Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics Study of Bryostatin 1 in Patients With Alzheimer's Disease

Inclusion Criteria: * Male or female, age 50 yrs or older. Females must be of non-childbearing potential (surgically sterilized or at least 2 yrs post-menopausal) * Must have a cognitive deficit present for at least 1 yr \& meet DSM-IV-TRTM criteria for AD \& meet NINCDS/ADRDA criteria for the presence of probable AD * Severity of AD must be mild to moderate, documented with a MMSE score of 12-26 * Has a CT scan or MRI scan within the prior 12 months, which is compatible with a diagnosis of probable AD * Ability to walk, at least with an assistive device * Vision \& hearing sufficient to comply with testing * Normal cognitive \& social functioning prior to onset of dementia * Consistent caregiver to accompany patient to assessment visits * Sufficient basic education to be able to complete the cognitive assessments * Living outside an institution * Informed consent signed \& dated by patient or legal representative * Has provided written authorization for the use \& disclosure of protected health information Exclusion Criteria: * Dementia due to any condition other than AD, including vascular dementia (modified Hachinski Ischemic Scale ≥ 5; positive NINDS-AIREN criteria) * Evidence of clinically significant unstable cardiovascular, renal, hepatic, gastrointestinal, neurological, or metabolic disease within the past 6 months (as determined by medical history, ECG results, chest x-ray, or physical examination) * Use of any drug within 14 days prior to randomization unless the dose of the drug \& the condition being treated have been stable for at least 30 days \& are expected to remain stable during the study \& neither the drug nor the condition being treated is expected to interfere with the study endpoints * Any medical or psychiatric condition that may require medication or surgical treatment during the study * Life expectancy less than 6 months * Any other screening laboratory values outside the normal ranges that are deemed clinically significant by the investigator * Use of an investigational drug within 30 days prior to the screening visit or during the entire study * Significant neurological disease other than AD, including cerebral tumor, Huntington's Disease, Parkinson's Disease, normal pressure hydrocephalus, \& other entities * Major depression according to DSM-IV * Psychotic episodes requiring hospitalization or antipsychotic therapy for more than 2 weeks within the past 10 yrs, not linked to AD * Agitation sufficient to preclude participation in this trial * Alcohol or drug dependence diagnosed within the past 10 yrs * Epilepsy or anti-epileptic drug therapy * Abnormal laboratory tests that might point to another etiology for dementia: serum B12, folate, thyroid functions, electrolytes, syphilis serology * Musculoskeletal diseases that could interfere with assessment * Acute or poorly controlled medical illness: blood pressure\> 180 mmHg systolic or 100 mmHg diastolic; myocardial infarction within 6 months; uncompensated congestive heart failure (NYHA Class III or IV), severe renal, hepatic or gastrointestinal disease that could alter drug pharmacokinetics; blood glucose \> 180 mg/dl on repeated testing at entry into study or need for insulin therapy * Previous randomization in this trial or participation in another investigational trial \< 2 months prior to randomization * Likelihood, according to clinical judgment, of being transferred to a nursing home within 6 months * Change in dosage of any concomitant antidepressant within 30 days prior to randomization * Lack of caregiver * Pregnant or lactating females * Patients who in the judgment of the Investigator may be unreliable or uncooperative with the evaluation procedures outlined in this protocol * HIV positive * Hepatitis B or C positive * Concomitant use of medications other than AD or antidepressant medications for which the dose regimens are stabilized for at least 30 days prior to enrollment in study