ADDF Awards $15 Million in New Investments Supporting Wide Range of Innovative Alzheimer’s Research

The Alzheimer’s Drug Discovery Foundation (ADDF) announced 15 new investments in the second quarter of 2021 supporting innovative clinical, preclinical and Alzheimer’s biomarker research. The new investments reach into virtually every corner of Alzheimer’s research, including repurposed and novel drug molecules, drug compounds that affect the blood brain barrier, the brain’s energy supply, and specific protein abnormalities that drive pathological changes in Alzheimer’s brains. Biomarker research investments include peripheral biomarkers—minimally invasive eye and blood tests—as well as cutting-edge digital programs.

“The breadth of our investments this quarter demonstrates the ADDF’s willingness to go wherever scientists are doing innovative and promising research,” said Dr. Howard Fillit, ADDF Founding Executive Director and Chief Science Officer. “We continue to seek out and support great scientists working in academia, biotech and technology companies as they develop targeted therapies, repurpose safe drugs that hold promise for Alzheimer’s patients, and seek out digital and peripheral biomarkers to match the many drugs in our robust research pipeline.”

BIOMARKERS

Leyla Anderson, M.D., Ph.D., NeuroVision Imaging
Validation and Commercialization of a Novel Blood-Based, Ultra-Multiplex Laboratory Developed Test for the Prediction of Cerebral Amyloid Status Before Clinical Onset of Dementia
$2,200,950

Dr. Anderson and her team are developing a test to measure several blood biomarkers for the prediction of brain amyloid, a hallmark of Alzheimer’s disease. They plan to use a proprietary nano-sensor that is highly responsive to local magnetic fields, designed by MagArray, in combination with their assays to create an exceptionally robust tool for laboratory diagnostics. They will optimize and validate these assays and submit data from these efforts to the FDA to get certification as a laboratory developed test. This certification will enable physicians to request these blood biomarker tests to help with patient diagnosis.

Zoe Kourtzi, Alzheimer's Research UK
Integration of Multiple Digital Technologies for the Early Detection of Neurodegenerative Diseases
$2,052,000

The Early Detection of Neurodegenerative diseases (EDoN) initiative aims to develop an integrated digital device. As part of the device creation, EDoN intends to evaluate sleep patterns, physical activity levels, smartphone interactions, cognitive function and mood data using wearables and smartphone applications. The integrated device will enable the detection of specific dementia-causing diseases 10-15 years before symptoms become noticeable and can then be used to encourage risk-reducing lifestyle changes, to triage individuals into clinical diagnostic testing, to facilitate research into early stages of disease progression, and to aid the development and testing of therapeutic interventions.

Diana Kerwin, M.D., GAP Innovations, PBC
Development of a Biosample Database to Investigate Beta-Amyloid, Phospho-Tau, and Neurofilament Light Chain Blood-Based and Digital Biomarkers in Older Volunteers Screened for Preclinical Alzheimer’s Disease, Prodromal AD, or Mild AD
$1,500,000

GAP PBC is developing a rigorous “pre-screening” data analytics program that will be deployed in future clinical trials, saving substantial time and tens of millions of dollars in the execution of future trials. To hone its biomarker strategy and optimize AI derived algorithms for trial design and characterizing trial populations, GAP PBC is initiating its own clinical study to organize the first systemic, well-characterized sampling and data collection effort focused on blood-based and digital biomarkers for this purpose.

Nicklas Linz, Ph.D., ki elements
PROSPECT-AD: Population-Based Screening Over Speech for Clinical Trials in Alzheimer’s Disease
$965,827

The aim of this project is to replace in-person manual pre-screening procedures for clinical trials with remote automated methods using a telephone or smartphone with ki elements’ Δelta application, which utilizes cognitive testing and advanced speech-based analytics. The pre-screening process involves the conduct, evaluation, and reporting of neuropsychological testing. This approach will reduce cost and clinical trial screening time for trial participants at the pre-symptomatic stage of Alzheimer’s disease.

Ioannis Tarnanas, Ph.D., Altoida, Inc.
Digitally Enhanced Personalized Medicine: Accurate Selection of Subjective Cognitive Decline and Measuring Progression of MCI
$498,335

Dr. Tarnanas and his team aim to test a novel mobile phone and tablet-based digital biomarker platform that evaluates cognition through a user-friendly exercise that simulates tasks associated with activities of daily living. They propose to show the usefulness of this platform for detecting individuals at high risk for Alzheimer’s disease, namely in subjective cognitive decline (SCD) and mild cognitive impairment (MCI) subjects, allowing them to track disease progression in these patients.

David Salzman, Ph.D., Gatehouse Bio, Inc.
Multi-Class Classifier for CNS Disorder Type and Alzheimer’s Disease Progression
$349,000

Gatehouse Bio is creating “classifiers” for Alzheimer’s disease and related comorbidities. Their work uses an AI-powered, computational platform to analyze small RNA sequencing data from cerebrospinal fluid to identify patterns that can be assessed as biomarkers to measure existing disease or predict future disease. Once validated, these classifiers will be helpful in selecting patients for clinical trials and can add vital information to publicly available data sets that researchers are using to study neurodegenerative diseases.

Christie Sheehy, Ph.D., C. Light Technologies, Inc.
Fixational Eye Motion as Biomarker for Mild Cognitive Impairment
$251,021

Dr. Sheehy and her team aim to use a device developed by C. Light Technologies called the tracking scanning laser ophthalmoscope (TSLO) device to record involuntary eye movements in patients with mild cognitive impairment (MCI) and use these movements as a biomarker for the disease. The tracking of these eye motions will provide granular disease progression mapping/feedback, with the end goal of early detection for MCI. The team will be working in collaboration with the Memory and Aging Center at the University of California, San Francisco.

Wesley Horton, M.S., Foundation for the National Institutes of Health
Neurofilament as a Fluid Biomarker of Neurodegeneration in Familial Frontotemporal Degeneration (f-FTD)
$250,000

In a consortium of pharmaceutical companies and academic institutions, the team led by Mr. Horton at the FNIH aims to evaluate several methods to measure blood Neurofilament (Nf). Nf is a protein polymer that provides structural support for nerve fibers and becomes elevated with the onset of neurodegeneration. The goal is to determine whether the methods are sufficiently robust and reproducible to be utilized as a biomarker for increased risk of conversion to symptomatic disease in individuals with familial frontotemporal degeneration (f-FTD) mutations.

Martin Zhang, M.D., Ph.D., Massachusetts General Hospital
Molecular Neuroimaging of RIPK1/Necroptosis in Alzheimer’s Disease
$206,836

Dr. Zhang and his colleagues are developing a novel positron emission tomography (PET) imaging test to measure levels of the RIPK1 protein. High levels of the protein are implicated in formulation of amyloid plaques and inflammatory changes in the brains of people with Alzheimer’s, making RIPK1 an important therapeutic target for both understanding and treatment of the disease.

CLINICAL

Clive Ballard, M.B. Ch.B., University of Exeter
A Placebo Controlled, Randomized Double-Blind Parallel Group 12-Month Trial of Fasudil for the Treatment of MCI due to Alzheimer’s Disease, Nested within a Multi-Arm Phase 2 Clinical Trial Platform
$3,024,684

Dr. Ballard and his team will run a 12-month clinical trial comparing treatment with fasudil to a placebo treatment in 200 people with early Alzheimer’s disease. They will measure safety and the potential benefits of the drug using sensitive computerized tests of cognitive function, imaging and fluid biomarker analyses. An international expert panel was recently convened to determine the best emerging repurposing drug candidates, and fasudil was identified as the most promising for Alzheimer’s. In vitro and in vivo studies in Alzheimer’s models have shown fasudil to have promising protective effects, and improve the memory of treated mice.

David Livingston, Ph.D., Metro International Biotech
MIB-626 for Treatment of Mild Dementia Patients
$3,000,000

Metro International Biotech is developing a compound called MIB-626 for the treatment of patients with Alzheimer’s disease. MIB-626 has many properties that could help reduce inflammation and other mechanisms underlying Alzheimer’s, but there are questions about how effectively it can cross the blood-brain barrier. This project will include two randomized control clinical trials of MIB-626 in patients with mild dementia. The objective of the first trial is to determine whether MIB-626, after daily oral administration for 90 days, penetrates the blood brain barrier. If the primary outcome is met in the first trial, a second trial will be planned to determine whether MIB-626 dosed orally for 180 days improves indicators of disease, including amyloid biomarkers in cerebrospinal fluid, synaptic function and neuroinflammation. The compound will also be assessed for improvement of cognition and activities of daily living in the trial participants.

PRECLINICAL

Wen-Hsuan Chang, Ph.D., AcuraStem
Development of PIKFYVE Antisense Oligonucleotides (ASO) Treatment
$165,000

AcuraStem is developing a compound to suppress a protein in the brain called PIKFYVE. Suppressing PIKFYVE prevents degeneration of patient neurons in the laboratory and has been shown to prevent loss of motor function in mice. Importantly, the compound has not caused toxicity in the human motor neurons nor in animal models. Dr. Chang and colleagues at AcuraStem are further validating the efficacy and safety of their drug to determine whether to proceed to studies in humans.

Anna Orr, Ph.D., Weill Cornell Medicine
Lead Optimization of Novel Site-Selective Blockers of Mitochondrial Complex III ROS as FTD Therapeutics
$135,000

Mitochondria produce energy essential for cells, but they also release damaging free radicals that may contribute to frontotemporal degeneration (FTD) and related dementias. Dr. Orr and her colleagues are working on a new class of compounds that hold promise for reducing neurodegeneration and brain inflammation linked to these free radicals. Their current studies are expected to identify novel molecules for potentially treating FTD and related disorders of the brain.