271196 Prevention of Alzheimer's disease through drug intervention: Design of quantitative biomarker monitoring protocol

Sunday, October 28, 2012

Cherise Charleswell, MPH , Magnetic Resonance Spectroscopy Unit, Huntington Medical Research Institute, Pasadena, CA
Thao Tran, BA, ARMRIT , Magnetic Resonance Spectroscopy Unit, Huntington Medical Research Institute, Pasadena, CA
Michael Miller, PharmD , Pharmacy, Webster Pharmacy, Altadena, CA
Brian Ross, MD, PhD, FRCS, FRCPath , Magnetic Resonance Spectroscopy Unit, Huntington Medical Research Institute, Pasadena, CA
Background: Alzheimer's Disease, the commonest form of dementia poses a large burden to caregivers, public health systems and physicians. This Abstract concerns the design and implementation of a clinical drug trial to be guided by novel, non-invasive biomarkers of the disease. Approach and Methodology: A Repurposed drug, minocycline, a second generation tetracycline is used to reverse neuronal loss and inhibit neuroinflammation. Number of patients = 80; Drug 50mg by mouth for 6 months. Safety blood urea and liver function tests. Open label trial for N=12 Measures: neuropsychological exam (RBANS); MMSE; quantitative MRI (hippocampal volume) magnetic resonance spectroscopy of brain (N-acetyl aspartate; myoinositolNAA/mI) repeat measures monthly. Results: Preliminary results from 12 subjects (AD = 4; amnestic mild cognitive impairment (aMCI) =1; Normal elderly =7. MMSE and RBANS readily distinguished while hippocampal volume (normal range 6.6 – 8.8cm3) defined AD + aMCI vs Normal. Most striking was the novel MRS biomarker pair NAA/mI (Normal range =2.1 – 2.6) which not only confirmed clinical, neuropsychology and QMRI but allowed detection of a drug response within 1 month in 3/12 subjects. Conclusions: Problems and Solutions: Promising diagnostic tools permit study of novel Alzheimer drug therapies using smaller numbers of patients. Promising preliminary ‘open label' without placebo must be discounted. A Clinical Trial Consultant advises 3:1 drug-placebo blind study. Pharmacist will compound Minocycline placebo. ‘Power” calculation indicates that N=12 patients may suffice in the planned double blind trial. Future: Novel FDA approved anti neuroinflammatory drugs evaluated using the present Protocols.

Learning Areas:
Basic medical science applied in public health

Learning Objectives:

Presenting author's disclosure statement:

Qualified on the content I am responsible for because: I am a current Graduate Student with a professional background in health administration and the development and coordination of clinical trials, using both repurposed drugs and investigational new drugs. My current interests have focused on the elderly population and the neurological disorders of Alzheimer's Disease and dementia.
Any relevant financial relationships? No

I agree to comply with the American Public Health Association Conflict of Interest and Commercial Support Guidelines, and to disclose to the participants any off-label or experimental uses of a commercial product or service discussed in my presentation.