ADDF Awards Nearly $18 Million in New Investments Supporting Cutting-Edge Alzheimer’s Prevention, Treatment and Biomarker Research

The Alzheimer’s Drug Discovery Foundation (ADDF) recently announced 13 new investments supporting innovative research focused on diverse strategies for preventing, treating and diagnosing Alzheimer’s disease and related dementias. Among the awards is a $3 million dollar investment in the FINGER 2.0 study, the first global study for preventing dementia and Alzheimer’s disease.

The study, under the leadership of Dr. Miia Kivipelto, is combining lifestyle interventions, which were shown in the first FINGER study to prevent cognitive decline — such as diet, exercise and management of vascular and metabolic risk factors — with a repurposed diabetes drug, metformin. By helping the body use insulin more effectively, metformin may prevent metabolic changes in the brain that often come with aging and that are associated with cognitive decline.

“Prevention is vital in the fight against Alzheimer’s disease because delaying onset by even a few years can make a great difference in people’s lives,” said Dr. Howard Fillit, Co-Founder and Chief Science Officer of the ADDF. “This is why the ADDF supports programs to attack Alzheimer’s from all sides, supporting prevention, treatment, and early diagnosis research that gives us the best chance of stopping this disease.”

PREVENTION

Miia Kivipelto, M.D., Ph.D., Imperial College London
MET-FINGER-APOE: A randomized controlled trial of multimodal lifestyle intervention and metformin to prevent cognitive impairment and disability in a cognitively healthy APOE4 enriched at-risk population
$2,999,865

The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) is the only intervention trial that has demonstrated significant cognitive benefits from lifestyle interventions in at-risk individuals. Researchers are now evolving the model by combining lifestyle improvements with disease-modifying drugs in FINGER 2.0, which adds the widely used diabetes drug metformin. The worldwide trial will include individuals from the U.K., Sweden and Finland. This project, which is being led by ADDF board member Miia Kivipelto and a team of international experts in Alzheimer’s disease and type 2 diabetes, will provide crucial knowledge about Alzheimer’s prevention.

Dean Ornish, M.D., Preventive Medicine Research Institute
Can lifestyle changes stop or reverse the progression of MCI due to early-stage Alzheimer's disease?
$2,500,000

This is the first randomized controlled trial to evaluate whether early-stage Alzheimer’s disease and mild cognitive impairment progression can be stopped or reversed by comprehensive, intensive lifestyle interventions. The interventions include a whole foods plant-based diet low in fat and refined carbohydrates with selected supplements, moderate exercise, stress management, and support groups.

DRUG DISCOVERY AND DEVELOPMENT

Paul Edison, M.D., Ph.D., Imperial College London
Evaluating the effects of GLP-1 analog, oral semaglutide, as a treatment for sporadic behavioral variant frontotemporal dementia
$2,000,000

Dr. Edison’s multi-center study is evaluating the effect of oral semaglutide in the behavioral variant of frontotemporal dementia (bvFTD), which is characterized by prominent changes in social behavior and personality caused by degeneration of the front part of the brain. Oral semaglutide is a tablet approved for the treatment of diabetes. The aim of the study is to evaluate whether semaglutide could be used as a treatment for bvFTD by assessing the influence of the drug on brain volume, memory and understanding, and blood biomarkers in FTD patients.

Simon Ducharme, M.D., McGill University
Open-label clinical trial of nabilone for neuropsychiatric symptoms in frontotemporal dementia
$1,399,077

The trial is testing whether the repurposed generic drug nabilone, a synthetic cannabinoid that has been shown to have benefits in treating agitation in Alzheimer’s disease, also has beneficial properties in reducing brain inflammation in patients with frontotemporal dementia. This will be the first open-label clinical trial of nabilone for agitation in FTD and will obtain data on effectiveness, optimal dose and tolerability.

Philip Scheltens, M.D., Ph.D., Vrije Universiteit Amsterdam
Testing low-dose efavirenz treatment for Alzheimer’s disease: A phase 1b dosing, target-engagement and exploratory biomarker study
$855,541

Research suggests that modulating brain cholesterol and its derivatives might be a beneficial therapeutic approach for treating Alzheimer’s disease. In the laboratory, efavirenz, a repurposed drug approved for AIDS treatment, significantly altered several biochemical changes that have an effect on cholesterol levels in the brains of people with Alzheimer’s. This phase 1 study will test the safety of efavirenz in patients with early Alzheimer’s disease and provide preliminary data in its effect on brain cholesterol turnover and other biomarkers of the disease.

Jennifer Cermak, Ph.D., Life Biosciences
Effects of chaperone-mediated autophagy in Alzheimer's disease
$630,460

Chaperone-mediated autophagy (CMA) is the biological process responsible for breaking down and clearing old and damaged proteins in the body. Aging and certain diseases like Alzheimer's appear to cause dysfunction in this process, allowing damaged proteins to clump and accumulate in the brain. A new class of drugs is being developed to reactivate this recycling process in an effort to clear this “cellular garbage” and keep neurons healthy and functioning to protect memory

BIOMARKERS

Jean-Philippe Sylvestre, Ph.D., Optina
Validation of the Retinal Deep Phenotyping™ Platform for the detection of the likely cerebral amyloid status to aid in the diagnosis of Alzheimer’s disease
$2,135,000

Dr. Sylvestre and his team aim to validate the ability of Optina’s proprietary platform to detect the brain’s amyloid status by imaging of the retina, the only optically accessible part of the central nervous system. The goal is to eventually replace expensive amyloid PET scanning with a more accessible and easier-to-administer retinal scan that can accurately detect this key hallmark of Alzheimer’s disease.

Frank Menniti, Ph.D., MindImmune
Measurement of immune cell recruitment as a biomarker of neuroinflammation in Alzheimer's disease and other diseases of the central nervous system
$1,835,000

MindImmune is developing a new therapeutic approach to block certain immune cells from crossing from the blood into the brain, where they attack the brain’s synapses, damaging the means through which the brain’s synapses communicate. The ADDF’s investment supports development of a contrast agent, which acts as a kind of dye that is injected into the blood to help with imaging, allowing researchers to "see" immune cell infiltration into the brain. This may serve as a new diagnostic for the disease and as an aid to the development of MindImmune's new therapeutic approach.

Manu Vandijck, M.Sc., Fujirebio
Easy and early plasma pTau181 detection with the LUMIPULSE G platform as indicator of Alzheimer's disease
$1,442,198

Dr. Vandijck and his team are developing and validating a blood test to assess levels of brain pTau181 in a neurologically diverse population. Commercialization of an easy-to-run and fully automated blood test will help with simple and rapid identification of individuals with Alzheimer’s disease, facilitating more efficient drug trial enrollment. It may also assist in diagnosis of the millions of individuals suffering from dementia.

Matthew Pase, Ph.D., Monash University
Plasma neuroinflammatory biomarkers for the diagnosis of dementia subtypes
$671,160

The team at Monash University will evaluate whether their blood test measuring neuroinflammation biomarkers can differentiate among the most common types of dementia (e.g., Alzheimer’s, frontotemporal dementia) in an ethnically diverse group of 600 patients with newly diagnosed dementia. This work will add to the growing knowledge about the biology of neuroinflammation in different dementias and pave the way for minimally invasive diagnostic tools that can aid with diagnosis.

Qinwen Mao, M.D., Ph.D., University of Utah
Plasma pathologic TDP-43 as a biomarker for FTLD-TDP
$500,000

This study is aiming to develop a blood test that can measure pathologic levels of certain forms of TDP-43, a binding protein that commonly accumulates in the brains of people with various neurodegenerative diseases. The study will assess the ability of a sensitive and specific TDP-43 biomarker to distinguish between different forms of frontotemporal degeneration, Alzheimer’s disease and normal aging.

Rafael Polania, Ph.D., ETH Zurich
Towards an integral and sensitive neurophysiological risk biomarkers for asymptomatic detection of Alzheimer’s disease
$470,007

ETH Zurich has developed portable technology (EAR-DREAM) that provides long-term, non-obtrusive recordings of brain signals from the ear. In this study, EAR-DRUM will record these signals in the largest known population of patients who carry the autosomal dominant Alzheimer’s mutation (ADAD), which carries a 100% chance of developing Alzheimer’s, and compare them to recordings from a control group that does not carry the ADAD mutation. Investigators will develop, via state-of-the-art predictive models, a robust biomarker of Alzheimer’s risk from the data collected.

Ramit Ravona-Springer, M.D., Medical Research Development and Health Services Fund by the Sheba Medical Center
Novel virtual reality method to distinguish apathy from depression in the context of dementia
$94,097 in add-on funding

This additional funding will continue to support Dr. Ravona-Springer’s work to develop a novel virtual reality tool that can objectively measure apathy, which affects four in five Alzheimer’s patients. Apathy is often misdiagnosed as depression, leading to unnecessary and incorrect drug intervention, as well as increased caregiver burden. By improving diagnosis of apathy, this virtual reality tool can advance clinical trials focused on developing appropriate treatments by providing an objective measure for patient trial enrollment and ongoing measurement of treatment effect.