutant copies of the HPDL gene, the same condition that had killed two of his siblings in infancy.
"They were so scared when we met," said Dr. Claire Miller, a pediatric neurologist specializing in movement disorders at NYU Langone Health. At their November 2023 meeting, the child couldn't cross the hospital lobby without falling, and his condition worsened noticeably from week to week.
Scientific Foundation in Mouse Studies
The experimental treatment emerged from research led by Dr. Michael Pacold, assistant professor in the Department of Radiation Oncology at NYU Grossman School of Medicine. His team's 2021 study revealed that HPDL enzyme converts 4-hydroxymandelate (4-HMA) into 4-hydroxybenzoate (4-HB), which cells then use to build CoQ10's essential components.
In mouse studies, animals engineered to lack HPDL function typically developed severe seizures and died within 15 days of birth. However, when treated with 4-HMA or 4-HB, more than 90% of the mice survived to adulthood and moved near normally, instead of becoming paralyzed and dying.
"His data was incredibly convincing to me," Miller said of Pacold's findings. The mouse results showed both efficacy and safety, with treated animals living upward of 18 months with only limited neurological symptoms like paw weakness.
Regulatory Approval and Treatment Protocol
When the boy's parents approached the research team, a multidisciplinary group quickly assembled to secure regulatory approval. The team included members from NYU Langone's Office of Science and Research, Regulatory Affairs, Technology Opportunities and Ventures, the Office of General Counsel, and the Conflicts of Interest Management Unit.
The FDA granted approval under expanded access provisions, which allow physicians to use experimental treatments for life-threatening diseases when no other options exist. With subsequent approval from NYU Langone's Institutional Review Board, treatment began in December 2023.
The patient received daily doses of 4-HB dissolved in water. According to the child, the medicine tastes sour but is more palatable when cold. Within a month, he could walk more than half a mile through Central Park with his family.
Clinical Outcomes and Recovery
Two months after beginning treatment, the boy demonstrated remarkable improvement. He could walk long distances and even run, representing a dramatic reversal from his wheelchair-bound state just months earlier. The recovery was partial, with some spasticity and gait issues remaining, but the functional improvements were substantial.
"Even small improvements — like walking more easily or having more energy — mean a lot," the family told Live Science. "It's reassuring to know the treatment is making a difference."
Currently, the child can perform nearly all daily functional activities independently except sports. He has joined his family on a 4-mile hike and operates go-kart pedals by himself, demonstrating continued strength and energy improvements.
Advantages Over Traditional CoQ10 Supplementation
The treatment addresses a fundamental limitation of CoQ10 supplementation. Despite a dietary supplement industry expected to represent a billion-dollar market within a decade, less than 5% of ingested CoQ10 reaches the body due to its structure and size. The compound is poorly absorbed in the gut, with even less crossing the brain's protective barrier due to its large, hydrophobic nature.
"To our knowledge, this is the first demonstration that neurological symptoms of a primary CoQ10 deficiency can be stabilized or improved by supplying not CoQ10 itself, but instead its smaller, more easily processed precursors, which cells then use to build more of the coenzyme," said Dr. Pacold, senior author of the Nature study.
Treatment Window and Future Research
The research suggests a critical treatment window exists during neural development when HPDL deficiency effects are most reversible with CoQ10 precursor treatment. The clinical team theorizes that the treated child retained some HPDL function, allowing normal development until a certain stage before symptoms emerged.
Children with HPDL deficiencies show varying disease severity depending on their specific genetic mutations, ranging from complete loss of function (fatal) to partial function levels. The team's mouse data indicate that after a certain developmental point, treatment effectiveness diminishes significantly.
"The immediate next step is to try to get this into more patients with this disease and establish whether or not the response that we saw in this child is typical," Pacold emphasized.
Broader Implications
Beyond rare diseases, cellular CoQ10 supplies naturally decrease with aging and in conditions including heart disease, diabetes, and Alzheimer's disease. The discovery occurred serendipitously while the Pacold Lab investigated anticancer potential of targeting CoQ10 production, when they observed that CoQ10 precursors caused recovery from neurodegenerative processes in animal models.
However, questions remain about the exact mechanism of action. Professor Siegfried Hekimi from McGill University, who was not involved in the research, noted that while the findings suggest restored function in both mice and humans lacking HPDL, it's unclear whether improvements relate directly to restored CoQ10 levels or other mechanisms.
The research team plans to expand studies to more patients with HPDL deficiencies and potentially broader groups with related CoQ10-affecting conditions. NYU Langone owns the intellectual property for the treatment, which the institution and Dr. Pacold are seeking to license for further development.
Dr. Pacold received the Pershing Square Foundation's "MIND" Prize in April, providing $750,000 to support continued research. The work represents a successful example of translating laboratory discoveries into clinical applications through NYU Langone's integrated research and clinical system.
