Safety and Tolerability of Antioxidant (AT-001)for Reducing Brain Oxidative Stress

Placebo-controlled, single-center, multiple ascending dose study. Approximately 8 healthy
volunteers will be enrolled into 3 sequential cohorts, for a total of 24 enrolled subjects.

All subjects will be treated with study drug or placebo for 12 weeks. Subjects will be seen
in the clinic for the following visits: Screening, Baseline (Day 1), Day 2, Day 4, Day 7
(Week 1), Week 2, Week 4, Week 6, Week 8,and Week 12 while on study drug. An additional
safety visit at Week 14 (two weeks after study drug discontinuation) will be required of
study participants.

Subjects will undergo blood draws, urine collection, assessment of vital signs, and review of
Serious Adverse Events (SAEs) and Adverse Events (AEs) as well as changes in concomitant
medical conditions and medications at every visit.

Routine medical examinations will be performed at study screening and enrollment, Week 1,
Week 2, Week 4, Week 6, Week 8, Week 12, and Week 14 visits.

MRI will be performed on all subjects at Screening to ensure safety of lumbar puncture.
Research procedures will also include lumbar puncture at the Screening and Week 12 visits.

A designated Data Safety Monitoring Board (DSMB) will evaluate safety in the subjects who
have been enrolled and completed a cohort before escalating to the next cohort. The DSMB will
review safety data (i.e. any AE or SAE) through Week 14. The committee may also request to
review additional data.

The DSMB will also be convened in the event of a dose limiting toxicity (DLT) to determine
whether stopping rules for accrual have been met.

Inclusion Criteria:

- Men and women age > 64 years.

- Not demented by Hachinski Ischemic Index (≤ 4)

- English-speaking, to ensure compliance with study visit procedures.

- Female participants must not be pregnant or of childbearing potential, i.e. either
surgically sterile or postmenopausal for > 1 year.

- Stable medical condition for three months prior to screening visit, with no clinically
significant abnormalities of hepatic, renal, and hematologic function defined as
follows: WBC within normal limits, platelets > 100,000, hemoglobin ≥11 mg/dL, srum
creatinine ≤ 1.8 mg/dL, AST or ALT ≤ 1.5 ULN, no clinically significant abnormalities
of other laboratory studies (CBC, chemistry panel, urinalysis).

- Non-diabetic confirmed by fasting serum glucose <126 mg/dL and on no oral hypoglycemic
agents or insulin treatment.

- Stable medications for 12 weeks prior to screening visit.

- Able to ingest oral medications.

- No contraindication to baseline MRI (metallic implants, pacemakers, shrapnel…etc.).

- Physically acceptable for this study as confirmed by medical history, physical exam,
neurological exam and clinical tests.

Exclusion Criteria:

- Significant neurologic disease such as Parkinson's disease, stroke, brain tumor,
multiple sclerosis or seizure disorder.

- Major depression in past 12 months (DSM-IV criteria) major mental illness such as
schizophrenia, or recent (in past 12 months) alcohol or substance abuse.

- History of invasive cancer within the past two years (excluding non-melanoma skin
cancer).

- Contra-indications to lumbar puncture (bleeding disorder, platelet count < 100,000,
anticoagulant treatment, major structural abnormality or sepsis in the area of the
lumbosacral spine, previous lower back surgery that would make LP technically
difficult, hypersensitivity to lidocaine).

- Other conditions that will contribute to oxidative stress including but not limited to
current smokers of cigarettes or cigars (within past month), history of alcohol or
drug abuse as determined by medical history review.

- Known sensitivity, intolerance, or allergies to yeast or selenium-based compounds.

- Daily intake of more than 75 µg selenium/day (US RDA) in the 90 days prior to
enrollment.

- Use of any investigational agents within 90 days prior to screening.

- Major surgery within eight weeks prior to the Baseline Visit.

- Severe unstable medical illnesses, including uncontrolled cardiac conditions or heart
failure (New York Heart Association Class III or IV).

- Extremes of body weight (<100 or >240 lbs) to exclude upper and lower 5th percentiles
for age that may influence PK and safety data.

- Residence in a skilled nursing facility.

- Blindness, deafness, language difficulties or any other disability that may prevent
the subject from participating or cooperating in the protocol.

- Safety laboratory values deemed clinically significant by investigator.

Excluded Medications:

- Experimental drugs.

- Coumadin or heparin.

- Insulin or other hypoglycemic agents.

- Supplements containing more than 75 µg selenium/day (US RDA) in the 12 weeks prior to
enrollment.

- The maximum dose of vitamin E (α-tocopherol) permitted in supplements will be 400
IU/day, vitamin C 1000 mg/day.