NEW YORK, May 10, 2016 /PRNewswire-USNewswire/ -- The Alzheimer's Drug Discovery Foundation (ADDF) has awarded 10 new grants to researchers developing drugs for neurodegenerative diseases and biomarkers to detect their onset and progression. The grants include funding for four novel programs with the potential to treat a range of diseases, including Alzheimer's, Huntington's, and Parkinson's.
Dr. Howard Fillit, Founding Executive Director and Chief Science Officer of the ADDF, says: "These investments illustrate our commitment to pioneering ideas for treating Alzheimer's and other causes of dementias. Our funding for biomarkers has already revolutionized diagnosis and clinical trials in the field and we are advancing four promising programs to measure proteins, microRNA and enzymes involved in Alzheimer's disease."
Edward Huey, MD, Columbia University
Low-Dose Lithium for the Treatment of Behavioral Symptoms in Frontotemporal Dementia
Agitation, aggression, and repetitive behaviors are common symptoms of frontotemporal dementia (FTD). These symptoms are difficult to treat and distressing to patients and caregivers, often lead to institutionalization. Antipsychotic medications are frequently prescribed, but often cause side effects including Parkinsonism and increased mortality. Dr. Huey will test the use of low-dose lithium for the treatment of behavioral symptoms in FTD patients. Lithium is a highly effective treatment for agitation in mania. And preliminary data in Alzheimer's disease shows that patients with no or partial response to other medications had decreased agitation and aggression with lithium treatment.
This grant is funded through the ADDF's partnership program with the Association for Frontotemporal Degeneration (AFTD).
Travis Dunckley, PhD, Translational Genomics Research Institute
Testing Selective DYRKIA Inhibitors as a Novel Treatment for Alzheimer's Disease
The accumulation of tau protein into tangles is associated with neurodegeneration and cognitive decline in Alzheimer's disease. These toxic tangles form when tau is abnormally phosphorylated (or tagged) by enzymes known as kinases. New treatments that target overactive kinase activity and abnormal phosphorylation of tau and other proteins could slow the progression of Alzheimer's. Dr. Dunckley and his colleagues have developed two novel compounds to inhibit DYRK1A, a kinase that phosphorylates tau, as well as amyloid precursor protein (APP) and presenilin 1. Preliminary data indicates that DYRK1A inhibitors safely reduce phosphorylated tau levels in the brain. The goal of these preclinical tests is to assess whether DYRK1A inhibitors delay cognitive decline and the onset of Alzheimer's. If successful, the proposed studies will provide critical data to advance one of these drug candidates toward clinical trials.
Pontus Forsell, PhD, AlzeCure Foundation
NeuroRestore, Developing Positive Allosteric Modulators of TrkA and TrkB
A large body of evidence suggests that certain growth factors are involved in the health and proper functioning of nerve cells. Dr. Forsell and his team at AlzeCure have identified small molecules that boost the effects of these growth factors. They used those molecules to develop several compounds and have already improved their potency by more than 20-fold. With this grant, they will continue to develop these lead chemical compounds. Once optimized, they could have neurorestorative as well as cognitive boosting effects in patients with Alzheimer's disease.
Thota Ganesh, PhD, Emory University
EP2 Antagonists for the Suppression of Inflammation and Neuropathology in Alzheimer's Disease
Studies have found that the prostanoid EP2 receptor promotes inflammation and other hallmarks of Alzheimer's disease. Therefore, developing drugs to block the EP2 receptor may halt disease progression. Dr. Ganesh developed novel compounds that block the activity of this receptor. Dr. Ganesh and his team were able to improve these compounds with support from experienced industry consultants made available through the ADDF's partnership with the Harrington Discovery Institute. This add-on funding will continue Dr. Ganesh's access to experts from Harrington as he completes preclinical testing of his drug candidates.
Stephen Salton, MD, PhD, Icahn Institute for Genomics and Multiscale Biology at Mount Sinai
VGF Peptide Delivery for the Suppression of Memory Impairment in Alzheimer's Disease
VGF, a neuropeptide found in the brain, may help protect against brain injury, foster healthy energy balance, and promote memory formation. Patients with Alzheimer's disease and amyotrophic lateral sclerosis (ALS) have decreased levels of this peptide in their brains. This study will test whether treatment with VGF-related peptides has beneficial effects on a mouse model of Alzheimer's disease. If successful, Dr. Salton and his colleagues will develop a drug to mimic these effects of VGF or to safely deliver VGF to human brains.
Brent Stockwell, PhD, Columbia University
Protein Disulfide Isomerase (PDI) Inhibitors as Neuroprotective Agents for Alzheimer's Disease
Misfolded proteins such as tau and amyloid can aggregate into tangles and plaques that damage neurons and ultimately cause them to die, which contributes to the development of Alzheimer's disease. Previous research has found that protein disulfide isomerase (PDI)—a molecular "chaperone" that ensures proper folding—becomes dysfunctional in those with Alzheimer's and several other diseases. With a previous grant from the ADDF, Dr. Stockwell and his colleagues discovered a compound that modulates PDI and protects neurons from the toxic effects of misfolded tau protein. They now plan to develop a therapeutic drug that targets abnormal tau protein misfolding and has the potential to prevent or delay tau-associated damage in the brains of Alzheimer's patients. This approach may have applications for other neurological protein misfolding diseases, such as Parkinson's and Huntington's.
The following grants support the development of tools to advance our understanding of Alzheimer's disease by tracking its progression, improving patient selection for clinical trials, and monitoring patient response to drugs in trials.
Jacob Hooker, PhD, Massachusetts General Hospital
Epigenetic Mechanisms in Human Memory: Quantification by PET Imaging in the Aged Brain
Epigenetics, a process that influences how our genes are expressed, is an emerging area for Alzheimer's therapies. Current imaging agents that measure aspects of Alzheimer's disease are valuable but limited to "downstream" protein aggregates such as amyloid rather than epigenetic changes that happen much earlier. Dr. Hooker and his team have developed the first and only imaging agent targeting class-I histone deacetylases (HDAC), which are enzymes involved in epigenetic changes. They have advanced the imaging agent to first-in-human clinical trials and are now planning studies in healthy seniors and those with Alzheimer's (75-90 years old). They hope to determine whether class-I HDAC expression is altered in aging brains and in those with Alzheimer's and whether it can serve as an early imaging biomarker of Alzheimer's. The outcomes of this study will provide an important tool for novel drug trials.
Gerard Nuovo, MD, Gnome Diagnostics, LLC.
The Utility of cFLIP and MCL1 and Their Regulatory MicroRNAs as Novel Biomarkers of Alzheimer's Disease
Several well-validated cerebrospinal fluid (CSF) biomarkers have been developed for Alzheimer's disease. Adding new biomarkers to the existing cadre will reduce false-positives and improve early detection and the selection of patients for clinical trials. MicroRNAs, which are regulatory molecules that control expression of certain proteins, have recently emerged as viable biomarker candidates for Alzheimer's. Dr. Nuovo and his colleagues have found that specific microRNAs were markedly reduced—while cFLIP and MCL1, two known target proteins were elevated—in late-stage Alzheimer's disease. In this project, Dr. Nuovo seeks to validate his findings in samples from early-stage Alzheimer's patients and further develop these novel CSF biomarkers for Alzheimer's.
Neil Vasdev, PhD, Massachusetts General Hospital
Translation of an Optimized PET Radiopharmaceutical for Imaging Tau Pathology in Alzheimer's Patients
The invention of imaging agents used in positron emission tomography (PET) to detect amyloid plaques (such as the ADDF-funded Amyvid™ test) led to major breakthroughs in clinical dementia research and drug development. In such studies, radioactive drug molecules (radiopharmaceuticals) are injected and the distributions of those molecules are measured using a PET camera. A similar imaging agent for tau proteins, thought to play an important role in early Alzheimer's disease, could lead to more breakthroughs by allowing researchers to rapidly identify novel Alzheimer's drug treatments that engage and modify the tau proteins in the brain. Dr. Vasdev and collaborators from Merck will develop and evaluate a new tau imaging agent in clinical tests.
Peter Working, PhD, Alzeca Biosciences
Novel MRI Contrast Agent for Detection of Beta Amyloid
The build-up of amyloid plaques in the brain is a hallmark of Alzheimer's disease. The invention of positron emission tomography (PET) agents (including the ADDF-supported Amyvid™ test) that image and quantitatively measure amyloid plaques has revolutionized Alzheimer's diagnosis, clinical trials, and prevention studies. However, PET imaging requires radioactivity and is expensive and time-consuming to conduct. Dr. Working and the team at Alzeca Biosciences are developing a proprietary agent to visualize amyloid plaques using magnetic resonance imaging (MRI). This has the potential to provide a more widely available, non-radioactive, low-cost alternative to traditional PET agents, while providing higher resolution.
Alzheimer's Drug Discovery Foundation
Founded in 1998 by Leonard A. and Ronald S. Lauder, the Alzheimer's Drug Discovery Foundation (ADDF) is dedicated to rapidly accelerating the discovery of drugs to prevent, treat and cure Alzheimer's disease. The ADDF is the only public charity solely focused on funding the development of drugs for Alzheimer's, employing a venture philanthropy model to support research in academia and the biotech industry. Through the generosity of its donors, the ADDF has awarded nearly $90 million to fund more than 500 Alzheimer's drug discovery programs and clinical trials in 18 countries. To learn more, please visit: http://www.alzdiscovery.org/.
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SOURCE Alzheimer's Drug Discovery Foundation