$4.2 Million in New Funding from ADDF Advances Diverse Research for Alzheimer’s and FTD

The Alzheimer’s Drug Discovery Foundation (ADDF) announces six new investments, totaling more than $4.2 million, to help advance clinical, pre-clinical and biomarker research programs focused on novel therapeutic targets and innovative approaches for the treatment and prevention of Alzheimer’s disease and related dementias. The new funding includes three investments in partnership with the Association for Frontotemporal Degeneration (AFTD) focused on frontotemporal dementia (FTD), a rare type of dementia that most often strikes adults in the prime of life, typically in their 40s and 50s.

“Today’s awards truly demonstrate the breadth and depth of the ADDF’s research interests and the range of exciting dementia research happening today,” said the ADDF’s Founding Executive Director and Chief Science Officer Dr. Howard Fillit. “The new funding highlights our long history of collaboration with AFTD. Such partnerships play a key role in the fight against Alzheimer’s and related dementias.”

Two awards are part of the Treat FTD Fund, a 10-year, $10 million dollar fund to support clinical trials for FTD. Funding also supports the development of novel, preclinical drugs through the ADDF’s Accelerating Drug Discovery for Frontotemporal Degeneration partnership and through the ADDF-Harrington Scholar Program. The additional awards support the development of PET and MRI scans, which provide ways to identify the right patients for clinical trials with specific drugs and monitor treatment effects.

CLINICAL

Emiliano Santarnecchi, PhD, Harvard Medical School/Beth Israel Deaconess Medical Center
Non-Invasive Brain Stimulation for Gamma Induction and Cognitive Enhancement in FTD
$1,959,841

Recent work has shown that non-invasive brain stimulation can modulate brain activity and may even be able to influence disease pathology in people with FTD. This clinical trial, supported as a part of the Treat FTD Fund, will test whether noninvasive brain stimulation can alleviate symptoms and change brain activity in FTD patients. If successful, the study will establish the safety and tolerability of such an approach, gather critical insights into the mechanisms behind the disease, and lay the foundation for future use by the patient in their own home.

Giacomo Koch, MD, PhD, Santa Lucia Foundation
Dopaminergic Therapy for Frontotemporal Dementia Patients
$602,800

Recently, it has been hypothesized that impairment in the dopaminergic system, which regulates the movement and degradation of dopamine (a chemical in the brain involved in reward-seeking behaviors) could be implicated in one type of FTD called behavioral variant FTD, or bv-FTD for short. Drugs that affect dopamine have been shown in Dr. Koch’s earlier ADDF funded research to improve executive functions in mild Alzheimer’s patients. Dr. Koch will test the safety and efficacy of rotigotine to see whether the drug also affects debilitating symptoms that may relate to dopamine in bv-FTD patients. This work, funded in partnership with the AFTD, will deepen our understanding of the role of dopamine dysfunction in patients with bv-FTD as we search for an effective treatment.

DRUG DISCOVERY

John “Kent” Werner, MD, PhD, Cogentis Therapeutics
Preclinical Pharmacokinetics and Pharmacodynamics of CT-526 in the Tauopathy Mouse Model
$188,193

In a healthy brain, the enzyme CDK5 is normally active, but during stressed conditions (such as aging), CDK5 can become hyperactive. This hyperactivity can disrupt normal brain signaling and contribute to the toxic clumping of tau, which has been identified as a major contributor to the abnormal brain pathology seen in patients with frontotemporal dementia (FTD). Cogentis Therapeutics has a novel drug called CT526 that can prevent abnormal hyperactivity of CDK5. In a mouse model of Alzheimer’s disease, treatment with CT526 reversed memory loss, as well as other brain deficits, and significantly extended lifespan with no detectable toxic side effects. This project is a part of the ADDF’s joint program with the AFTD on Accelerating Drug Discovery for FTD and will further examine CT526 to determine the appropriate dose range for studies in humans.

Eugenia Trushina, PhD, Mayo Clinic Rochester
Development of Small Molecules Modulators of Mitochondrial Function
$600,000

Dr. Trushina, as the 2019 recipient of the ADDF-Harrington Scholar Award, has received funding, as well as in-depth advisory support from pharmaceutical industry experts on the Harrington team, to develop drug compounds that target metabolic dysfunction in neurons. This is one of the earliest changes seen in the brains of people with Alzheimer’s, even appearing before amyloid plaques, tau tangles and cognitive symptoms become evident. The compounds Dr. Trushina and her team have tested have shown a positive effect in both symptomatic and pre-symptomatic models of the disease.

BIOMARKERS

Martin Pomper, MD, PhD, Precision Molecular Inc.
Targeting Macrophage CSF1R as a PET Imaging Biomarker for Alzheimer’s Disease
$561,111

Inflammation has become a widely recognized component of Alzheimer’s disease, but the available tools to sensitively measure it in the brains of living patients are limited. Dr. Pomper is developing a novel imaging agent that will help to see early changes in microglia, which are the immune cells of the brain that are thought to partially underlie the inflammatory component of Alzheimer’s disease. His team will visualize and measure the degree of microglia cell activation in the brains of patients with Alzheimer’s compared to healthy, age-matched, cognitively normal people. Validating this imaging approach will allow researchers to better understand inflammation in Alzheimer’s disease and identify the right patients for clinical trials of anti-inflammatory drugs.

Chunlei Liu, PhD, University of California, Berkeley
Validating Magnetic Susceptibility as a Biomarker for Iron-related Oxidative Stress and White Matter Changes in Alzheimer’s Disease
$300,000

In Alzheimer’s disease, molecules damaged by free radicals can build up and cause toxic damage in the brain. Currently, there are no established ways to measure this process in living patients. Therefore, identifying and developing methods to measure other aspects of the disease are needed. This project will fill this gap by further developing a novel MRI technique to image features of oxidative stress, which causes extensive damage to fats, proteins and DNA in the brains of Alzheimer’s patients. Validating this imaging approach will allow researchers to measure damaging molecules in living human brains and help identify patients for clinical trials of anti-oxidant therapies.