More than $11 Million in New ADDF Investments Support Diverse Drug Targets and a Range of Biomarkers

The Alzheimer’s Drug Discovery Foundation (ADDF) announced 11 new investments from October 2020 to March 2021, totaling more than $11 million supporting innovative Alzheimer’s drug discovery and biomarker research. The latest round of investments includes research in academic medical centers across the United States, at biotech companies both here and abroad, and by the Foundation for the National Institutes of Health, a Congressionally established charitable organization that creates and leads public-private alliances to advance breakthrough medical discoveries.

“I am inspired by the quality and diversity of the research being led by the innovative scientists in our latest round of funding,” said Dr. Howard Fillit, ADDF Founding Executive Director and Chief Science Officer. “In addition to our two investments in drug discovery, today we announce nine investments in platforms for brain imaging, digital testing and CSF and peripheral biomarkers—including eye scans and blood tests, that will improve drug discovery research by ensuring clinical trials are enrolling patients with the pathology targeted by the drug being tested, for example tau tangles, and giving investigators a way to monitor patient progress.”

DRUG DISCOVERY

Miranda Orr, Ph.D., Wake Forest University Health Sciences
Phase 2 Clinical Trial to Evaluate the Safety and Feasibility of Senolytic Therapy in Alzheimer's Disease
$3,000,000

Dr. Orr and colleagues have identified medications that selectively target senescent cells. Senescent or “zombie cells” are more common with aging and may contribute to the development and progression of Alzheimer’s. The teams’ medications, called senolytics, cleared toxic senescent cells, reduced disease pathology and improved overall brain structure and function in mice and improved their performance on learning and memory tasks. The drugs were well tolerated in healthy humans in phase 1 trials, where they were also shown to reduce senescent cells and improve physical function. The research is moving to its first phase 2 randomized, placebo-controlled study in individuals with prodromal, or early, Alzheimer’s disease.

Dirk Beher, Ph.D., Asceneuron SA
A Single-Center, Randomized, Placebo-Controlled Single and Multiple Ascending Dose Study in Healthy Male and Female Subjects to Study the Safety, Tolerability, Food Effect, Pharmaco-kinetics and Target Engagement of the Second-Generation O-GlcNAcase Inhibitor ASN121151
$2,200,000

One of the hallmarks of Alzheimer’s disease is the correlation between accumulation of tau tangles in the brain and progression of Alzheimer’s symptoms. Dr. Beher and his colleagues have developed a drug that inhibits an enzyme called O-GlcNAcase, which disturbs the normal function of tau, allowing it to build up in the brain. This investment supports the first investigation of their drug, ASN121151, in healthy volunteers to test its safety and tolerability. They will also study how the body absorbs, distributes, and eliminates the drug and how much of the drug binds to the O-GlcNAcase enzyme in the living human brain.

BIOMARKERS

Wesley Horton, M.S., Foundation for the National Institutes of Health
Pre-Competitive Analytical Validation of SV2A PET as a Biomarker of Synaptic Density Project
$300,000

This three-year project will test a new form of brain scan called SV2A PET imaging that attaches a radioactive substance to the SV2A glycoprotein in brain synapses and then scans to detect changes associated with Alzheimer’s disease. The goal of the next phase of their research is to deepen the biological understanding of SV2A binding within brain synapses and to compare SV2A activity in healthy participants versus people living with mild cognitive impairment and Alzheimer’s disease, and also through brain autopsy in those who have died.

Russell Lebovitz ,M.D., Ph.D., Amprion, Inc.
Misfolded Alpha-Synuclein Aggregates in CSF as Diagnostic and Prognostic Markers for Dementia
$631,600

Dr. Lebovitz and the Amprion team have demonstrated a connection between the detection of misfolded alpha-synuclein proteins in cerebrospinal fluid (CSF) and Lewy Body Dementia, and have demonstrated that the proteins’ early presence in CSF can predict disease progression. The team’s current work focuses on validating a less complex version of the test that can be performed in laboratories that are available to frontline physicians treating patients with dementia. If their validation of the test in a planned study of 400 patients is successful, the test will be submitted to the FDA for approval for commercial use in patients with Lewy Body Dementia.

Rhoda Au, Ph.D., Trustees of Boston University
Alzheimer’s Disease Digital Biomarker Discovery: Framingham Cognitive Aging and Dementia Study
$1,937,857

Dr. Au and her team are collecting data on Alzheimer’s-related characteristics, such as changes in cognition, gait, balance, mood, and depression in a digital format using smart phones and tablets. This data will be collected from subjects participating in the Framingham Study, a long-term, ongoing study that began in 1948 involving thousands of participants in Framingham, Massachusetts. The data will be aggregated and used to create digital profiles that can differentiate between people with stable cognition, cognitive decline, and dementia.

Jennifer Myers, Ph.D., Neurotrack Technologies, Inc.
Digital Multimodal Neuropsychological Phenotyping for the Detection of Cognitive Decline in Aging Adults
$792,990

Dr. Myers and her colleagues at Neurotrack developed a comprehensive digital platform for the assessment of cognitive health in aging populations. Their assessments are designed to be administered on smartphones, tablets, or computers, making them available for use at home or in a doctor’s office. The assessments collect multiple types of data including eye tracking, voice, and touch feedback to measure function in cognitive domains. This project aims to demonstrate the ability of the digital assessment to distinguish between people with normal function, mild cognitive impairment, and Alzheimer’s disease.

Russell Lebovitz, M.D., Ph.D., Amprion, Inc.
Development and Commercialization of a Protein Misfolding Cyclic Amplification (PMCA) Clinical Test for Detection of Aggregates of Misfolded α-Synuclein in Plasma and Plasma Exosomes
$631,653

Dr. Lebovitz and his team aim to validate a highly sensitive and specific blood test for Alzheimer’s disease and other dementias associated with misfolded protein aggregates. Their technology platform detects soluble protein aggregates, identifying what are widely believed to be the critical changes in the brains of people with Alzheimer’s. This offers the opportunity to develop a sensitive diagnostic for Alzheimer’s disease that is suitable for routine clinical screening and able to diagnose the disease prior to the onset of significant cognitive symptoms.

Leyla Anderson, M.D., Ph.D., NeuroVision Imaging, Inc.
Validation of Blood-Based Biomarkers for the Detection of Brain Amyloid Accumulation Before Clinical Onset of Dementia
$539,259

Dr. Anderson and her team have discovered that detection of amyloid and certain metabolites in the blood can provide an early diagnosis of Alzheimer's disease. They are validating the accuracy of this blood test on samples from patients in the Australian Imaging and Biomarker Lifestyle study of aging (AIBL), one of the largest studies of Alzheimer's disease in the world.

Cecilia Lee, M.D., M.S., University of Washington
Identifying an Ophthalmic Combinatorial Biomarker of Early Alzheimer’s Disease Using Novel Imaging and Deep Learning
$498,958

Dr. Lee and her team are using novel, noninvasive imaging tests and deep learning analysis to evaluate multiple eye-related biomarkers and understand how each contributes to an early Alzheimer’s disease diagnosis. By simultaneously evaluating many promising biomarkers in patients who are cognitively normal compared to those who have mild cognitive impairment or early Alzheimer’s disease, they hope to identify a panel of biomarker tests that can be used to diagnose early Alzheimer’s disease and/or predict Alzheimer’s development.

Thomas Montine, M.D., Ph.D., Board of Trustees of the Leland Stanford Junior University
Blood-Based Immune Biomarkers for Alzheimer's Disease Diagnosis and Its Early Detection
$468,500

Dr. Montine and his team have identified novel biomarkers associated with neuroinflammation in blood samples from a cohort of 122 participants. Their current work will validate these blood-based biomarkers in a larger cohort of patients to test if they can be used as predictors of Alzheimer’s disease.