Abstract
Aim: Defective mitochondrial function and increased oxidative stress have been documented in Autism Spectrum Disorder (ASD) and Phelan-McDermid syndrome (PMS), one of the best-known monogenic forms of ASD. The purpose of this exploratory, double-blind, randomized cross-over trial (RCT) is to verify the efficacy and safety of a “metabolic support therapy” (MST) in PMS, while defining the experimental methodology most apt at maximizing sensitivity and reliability.
Methods: A total of 31 PMS patients completed 4 months of Coenzyme Q10 (50/100 mg b.i.d.) + vitamin E (30/60 mg/d) + polyvitamin B ("active compound") vs. 4 months of only Vitamins E and B ("active comparator"). To explore their sensitivity and reliability, four primary outcome measures were used: VABS, CARS, CGI-I, and VAS. Secondary outcome measures span adaptive behaviors, social cognition, autism, problem behaviors, quality of life (QoL), communication, and comorbidities.
Results: CoQ10+vit. E and B yielded significantly greater improvement in several measures of cognition and adaptive functioning, motor skills, and stereotypic behaviors compared to vit. E and B only. Maternal QoL was especially improved in the presence of CoQ10 (P < 0.004). Time x Treatment interactions in CGI-I and VAS "restricted interests" scores support positive contributions also by vitamins E and B. Side effects, including hyperactivity, insomnia, and irritability, were mild, rare, and did not differ between treatment periods.
Conclusion: MST may produce small-to-moderate improvement, especially in motor skills, social motivation, adaptive behaviors, responsiveness to environmental stimulation, and stereotypic behaviors in up to approximately 70% of PMS patients. A targeted confirmatory RCT contrasting Q10+vit E and B vs. inactive placebo is now warranted.
Reference91 articles.
1. 22q13 deletion syndrome
2. Phelan K, Rogers RC, Boccuto L. Phelan-McDermid syndrome. In M. P. Adam (Eds.) et. al., GeneReviews®. University of Washington, Seattle; 2005. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1198/[Last accessed on 10 Jul 2023]
3. The 22q13.3 Deletion Syndrome (Phelan-McDermid Syndrome)
4. Phelan-McDermid syndrome: a review of the literature and practice parameters for medical assessment and monitoring
5. National Organization for Rare Disorders. Phelan-cDermid sndrome. Available from: https://rarediseases.org/rare-diseases/phelan-mcdermid-syndrome/#affected-populations [Last accessed on 7 Jul 2023]