Coenzyme Q10 in Adult-Onset Ataxia

This is a Physician-sponsored pilot study, whose purpose it is determine if high-dose oral
Coenzyme Q10 (CoQ10) is safe and tolerated in patients with sporadic forms of adult-onset
spinocerebellar ataxias (SAOA), a group of degenerative neurological disorders affecting the
cerebellum and pathways to and from the cerebellum, with or without additional central
nervous system (CNS) manifestations, in the absence of family history of degenerative
ataxias.

CoQ10 is an essential cofactor of the electron transport chain and is a potent free radical
scavenger in lipid and mitochondrial membranes. CoQ10 has shown efficacy in treatment of
Parkinson's disease patients, and a Huntington's disease trial gave a trend of slowing down
disease progression (CARE-HD). A small trial of CoQ10 in patients with Friedreich's ataxia
suggested potential beneficial effects on ventricular thickness. CoQ10 is being tested on ALS
patients and is considered to be potentially useful for treatment of Alzheimer's disease.
Thus, CoQ10 is considered to be a promising therapeutic agent that might slow down the
disease progression in a wide variety of neurodegenerative disorders. To date, very high
doses of CoQ10 have not been used in patients with ataxia and the safety and tolerability in
this group of patients should be established before efficacy trials are launched.

Twenty patients with SAOA will be recruited for a double-blind, randomized,
placebo-controlled, multicenter study. Fifteen patients will receive a total of 2400 mg of
oral CoQ10 daily, and five patients will receive placebo, for a period or 4 weeks. Cerebellar
functions will be measured using a validated rating scale (SARA), an oculomotor examination,
and functional measurement of motor function using a 9 hole peg test and timed walk. Safety
labs will be collected and a digital movie will be recorded at the beginning (prior to
treatment with CoQ10) and at the end of the study.

Inclusion Criteria:

1. Diagnosis of SAOA

2. Age 18 or older

3. Adult onset of ataxia

4. Ambulatory capability (with or without an assisting device)

5. Women with 2 years post menopause or surgical sterility or practicing adequate birth
control

6. Stable doses of psychotropic drugs

7. Stable doses of drugs for movement disorders

8. Ability to give informed consent

9. Ability to comply with trial procedures

10. Able to take oral medication

11. No active and significant systemic disease (cardiac, pulmonary, hepatic, renal disease
or cancer) that is not under adequate medical control

12. Women with child-bearing potential who have a negative urine pregnancy test and
practice adequate contraception during the study

Exclusion Criteria:

1. A history or known sensitivity of intolerability to Coenzyme Q10

2. Diagnosis of secondary (non-degenerative) ataxia

3. Family history of degenerative ataxia

4. Diagnosis of childhood-onset ataxia

5. DNA diagnosis of inherited ataxia in the absence of family history

6. Other investigational agent within 30 days of screening

7. Ingestion of Coenzyme Q10 within 120 days of the baseline visit

8. Diagnosis of ongoing malignancy

9. Women who are pregnant or lactating or who have child bearing potential and not using
effective birth control

10. Uncontrolled hypertension

11. Symptomatic orthostatic hypotension

12. Uncontrolled diabetes mellitus

13. Untreated thyroid disease

14. Major psychiatric disease within 12 months of screening

15. History of non-compliance with other therapies

16. Drug or alcohol abuse within 12 months of screening

17. Other condition or therapy that may prevent participation in the opinion of the
investigator