Does Clinical Treatment of Mitochondrial Dysfunction Impact Autism Spectrum Disorder (ASD)?

In this study, 50 children between 3 and 12 years old with formally diagnosed autistic
spectrum disorders (ASD) and also having significant mitochondrial dysfunction will be
treated for a 3 month period with the Mitochondrial Cocktail, a combination of specific
nutritional supplements and metabolite intermediates (including anti-oxidants) and
bio-energy substrates. The Mitochondrial Cocktail is presently widely used as the standard
of care for clinically treating mitochondrial dysfunction.

The precise content of the Mitochondrial Cocktail will be:

- ubiquinol (liquid form, 150 mg/kg subject weight/day

- carnitine, 50 mg/kg subject weight/day

- alpha-lipoic acid, 100 mg/ day.

A series of neurological and psychological evaluations will be conducted by trained
evaluators/clinicians to evaluate both the severity and the clinical presentation of the
ASD/mitochondrial dysfunction with each subject at baseline prior to treatment, after the 3
month treatment and again at 6 months, after another 3 month non-treatment period. In
addition, laboratory investigations will be conducted at the same time-points to assess the
mitochondrial dysfunction and cellular biomarkers thought to be associated with autistic and
mitochondrial disorders. These investigations will include the analysis of samples of blood
and cheek/buccal swabs collected from each child to assess select biochemical markers of
ASD. The Mitochondrial Cocktail treatment will be administered at home preferably in the
morning once a day continuously for a total of 3 months. All the children in the study will
be treated with the same Mitochondrial Cocktail (an open label study). . Safety will be also
evaluated based on the occurrence of adverse events either reported spontaneously by the
subject and/or caregiver or observed by the investigator(s).

Inclusion Criteria:

1. Subject/legal representative is considered reliable and capable of adhering to the
protocol (e.g., able to understand and complete diaries), visit schedule, and
medication intake according to the judgment of the investigator.

2. Subject has a formal diagnosis of autistic spectrum disorders (ASD). the ASD
diagnosis will satisfy the DSM- V criteria for ASD, and will be broad-spectrum
including both severe and milder cases.

3. All subjects will have either suspected mitochondrial dysfunction as assessed by
clinical evaluation, mitochondrial dysfunction as defined by the presence of
significant abnormalities in their buccal mitochondrial respiratory complex
activities (i.e., with either respiratory complex I or complex IV deficiencies) or
have significantly aberrant specific activity ratios. Subjects with significant
deficiencies in either muscle or skin fibroblast respiratory activities will also be
included in those cases if buccal mitochondrial respiratory enzyme activity testing
has not been performed.

Exclusion Criteria:

1. Subject has any medical or psychiatric condition that, in the opinion of the
investigator, could jeopardize or would compromise the subject's ability to
participate in this study.

2. Subject has a medical condition that could be expected in the opinion of the
investigator to interfere with drug absorption, distribution, metabolism, or
excretion.

3. Subject is on a ketogenic or other specialized diet. If the subject was on a
specialized diet in the past, they must be off the diet for ≥2 months prior to the
Baseline Period.

4. Subject has an acute or sub-acutely progressive central nervous system disease.

5. Subject has major brain deformation or severe cognitive dysfunction.

6. Subjects with epilepsy needing to take anti-seizure medications will be excluded.