Children with Prader-Willi syndrome suffer from very low muscle tone, growth delay, short stature, developmental delay, muscle weakness and exercise intolerance. Studies have suggested that there is a problem with energy metabolism in PWS but what kind of problem this is and how this leads to PWS is not clear at the present time. Many PWS patients have received Coenzyme Q10 but the reason for this is also unclear. We have made a new discovery in 3 children with PWS who we have shown to have a deficiency in the battery (mitochondria) of the cell that generates energy for all tissues including the brain for cognitive development, the muscle for power and exercise endurance and the body for overall growth. We have also shown evidence of a muscle disorder in PWS by examining the muscle under a microscope. This may be contributing to the low tone in PWS. Children with mitochondrial dysfunction may have all of the clinical problems mentioned above and thus this dysfunction may be responsible in part for many of the features in PWS and provides a new target for treatment in PWS. This defect is also associated with the production of excessive free radicals which lead to oxidative stress and tissue injury. One of the important treatments for mitochondrial dysfunction is Coenzyme Q10 which facilitates increased energy generation from the mitochondria. CoQ10 also acts as an important antioxidant in the cell, thereby decreasing the injury from free radicals. Some but not all patients with PWS have been shown to have low CoQ10 levels which would decrease energy generation. Many PWS patients have received CoQ10 supplements, but the effect of this supplement on cell metabolism has not been formally studied to this point in time.
We plan to carefully study the effect of CoQ10 in adolescents with PWS using objective scientific measures. We will determine the effect of CoQ10 on motor function as well as on power, strength, fatigue, physical activity level, attention span, physical function and quality of life using specific exercise tests and questionnaires. We also plan to determine the mechanisms by which the clinical improvements occur by investigating the mitochondrial dysfunction so that we can develop better therapies. This will include determining total aerobic capacity using our stationary bicycle, and measuring the chemicals in the exercising leg muscle noninvasively with our advanced MRI magnet where patients exercise on a bicycle inside the magnet. We will also measure certain chemicals in the blood and urine that will tell us how well the mitochondria are working and how much they are generating toxic free radicals. We predict that CoQ10 will lead to an important improvement in muscle function, power, fatigue, activity level, and attention span by improving the function of the mitochondria thereby significantly improve the quality of life in individuals with PWS.
This project was funded by the Foundation for Prader-Willi Research Canada
Ingrid Tein, MD
The Hospital for Sick Children, Toronto, Canada