Latest news with #MichaelPacold
Time of India
11-07-2025
- Health
- Time of India
8-year-old wheelchair-user walks again after receiving experimental drug for rare and fatal genetic condition
I magine a vibrant 8‑year‑old boy, once an avid runner and a spirited soccer player, confined to a wheelchair by a rare, fatal genetic disease that robbed him of his ability to walk. Traditional CoQ10 supplements offered no relief when his condition rapidly worsened. Then a pioneering experimental drug – 4‑hydroxybenzoate (4‑HB) – designed to bypass his genetic deficiency, not only halted his decline but restored his mobility in just weeks. Within weeks of compassionate‑use treatment approved by the FDA at NYU Langone, he walked again – hiking, go-karting, and playing with renewed vigor. This extraordinary case, the first human success for HPDL deficiency, signals a monumental shift in rare disease therapy, transforming despair into hope. It not only redefines treatment for HPDL deficiency but also shines a beacon of hope for rare mitochondrial diseases everywhere. Read on to know more. From an athlete to being wheelchair-bound : The onset of HPDL deficiency In mid-2023, this otherwise healthy boy – a competitive runner and soccer enthusiast – started showing worrying signs: stumbling, ankle stiffness, and loss of coordination. He began experiencing involuntary muscle contractions in his ankles while playing soccer. Within months, these symptoms escalated; by November, he needed a wheelchair and struggled even to stand. Genetic testing at NYU Langone revealed biallelic mutations in the HPDL gene, essential for producing coenzyme Q10 (CoQ10), a vital antioxidant for mitochondrial health. HPDL deficiency disrupts the CoQ10 biosynthesis pathway, impairing cellular energy production. Without CoQ10, neurons and muscles lose function, leading to spasticity, paralysis, seizures, and often early death, with severe forms manifesting in infancy. In this child's delayed-onset case, symptoms appeared later but progressed swiftly. The CoQ10 conundrum: Why supplements aren't enough CoQ10 is widely available as a dietary supplement and is generally safe. However, CoQ10 supplements are completely ineffective in HPDL cases affecting the brain because CoQ10 molecules are too large and hydrophobic to cross the blood–brain barrier. Without reaching the brain, supplemental CoQ10 offered minimal benefit, essentially leaving the underlying condition unchecked. While CoQ10 supplements may help peripheral tissues, they leave neurological symptoms – spasticity, paralysis, and rapid degeneration – untreated. A biochemical breakthrough: Smart 'tailor-made' solution In 2021, researchers at NYU, led by Dr. Michael Pacold, discovered that HPDL catalyzes an early step in CoQ10 synthesis: converting 4‑hydroxy‑methyladenine (4‑HMA) to 4‑hydroxybenzoate (4‑HB), a precursor that is small and hydrophilic enough can cross the blood–brain barrier. In HPDL-deficient mice, oral 4‑HB restored CoQ10 production, significantly improved neurological function, and rescued 90% of subjects when administered early. Translating this from mice to humans presented risks, but given the rapid deterioration and the absence of other options, the child's parents and medical team pursued a compassionate-use approval from the FDA. Compassionate use in humans: Life-changing progress By November 2023, with the boy's condition worsening and time running out, NYU's team – led by Dr. Claire Miller – obtained FDA approval for single-patient investigational use of 4‑HB. The treatment began in December 2023. In July 2024, the boy began daily oral doses of 4‑HB dissolved in water. Initial mood and side effects varied – he experienced nausea occasionally – but the potential benefits were undeniable. Remarkably, within just a month, he regained the ability to walk and walked more than half a mile in Central Park. His progress was profound. Over the next year, he completed a four‑mile hike and even enjoyed go-karting – all without serious side effects. Doctors report a significant restoration of motor function and stamina. The boy can complete his daily activities without assistance—though rigorous sports remain off-limits. There have been no severe side effects reported so far. Impact and perspective: A medical breakthrough This case represents the first successful application of 4‑HB therapy in a human with HPDL deficiency. Classified by experts as a "bench-to-bedside" success, it demonstrates how basic biological insights – like metabolic pathways – can be translated into transformative therapies. Pacold highlighted the value of NIH-funded foundational research: without it, 4‑HB's pathway to human use wouldn't exist. However, experts emphasize that while the results are unprecedented, caution remains essential. One patient's outcome isn't enough to define safety or efficacy broadly. Nevertheless, the experimental treatment offers proof-of-principle and has prompted plans for larger clinical trials across ages and HPDL variants. Broader implications for rare disease care This case highlights the potential of precision, mechanism-based therapies for ultra-rare genetic disorders – many of which lack approved treatments due to their complexity and small patient populations. It also illustrates how compassionate-use pathways can bridge the gap between preclinical research and patient care. For HPDL deficiency, this success sets the stage for larger clinical trials. Researchers are now exploring the treatment's wider applicability and grappling with whether 4‑HB acts solely by restoring CoQ10 or if other mechanisms are at play. A beacon of hope for rare disease communities Rare genetic disorders often lack effective therapies due to low patient numbers and complex biology. This milestone highlights how customized, mechanism-based interventions can break new ground. It reiterates the importance of NIH-funded basic science – Pacold's pathway elucidation stemmed from foundational grants. Dr. Miller reflected on how 'movement is identity and personality,' and described the turnaround as 'heartwarming.' As the boy himself reportedly asked, "When are you going to make this a pill?" – a reminder of evolving patient-driven optimism. Looking ahead What's ahead now? Next steps focus on clinical expansion: enrolling more pediatric patients, refining dosing, and assessing long-term outcomes. Scientists also aim to clarify whether 4‑HB works solely by boosting CoQ10 or also via unexpected mechanisms. Additionally, assessing whether similar treatments can address broader CoQ10 deficiencies is a promising, yet cautious, discussion. This is how Aryan Khan spent the money in jail that he received from his father Shah Rukh Khan: Reports
New York Post
10-07-2025
- Health
- New York Post
8-year-old whose rare condition put him in a wheelchair can walk again — thanks to an experimental drug made just for him
An eight-year-old boy has regained his ability to walk with the aid of a compound found in a common over-the-counter supplement. The boy's case was detailed in the journal Nature. The unnamed child was an active athlete until the summer of 2023, when he began to struggle with mobility. Within months, his symptoms progressed to the point that he required a wheelchair. 'Our son's condition dramatically changed in a short period. He went from being the fastest runner in his class and an avid soccer player to struggling just to walk, often limping and experiencing frequent falls,' the boy's parents, who wish to remain anonymous, said to STAT News. 3 Their son was eventually diagnosed with HPDL deficiency, a rare genetic condition that inhibits the body's ability to produce sufficient levels of coenzyme Q10 (CoQ10), a compound critical to cell function. Prostock-studio – Their son was eventually diagnosed with HPDL deficiency, a rare genetic condition that inhibits the body's ability to produce sufficient levels of coenzyme Q10 (CoQ10), a compound critical to cell function. HPDL deficiency occurs when an individual inherits two mutated versions of the human HPDL gene, which is used in the production of the CoQ10 enzyme. Without adequate CoQ10, patients struggle with muscle control, walking, and are at a higher risk of seizures. When HPDL deficiency surfaces later in adolescence, it manifests as muscle weakness and stiffness in otherwise healthy children. The boy in question was placed on a protocol of CoQ10 supplements — but the pills could only help to a certain extent, as the enzyme is too large to cross the blood-brain barrier. '[CoQ10] is safe. It's reasonably effective at treating symptoms outside of the brain, but almost completely ineffective at treating symptoms within the brain, because it doesn't get through the blood-brain barrier,' Michael Pacold, an associate professor of radiation oncology at NYU Langone and one of the study authors, told STAT. But 4-HB is a building block of CoQ10 — and, helpfully, it's thin enough to cross the blood-brain barrier and can be condensed into a powder that is dissolved in a water solution. 3 CoQ10 is available as an over-the-counter supplement to help boost energy and combat fatigue. luchschenF – The FDA has not approved CoQ10 or 4-HB as a treatment for any specific disease or condition. However, CoQ10 is available as an over-the-counter supplement to help boost energy and combat fatigue. While 4-HB is not approved by the FDA, with the consent of the boy's parents and the insistence of his doctors, the FDA approved its use as a single-patient investigational drug — in other words, doctors were permitted to use an unapproved drug for a specific patient to treat a specific condition. 'It was one of the hardest decisions we've ever made [to try the experimental treatment], but doing nothing felt riskier,' said the boy's parents. 'We saw how quickly our son was declining and knew we had to act. After speaking with doctors and doing our research, we got hope and confidence to step into the unknown.' 3 Within a month of receiving treatment, the boy was walking again and even completed a nearly mile-long trek across Central Park. maxximmm – A 2021 study tested 4-HB on mice with HPDL deficiency and found that the supplement restored mobility in rodents. Its use in the case of the eight-year-old body is the first time it's been used to treat the condition in humans. After stopping his CoQ10 supplements, the boy began taking a 4-HB supplement in a 600ml solution. Equivalent to nearly three glasses of water, the liquid cure often caused him to vomit. This was eventually reduced to a 300ml solution, or just over one glass of water. However, the upchuck was worth the upturn, as within a month of receiving treatment, the boy was walking again, and even completed a nearly mile-long trek across Central Park. Researchers are hopeful the success story will serve as a beacon to others. The research team is calling it a medical breakthrough. 'We all dream of this as scientists. And every morning I pinch myself … is this really a dream?' said Pacold. Now, Pacold and his team are working on a larger study to test the approach on a larger group of children.
