mitochondrial complex i dysfunction in pws

Conditions: Prader-Willi Syndrome

Summary: prader-willi syndrome (pws) is characterized by profound infantile hypotonia, growth delay, cognitive impairment, muscle weakness and exercise intolerance. studies have suggested that a defect in energy metabolism, yet to be clarified, may be involved in its pathogenesis. many pws patients have received coenzyme q10, but the rationale for this and objective impact on cellular metabolism has not been clarified.

investigators will determine the clinical efficacy of coq10 in a prospective, randomized, double-blind, controlled, cross-over study. primary outcome will include determination of muscle function based on a 3 minute step test which showed good sensitivity in the investigators' pilot study. secondary outcomes will determine effects on muscle power (maximal vertical jump), strength (hand grip), endurance (6 minute walk test), fatigue (pedsql quality of life scale), physical activity level (3dpar), attention (adhdt), cognition (moca), and physical function (chaq). the investigators' subaim is to elucidate the pathophysiologic mechanisms by which clinical improvements are mediated through interrogation of underlying mitochondrial dysfunction to optimize therapies. this will include determination of total aerobic capacity (maximal graded cycle ergometry), muscle metabolic function (31p-magnetic resonance spectroscopy (mrs) of muscle to evaluate high energy phosphagen, anaerobic and aerobic exercise metabolism), mitochondrial function (serum lactate, carnitine, acylcarnitines, lactate/pyruvate ratio), and blood and urine oxidative stress markers of lipid, protein and dna peroxidation. investigators hypothesize that coq10 will lead to a clinically significant improvement in motor function, power, fatigue, habitual activity, attention span \& thereby quality of life in pws.

Eligibility criteria:
inclusion criteria: 1. consent provided 2. patients with genetically confirmed pws aged 13 to 18 years (n=14) 3. ability to cooperate with exercise testing 4. weight \> 35.0 kg 5. in good general health as evidenced by medical history 6. able to take oral medications 7. for females of reproductive potential, use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional 8 weeks after the end of study intervention administration 8. for males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner during study participation and for an additional 8 weeks after the end of study intervention administration exclusion criteria: 1. unable to perform exercise tests, 2. already taking coq10 3. having liver disease or bile duct blockage, 4. having thyroid disease or taking thyroid medications 5. presence of diabetes 6. taking antiarrhythmics or antihypertensives or anti-failure medications 7. presence of gastric disorders 8. presence of skin disorders 9. pregnancy or lactation 10. lactose intolerance 11. known allergic reaction to coq10 or components of preparation. 12. treatment with another investigational drug or other intervention 13. current smoker or tobacco use within 6 months 14. current cannabis user or use within 6 months 15. presence of chronic respiratory disease other than asthma 16. presence of cardiac disease with cardiac insufficiency/chf 17. presence of mr-incompatible metal in body, metal devices or tattoos 18. presence of a bleeding disorder 19. gelatin intolerance 20. clinically significant findings in laboratory tests at screening

Keywords: coq10 muscle function attention span quality of life