$3.2 Million in New Funding Focused on Biomarkers and Moving Toward New Therapies

October 15, 2019

Category: New Grants

The Alzheimer's Drug Discovery Foundation (ADDF) announces five new investments totaling $3,234,725 in funding, including three investments focused on the development of biomarkers and two on novel drug programs.

"Our investment in these biomarker research programs reflects ADDF's steadfast commitment to developing early detection tools for the different pathologies associated with aging, including vascular and inflammation changes in the brain. These biomarker tools are critical, particularly as the field shifts toward more innovative targets for treating Alzheimer’s and related dementias.”

“With these new investments, we are advancing clinical studies and research based on an understanding of the biology of aging.  Our ongoing support of Oryzon Genomics will help advance the development of an epigenetic therapy called vafidemstat, now being studied in a phase 2 trial as a novel therapeutic option for Alzheimer's disease. We are also learning more about rare mutations directly linked to Alzheimer’s through our support of Dr. Roberson, MD, PhD, University of Alabama at Birmingham that may provide a novel therapeutic avenue to targeting excessive brain inflammation.


Our recent biomarker programs look at vascular and inflammation changes. Two of the below biomarker studies used patients from the Mayo Clinic Study of Aging, a large population-based study with well characterized participants.

Clifford Jack, MD, Mayo Clinic Rochester
Cerebrovascular Disease & Clinical Trials in AD: Cognitive Outcomes, Biomarker Outcomes, & Optimal Set of Features
Cerebrovascular disease (CVD) occurs when the arteries and veins that carry blood to and from the brain are disrupted. Since brain cells are highly dependent on a consistent supply of oxygen, any decrease in cerebrovascular health can impair blood flow to the brain and impair cognitive function. CVD is common in cognitively impaired individuals, but it is still not understood how Alzheimer’s and CVD pathologies co-evolve and possibly interact.

In this project, Dr. Jack will use several different neuroimaging approaches that can accurately detect and quantify early cerebrovascular changes in the human brain and relate these changes to cognition and other biomarkers of Alzheimer’s disease. Completion of the work will help clarify how CVD contributes to Alzheimer’s disease and cognitive impairment. In addition, it could help include a vascular component into Alzheimer’s disease diagnosis and help determine which specific CVD neuroimaging markers are needed to optimally inform clinical trial enrollment and outcomes.

Val Lowe, MD, Mayo Clinic Rochester
Targeting Neuroinflammation as a Contributing Pathology in Alzheimer’s Disease Dementia
Inflammation is thought to play an important role in Alzheimer’s disease, but the relationship between neuroinflammation and disease pathology remains unclear. Dr. Lowe and his team hypothesize that subsets of people with mild cognitive impairment or early Alzheimer’s disease have an inflammatory component to their disease. PET imaging is the only way to directly visualize neuroinflammation in a living human brain. Dr. Lowe and his team will use this neuroimaging approach to determine the relationship between neuroinflammation, cognitive changes and inflammatory markers in the blood. This information would help us understand the impact of neuroinflammation on Alzheimer’s disease pathology. Additionally, it could serve as an instrumental biomarker in clinical trials to help inform appropriate therapeutic interventions, determine optimal treatment timing and enrich patient populations for enrollment.

Cerebrospinal Fluid Lipocalin 2 as a Specific Marker of Vascular Dementia
Accurate identification of vascular dementia patients is challenging, and biomarkers are needed to understand what causes it and how to improve diagnosis and the development of treatments. Dr. Llorens and colleagues hypothesize that lipocalin 2, a protein involved in response to bacterial infection, could be used as an accurate cerebrospinal fluid (CSF) biomarker for the diagnosis of vascular dementia. The current funding will enable the team to validate lipocalin 2 in CSF as the first predictive peripheral biomarker for vascular dementia. If successful, lipocalin 2 could serve as an instrumental biomarker in clinical trials to help inform appropriate therapeutic interventions, determine optimal treatment timing and enrich patient populations for enrollment.


Roger Bullock, MD, Oryzon Genomics
ETHERAL: Epigenetic THERapy in ALzheimer’s Disease
Epigenetics determine how much a gene is expressed by altering its expression levels without affecting the underlying genetic code. Epigenetic processes in the brain can become abnormal in response to environmental cues or stress and can have significant effects on genes that control learning and memory, and ultimately neurodegeneration. With several investments from the ADDF, Oryzon Genomics developed a novel epigenetic inhibitor called ORY-2001 that improves memory in preclinical models and is envisaged for the treatment of brain diseases. After a successful Phase 1 clinical trial, Oryzon is now exploring the clinical potential of ORY-2001 in the ETHERAL study, a Phase 2a trial to evaluate its safety and efficacy in patients with mild to moderate Alzheimer’s. The first patient in the trial has already been dosed in Europe. The current ADDF funding will expand the trial to an additional 60 patients, including some based in the US.

Erik Roberson, MD, PhD, University of Alabama at Birmingham
Toward Therapeutic Approaches to TREM2-R47H in Alzheimer’s Disease
A rare gene variant of TREM2 (known as R47H) was recently identified as an important genetic risk factor for Alzheimer’s disease. TREM2 is expressed in microglia, the resident immune cells of the brain. Most of what is known suggests that the TREM2 R47H mutation is associated with excessive inflammation in the brain and may cause microglia to be less responsive in combating Alzheimer’s-linked changes. But there are still major gaps in our current understanding of TREM2.

This proposal harnesses the combined expertise of experts in Alzheimer’s clinical care, microglial biology, and precision medicine to tackle several critical questions about how TREM2 R47H drives increased risk for Alzheimer’s. Dr. Roberson will perform the first comprehensive assessment of TREM2-R47H carriers by characterizing cognitive, neuropsychological, imaging, and biomarker changes in these subjects. The study will also develop novel assays to test the effects of the gene variant on microglial function on patient-derived biospecimen, as well as lay the groundwork to screen for therapies targeted at this rare mutation.