Many parents of individuals with Prader-Willi syndrome (PWS) have been faced with ambiguous information about the dietary supplement coenzyme Q10 (CoQ10). There are plenty of anecdotal reports of supplemental CoQ10 providing a great improvement in metabolic function and energy levels, which are so often disrupted in PWS, but also many stories about CoQ10 having little or no impact. We're currently lacking a controlled scientific study of the effects of CoQ10 in PWS, and the associated recommendations on proper dosing.
Dr. Ingrid Tein, an expert in metabolic disorders, received support from FPWR starting in 2016 for such a study — Mitochondrial Complex I Dysfunction in Prader-Willi Syndrome: A New Therapeutic Target — which is badly needed by the PWS community.
We recently had the opportunity to talk with Dr. Tein about her background and unique insights into PWS.
Early Interest in Neurometabolic Diseases
Dr. Tein's two primary interests in college at the University of Toronto were medicine and biochemistry. As a medical student at the University of Toronto, she enjoyed the many subspecialties she was exposed to, but felt a special affinity for neurology, as the study of the most highly evolved tissue in the body (the brain), which is the most intricate and challenging to understand. Along with neurology, she developed a strong interest in neurometabolic diseases. Such disorders occur when there is a disruption in the body's processes to extract energy from nutrients — specifically, energy used for the proper functioning of the nervous system. Dr. Tein appreciated the types of problems associated with neurometabolic diseases. Specifically, she liked the fact that once researchers understand that a metabolic pathway that is "blocked" — i.e., a given enzyme cannot perform its function in the generation of energy in cells — it is possible to identify an alternate pathway and strategic therapy. Dr. Tein also particularly enjoyed working in pediatrics, finding it especially rewarding to interact with children, heal their still-developing nervous systems, and improve their lives and the lives of their families long-term.
Following medical school, Dr. Tein stayed at the University of Toronto for residencies in both pediatrics and pediatric neurology. She then completed postdoctoral fellowships first at the Hopital Necker-Enfants Malades in Paris, and at Columbia University in New York City. During these postdoctoral fellowships, Dr. Tein advanced her knowledge of fatty acid metabolism, i.e., key energy-generating processes in our cells. In Paris, she studied a disorder related to the enzyme Carnitine palmitoyltransferase I (CPT1), known as the "gatekeeper" for fatty acid metabolism, while at Columbia she focused on a disease characterized by a severe deficiency in the uptake of carnitine from the blood — a potentially lethal condition, given carnitine's essential role in generating energy from long-chain fatty acids. Following her postdoctoral fellowships, Dr. Tein returned to Canada, where she is currently an associate professor of pediatrics, laboratory medicine, and pathobiology at the University of Toronto, the director of the Neurometabolic Clinic and Research Lab there, and a Senior Associate Scientist at the Hospital for Sick Children.
Natural Fit with PWS Research
The experiences gained as a postdoctoral fellow continue to inform Dr. Tein's ongoing research on mitochondrial disorders. The mitochondrion is the so-called battery of the cell, processing carbohydrates, fats, and proteins into molecules called adenosine triphosphate (ATP), which store the energy used for the activities of life. Dr. Tein's group specifically studies disorders in fatty acid oxidation — i.e., the mitochondrial generation of energy from fat.
Given her focus on metabolic pathways, and given the known issues with energy and metabolism in PWS, the connections between Dr. Tein's research and the problems of PWS are quite natural. Dr. Tein began thinking seriously about PWS when she treated two infants and one young child for apparent mitochondrial disorders at around the same time. Based on the very low muscle tone (hypotonia) and deficient energy levels in these patients, Dr. Tein prescribed a treatment including multiple vitamins and also CoQ10. Treatment with CoQ10 supplements was indicated based on a muscle biopsy that showed low activity in a particular part of the energy generation cycle in mitochondria. Indeed, CoQ10 plays an important role in transforming nutrients into ATP within the mitochondria. In these cases, supplementation with CoQ10 was extremely effective in remedying low energy levels. Additional genetic testing revealed that these patients all had PWS, highlighting the potential links between PWS and mitochondrial dysfunction.
CoQ10 in PWS: Meeting a Need for Systematic Analysis
At this point, well over a thousand PWS patients worldwide have been treated with CoQ10 supplementation, but there has been no systematic analysis of the quantitative effects of this supplementation on metabolism in PWS. Dr. Tein is uniquely positioned to perform such an analysis for PWS specifically, based on her background in metabolic disorders in general. With support from FPWR, she is implementing the first clinical trial systematically evaluating the effects of CoQ10 in PWS. The trial is designed to be double-blind (neither patients nor researchers know CoQ10 dosing sequence a given patient receives), randomized (patients are randomly assigned a given sequence of CoQ10 dosing), and cross-over (each patient receives a sequence of CoQ10 "on" and "off" dosing, serving as his/her own control).
For the 14 patients aged 13 to 18 years participating in the CoQ10 trial, Dr. Tein and her group will assess the effects of CoQ10 on muscle strength, endurance, and fatigue; cognitive function; and attention. Assessments made during the trial will be based on a variety of blood and urine tests, cognitive function and health assessment questionnaires, and exercise tests. For the trial, Dr. Tein is even using a very specialized bicycle that can be ridden by subjects inside a magnetic resonance spectrometer that collects measures of muscle metabolism! The results of this clinical trial will provide crucial guidance for treating metabolic dysfunction in PWS with CoQ10, and we greatly look forward to its outcomes.
Outside of her work at Sick Kids and the University of Toronto, Dr. Tein is heavily involved in the International Child Neurology Association (ICNA), whose goal is to advance the quality of pediatric neurology care throughout the world. ICNA holds international conferences every 2 years, in various locations around the world, publishes pediatric neurology textbooks, and organizes frequent educational symposia. Dr. Tein has served on the executive board since 2002, and is now in the middle of her term as president (2014-2018).