Oral Glucose Tolerance Test for Mild Cognitive Impairment/Alzheimer's Disease Biomarker Development

UNMET NEED
Alzheimer’s disease is an irreversible, progressive brain disorder that slowly destroys memory and thinking skills, and eventually the ability to carry out the simplest tasks. Treatment of Alzheimer’s disease (AD) is significantly hampered by the lack of easily accessible biomarkers that can detect disease presence and predict disease risk reliably. Early detection biomarkers are necessary not only for the prediction of cognitive decline, but also for patient selection in clinical trials. Often, patients are included in clinical trials whose disease has progressed far beyond modification by therapeutics. Accurate selection of patients will pave the way for effective therapeutics.
 
PROBLEM SOLVED
Researchers at Johns Hopkins and Wake Forest have developed a method for using plasma amyloid-beta (Aβ) as a biomarker to differentiate individuals who have mild cognitive impairment (MCI), Alzheimer’s dementia (AD) or normal cognition, by modulating the plasma Aβ level with oral glucose tolerance test (OGTT).
 
The researchers found that individuals with a brain disease or disorder, such as AD/MCI, have significantly less change (Δ) in plasma compared to controls in both Aβ 40 and Aβ 42. The study data suggest that:

• Oral glucose loading as a plasma Aβ level modular can identify the differences between individuals with MCI/AD versus normal cognitive.
• The method could be used to complement other existing more costly biomarkers such as amyloid PET.
• This method could identify those who are cognitively normal but already be in the early brain stages of AD.
• Reduce costs for AD clinical trials, but more importantly, spare individuals less likely to have AD pathology from undergoing unnecessary tests.
• Widely applicable in the developing world where resources are limited.
• OGTT has a distinct advantage as a safe, noninvasive, cost-effective, and widely available procedure that is already being used in clinical settings world-wide.

 
STAGE OF DEVELOPMENT

• Proof-of-concept pilot studies have been done at Wake Forest and Johns Hopkins School of Medicine.
• 18 AD/MCI and 39 cognitively normal controls underwent oral glucose tolerance testing (OGTT). Blood samples were obtained over a 2-hour period. Changes in plasma Aβ 40 and 42 levels were measured from either baseline or 5 minutes to the 10-minute time-point. 

ASSOCIATED PUBLICATIONS

• Alzheimers Dement (Amst). 2015 Sep;1(3):311-315
• WO 2016134129

Category(s):