The Alzheimer's Drug Discovery Foundation (ADDF) announces $2,315,881 in funding for three new research investments—demonstrating its focus to accelerate and advance the use of biomarkers and potential new treatments to change the course of the disease in patients.
"It is exciting to help bring these important research projects to the next level," says Dr. Howard Fillit, Founding Executive Director and Chief Science Officer of the ADDF. "With these new investments, we are addressing the need for the use of biomarkers as a critical tool for diagnosis and disease progression. We are also advancing clinical studies that explore novel therapeutic targets that likely play a critical role in the prevention and treatment of Alzheimer's disease, such as thrombin inhibitors and stress kinase inhibitors."
Paul Worley, MD, Johns Hopkins School of Medicine
Resilience Biomarker NPTX2 and Alzheimer's Disease Progression
Dr. Paul Worley and his team have identified a novel biomarker, termed NPTX2, that may be able to identify patients at risk for cognitive decline. This biomarker distinguishes human subjects with mild cognitive impairment (MCI) or Alzheimer's disease from similarly aged people with normal cognition. NPTX2 is found in the synapses, or neural connections, of brain centers involved in memory. Through a previous ADDF-funded project, Dr. Worley's collaborator, Douglas Galasko developed an assay that can detect NPTX2 in cerebrospinal fluid (CSF) from spinal taps. They showed that MCI and Alzheimer's patients had lower NPTX2 levels in CSF than healthy subjects. In this project, Dr. Worley will test a larger cohort of MCI and Alzheimer's patients and assess NPTX2 levels in CSF samples from patients with other age-related types of dementia. These studies will validate the use of measuring NPTX2 in CSF as a diagnostic tool and biomarker of disease progression in Alzheimer's disease.
Paula Grammas, PhD, University of Rhode Island
Vascular Activation: A Novel Therapeutic Target for Alzheimer's Disease
BEACON is the first clinical study to look into the possible role of the brain's blood vessels in Alzheimer's disease. Extensive research has shown that factors, such as high blood pressure, diabetes, and stroke, injure blood vessels in the brain. This can lead to inflammation that can cause damage or death of brain cells that occurs in Alzheimer's disease. The BEACON Study, based on 30 years of research by Dr. Grammas and her team, repurposes an existing FDA-approved drug, dabigatran, to suppress one part of this inflammation process. They were the first to identify an inflammatory cascade in which injury to the cells lining blood vessels in the brain (known as endothelial cells) "activates" them, causing the release of different molecules harmful or toxic to nerve cells. The one-year trial will test safety and tolerability in Alzheimer’s patients and will measure biomarkers that can provide information on if and how the treatment is affecting disease. If successful, this study could lead to phase 2 clinical trials of dabigatran in Alzheimer's. Results are expected in late 2020.
Manfred Windisch, PhD, NeuroKine Therapeutics
Phase 1 Clinical Trial of a Novel Stress Kinase Inhibitor
Neuroinflammation and the loss of connections between brain cells are hallmarks of most neurodegenerative diseases, including Alzheimer's. MW150, developed by the ADDF's 2016 Goode's Prize winner Dr. Martin Watterson, is a novel therapeutic that targets both of these pathologies. ADDF support of phase 1 studies will make MW150 the first drug in its class to be tested in humans. These first-in-human studies will allow the team at NeuroKine to assess the safety and tolerability of MW150 and gather information on where the drug accumulates in the body. The team will also perform some preliminary analyses on samples from the patients to assess if and how the drug is hitting its intended target. With the successful completion of these experiments, MW150 will be poised to move into larger phase 2 trials.