The potential of a groundbreaking biochemical discovery has been vividly demonstrated in the case of an 8-year-old boy who, after suffering from a rare disease that led to paralysis, is now regaining mobility thanks to an experimental treatment. This remarkable recovery was made possible by neurologists at NYU Langone Health, who administered a novel compound that partially reversed the boy’s rapid decline. Just two months into the treatment, he was able to walk long distances and even run.
The study, published in the journal Nature, focuses on mitochondria, the cell’s powerhouse, where sugars and fats are converted into energy. This process requires coenzyme Q10 (CoQ10), synthesized by human cells. The boy’s condition, known as HPDL deficiency, disrupts CoQ10 production and is one of several mitochondrial diseases affecting thousands nationwide, characterized by paralysis, limb stiffness, and fatigue.
Breakthrough in Treatment
This experimental treatment was rooted in a 2021 study led by Robert Banh, Ph.D., during his postdoctoral fellowship in the lab of Michael E. Pacold, MD, Ph.D., at NYU Grossman School of Medicine. Their research unveiled that CoQ10 synthesis begins when the enzyme HPDL converts 4-hydroxymandelate (4-HMA) into 4-hydroxybenzoate (4-HB), which cells then use to build CoQ10.
Building on this discovery, the Pacold lab demonstrated that both 4-HMA and 4-HB could restore CoQ10 synthesis and mitigate brain damage in mice lacking HPDL. The experimental treatment for the boy was developed after his parents, who had lost two children to the same condition, approached the researchers.
From Lab to Life
Under the guidance of pediatric neurologists Claire Miller, MD, Ph.D., and Giulietta Riboldi, MD, Ph.D., a team of experts secured government approval to treat the boy with 4-HB. The treatment notably reduced the child’s spasticity, a combination of stiffness and paralysis, within two months.
“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,” said Pacold, senior author of the study.
Wider Implications of CoQ10 Research
Beyond rare diseases, CoQ10 levels are known to decrease with age and are linked to conditions like heart disease, diabetes, and Alzheimer’s. Despite the burgeoning market for CoQ10 supplements, less than 5% of ingested CoQ10 is absorbed due to its size and structure, which may explain its limited efficacy in reversing symptoms of HPDL/CoQ10 deficiencies.
The Pacold lab’s research with mice lacking HPDL function revealed that these animals had smaller mitochondria and cerebellums, leading to paralysis. Remarkably, 4-HMA treatment partially reversed these abnormalities, suggesting a critical window in neural development during which CoQ10 precursor treatment is most effective.
Future Directions
NYU Langone Health is now focused on identifying this window and determining the most effective dose for larger studies. The institution owns the intellectual property related to this treatment and is seeking partners to develop CoQ10 intermediates further.
The study’s authors, including Banh, Shi, Riboldi, and Miller, along with other NYU Langone researchers, are exploring the potential of these findings to transform treatments for various neurodevelopmental and mitochondrial diseases.
“Research breakthroughs show their true impact when they change a family’s life,” remarked Alec C. Kimmelman, MD, Ph.D., Dean of the NYU Grossman School of Medicine. “Thanks to an extraordinary team working across our integrated system, we were able to safely and effectively get this treatment from a bench in the lab to a patient in need.”
Conclusion and Next Steps
The serendipitous discovery of this treatment while investigating CoQ10’s anti-cancer potential underscores the importance of cross-disciplinary research. As NYU Langone Health continues to refine this approach, the hope is to offer a viable treatment option for children worldwide suffering from similar genetic conditions.
With ongoing research and potential partnerships, the future looks promising for translating these findings into widespread clinical applications, offering new hope for families affected by rare genetic diseases.
