The Alzheimer's Drug Discovery Foundation (ADDF) awarded three new investments that focus on prevention, including support of the HOPE4MCI Phase 3 trial.
"It is exciting to support a novel idea that has advanced this far," says Dr. Howard Fillit, founding executive director and chief science officer of the ADDF. "Dr. Gallagher's research could yield the first drug to slow progression of amnestic mild cognitive impairment, altering the course of Alzheimer's disease and restoring normal brain function.
"The other two investments build on the wealth of knowledge that we are gaining in area of prevention and will arm clinicians and individuals with better information on reducing risk."
Michela Gallagher, PhD, Johns Hopkins University and founder of AgeneBio
4th Annual Goodes Prize for Excellence in Alzheimer's Drug Discovery: Imaging Sub-Study for the HOPE4MCI Phase 3 Trial
People with amnestic mild cognitive impairment (aMCI) have more memory problems than expected for their age. While their symptoms are not as severe as patients with Alzheimer's, they are at increased risk for developing dementia. Dr. Gallagher's research at Johns Hopkins provided the first scientific evidence for developing therapies that target hyperactivity in brain cells, especially in aMCI patients when hyperactivity is most pronounced. Dr. Michela Gallagher founded AgeneBio to tackle hyperactivity in the brain's memory center in patients with aMCI by repurposing a formulation of the FDA-approved epilepsy drug levetiracetam.
HOPE4MCI, a pivotal phase 3 clinical trial with their drug AGB101, is currently underway. With funds from the ADDF's Melvin R. Goodes Prize, Dr. Gallagher will be able to acquire a new set of imaging data using high resolution MRI and tau PET scans. These data will provide sensitive and quantitative measures for the trial and determine if lowering hyperactivity slows the progression from MCI to mild dementia in Alzheimer's patients.
ADDF has supported AgeneBio's discovery stage and clinical trials since 2010 with over $2.5 million in grant funding. With the recently launched Phase 3 trial for AGB-101, this is the most advanced program in the ADDF portfolio.
Kejal Kantarci, MD, MS, Mayo Clinic
Effects of Early Menopausal Hormone Therapy on Imaging Biomarkers of Cognitive Health
Many studies have associated the use of menopausal hormone therapy with a lower risk of dementia and cognitive decline. However, clinical findings have been mixed and suggest that neuroprotective benefit may depend on many factors including the timing of treatment and type of hormone therapy.
Dr. Kantarci will be performing a 12-year follow up of the Kronos Early Estrogen Prevention Study (KEEPS), a nationwide clinical trial that tested two different menopausal hormone therapies in newly postmenopausal women. This study provides a unique opportunity to clarify the long-term effects of menopausal hormone therapies on cognitive health and Alzheimer's risk based on the initial trial. Add-on funding from the ADDF will support brain imaging of tau, another Alzheimer's marker. Findings from this study will inform whether postmenopausal women should take hormone replacement therapy and which kind is most protective for brain health.
Phillip Tully, PhD, MPsych, University of Adelaide
Minimizing Blood Pressure Variability with Antihypertensive Drugs to Reduce Dementia Risk: An Individual Participant Data (IPD) Meta-Analysis of Cohort Studies in the CAPA Consortium
Elevated blood pressure in mid-life is a modifiable risk factor for cerebrovascular and Alzheimer's disease. However, recent studies have indicated that blood pressure fluctuations (blood pressure variability) may be more important than mean blood pressure in predicting future risk of cerebrovascular disease. Importantly, certain blood pressure medications may better control blood pressure-variability than others. Dr. Tully will make use of ADDF's Consortium of Cohorts for Alzheimer's Prevention Action (CAPA) to pool together individuals from 10 cohorts with over 50,000 patients to study whether certain classes of anti-hypertensive drugs are better able to control blood pressure-variability and whether these drugs also reduce the risk of dementia later in life. These cohorts contain data for cognitive function, dementia status, and imaging data. Findings from this study will determine whether certain classes of anti-hypertensives are better able to reduce blood pressure-variability, cerebrovascular disease, and dementia risk. This will allow doctors to prescribe anti-hypertensives that will most reduce Alzheimer's risk later in life.