$5.8 Million in New Funding Furthers Diverse Pipeline of Novel Approaches

The Alzheimer’s Drug Discovery Foundation (ADDF) announced seven new investments, totaling more than $5.8 million. These new awards are advancing promising approaches to diagnosing, treating and preventing Alzheimer’s disease and related dementias.

This funding supports three clinical trials, including one that explores the use of gene therapy to lower the risk of Alzheimer’s disease, and another that is testing a repurposed drug originally developed to treat sickle cell anemia as potential treatment for early and mild stages of Alzheimer’s. Funding also includes support of a prevention program investigating the potential use of intranasal insulin to prevent or treat postoperative delirium or cognitive dysfunction.

Additionally, four investments, as part of the ADDF’s Diagnostics Accelerator, focus on accelerating the discovery of innovative biomarkers and diagnostic technologies that will aid in Alzheimer’s diagnosis and clinical trial design. 

CLINICAL

Ronald Crystal, MD, LEXEO Therapeutics
Phase I Clinical Trial for the AAV Mediated Treatment of APOE4 Homozygous Alzheimer’s Disease
$1,977,336

The ADDF began funding Dr. Crystal and his gene therapy project at Weill Cornell Medical College in 2004.  A pioneer in the gene therapy field, he applies his expertise to Alzheimer’s through his work with the APOE gene. Inheriting the APOE4 variant of the gene conveys a higher risk for the disease, while inheriting the APOE2 variant appears to lower Alzheimer’s risk. Dr. Crystal’s group has generated impressive preclinical data in animals delivering APOE2 to the brain using an injection method. In his current phase 1 clinical trial, Dr. Crystal is testing the safety and preliminary efficacy of the APOE2 gene therapy in people with two copies of the APOE4 gene who have mild cognitive decline or early dementia. With his new company, LEXEO Therapeutics, Dr. Crystal and his team seek to expand the phase I clinical trial and enable the team to move the program into phase 2 trials.

John Olichney, MD, University of California at Davis
A Phase 2 Repurposing Trial of Senicapoc for Prodromal and Mild Alzheimer’s Disease
$600,000

Dr. Olichney and his team plan to test Senicapoc, a drug that was originally developed for sickle cell anemia, in a phase 2 pilot study in Alzheimer’s patients in the prodromal (early) and mild disease stages. An interdisciplinary team of researchers at UC Davis identified a potassium activated calcium channel that modulates microglial activity as a novel anti-inflammatory target for Alzheimer’s disease and senicapoc blocks this ion channel. The ADDF previously provided funding to manufacture the drug for this clinical trial, which is being supported by the Alzheimer’s Association and is set to start early this year. The ADDF is now providing add-on funding that will enable the team to expand the trial with additional patients. It will also add a brain imaging sub-study to help gain more insight into the drug’s effectiveness.

PREVENTION

Dimitrios Kapogiannis, MD, National Institute on Aging
Does Intranasal Insulin Administration Preserve Cognitive Function after Cardiac Surgery?
$336,432

Brain function may decline after surgery and older patients undergoing open heart surgery are especially at risk. Surgeries can trigger inflammation, which in turn can contribute to impaired insulin signaling in the brain, leading to cognitive dysfunction. Currently, there are no medications available that prevent or treat postoperative delirium or postoperative cognitive dysfunction.

Dr. Kapogiannis will carry out the biomarker arm of a clinical trial supported by the ADDF which is testing whether intranasal insulin preserves cognitive function and decreases risk of postoperative delirium and postoperative cognitive dysfunction. The intranasal route has the benefit of delivering insulin directly into the brain to decrease brain insulin resistance and brain inflammation. Intranasal delivery of insulin does not affect insulin levels in the blood, and therefore does not cause hypoglycemia. Dr. Kapogiannis and his team will isolate vesicles of neuronal origin from the patients’ blood to evaluate the treatment’s effect on insulin resistance in the brain.

BIOMARKERS

Marta Barrachina, PhD, MBA, ADmit Therapeutics S.L.
ADmit Test: A New Kit for Early Alzheimer’s Disease Detection
$497,652

ADmit Therapeutics has developed a way to measure the dysfunction inside cells by examining modifications to mitochondrial DNA, which can be associated with various disorders including neurodegenerative diseases. The team has found that specific modifications of this DNA are predictive of progression to Alzheimer’s disease and may represent an early indicator of the disease. Development of a blood test to evaluate these DNA modifications could potentially enable better selection of patients for clinical trials and further understanding of the disease.

Raj Krishnan, PhD, Biological Dynamics, Inc
Novel Platform for On-Chip Detection of Neuronal Extracellular Vesicles Biomarkers for Alzheimer’s Disease in Plasma
$1,836,770

Dr. Krishnan and his colleagues at Biological Dynamics have developed the Verita™ system, which enables the automated capture and analysis of proteins on the surface of exosomes. Exosomes are small bubbles released from cells (including neurons) that contain many types of biomarkers, including those that reflect pathological changes in the brain which indicate Alzheimer’s disease. Detecting several exosome-based biomarkers has the potential to improve detection and diagnosis of Alzheimer’s, as well as enhancing drug discovery applications.

Gregory Penner, PhD, NeoNeuro
Blood Diagnostic Test for Alzheimer’s Disease: Aptamer Deep Biomarker Fingerprinting
$363,000

NeoNeuro has developed a potentially revolutionary approach to diagnostics using aptamers. Aptamers are small synthetic DNA sequences that bind to targets in blood which are diagnostic of various stages of Alzheimer’s disease. These aptamers can be rapidly and cost-effectively used on individual blood samples with the technological platforms (called polymerase chain reaction, PCR) already available in testing laboratories. The blood test could potentially identify individuals with high levels of amyloid (a key risk factor for the onset of Alzheimer’s disease) and aid in pre-screening of potential enrollees for clinical trials.

Ramit Ravona-Springer, MD, Sheba Medical Center
Novel Virtual Reality Method to Distinguish Apathy from Depression in the Context of Dementia
$249,810

Dr. Ravona-Springer and her team are developing a novel virtual reality tool that will objectively measure apathy. Apathy impacts many patients with Alzheimer’s disease and is often misdiagnosed as depression, leading to unnecessary and incorrect therapeutic intervention as well as increased caregiver burden. This virtual reality tool has the potential to advance clinical trials focused on developing effective therapies for apathy caused by dementia by providing objective measures for patient selection.