This is a Phase I clinical study to assess the safety, tolerability and biologic activity of in vivo AAV-mediated delivery of CERE-110. Six subjects will receive CERE-110 in dose-escalating fashion. All subjects will receive bilateral, stereotactic injections of CERE-110 for a total of four injections to target the basal forebrain region of the brain containing the nucleus basalis of Meynert (NBM). Two doses will be administered to each of three subjects in an open-label manner. A four-week observation period will be implemented after each subject within a cohort is dosed. Three months from the time that the last subject in the first dose cohort has been dosed, escalation to the next dose will proceed if CERE-110 has been shown to be safe. All study participants will be observed for a 24-month period and then followed annually.

Ages Eligible for Study:  50 Years   -   80 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• Alzheimer’s disease as determined by NINCDS/ADRDA criteria.
• Score of ≤ 4 on a modified Hachinski Ischemia Scale
• Mini-Mental State Exam (MMSE) score in the range of 16 to 24
• No significant neurological or medical abnormalities contraindicating surgery, MRI/PET imaging or study participation
• Subjects stable on standard-of-care medications (i.e., acetylcholinesterase inhibitors) for Alzheimer’s disease for 3 months prior to entry
• A Hamilton Depression Scale score of ≤ 12 on a 17-item scale and no history of major depressive episode within the last 2 years
• A score of < 15 on the Beck Depression Inventory
• Adequate visual and auditory acuity to allow neuropsychological testing
• Normal serum B12, thyroid function tests, and negative syphilis antibody test
• The informed consent document must be signed by both: a competent and willing subject, and a surrogate identified by the participant, or a legally authorized power of attorney for Health Care, or a family member

Exclusion Criteria:

• History of cancer within the last five years, except superficial basal or squamous cell skin cancer or cervical carcinoma in situ
• History of alcohol abuse or dependence within the last two years
• Liver serum transaminases (AST and/or ALT) > 5 times the upper limit of normal; total and/or direct bilirubin > 1.5 mg/dL, hemoglobin < 9mg/dL; PT and PTT > 2 times the upper limit of normal; creatinine clearance < 30 mL/min; positive serology for HBV or HCV; absolute neutrophil count < 1,500 cells/mm3 and a platelet count < 100,000/mm3
• Any significant systemic illness, unstable or severe medical condition(s) that could put the subject at risk during the study, interfere with outcome measures or affect compliance with the protocol procedures
• Centrally active beta-blockers, anti-Parkinsonian medications, psychostimulants, antipsychotics, neuroleptics, or narcotic analgesics, long-acting benzodiazepines or barbiturates, hypertensive agents with a CNS effect, short-acting anxiolytics or sedative hypnotics more frequently than two times per week within 14 days of screening, herbal products for Alzheimer’s disease, antidepressants with significant cholinergic side effects (e.g., tricyclics), initiation or change in dose of standard treatment for Alzheimer’s disease
• Other medication with significant cholinergic or anticholinergic side effects
• Warfarin (coumadin), nonsteroidal anti-inflammatory drugs, aspirin, Prozac, or Ginkgo biloba within 14 days of surgery
• Subjects who have received investigational agents or been exposed to investigational devices for 30 days prior to enrollment
• Subjects with a history of receiving gene transfer products of any kind