FOR IMMEDIATE RELEASE
Contact: Steve Schmidt, 619-206-9108
GROUNDBREAKING GRANTS OPEN NEW AVENUES OF ALZHEIMER’S RESEARCH
SAN DIEGO, CA, OCTOBER 28, 2015 – Regional leaders and top researchers today stepped up their efforts to end Alzheimer’s disease, naming the first recipients of an innovative fund aimed at finding a treatment or cure.
Eight world-class researchers have been selected by Collaboration4Cure, a local grant program established last year, to pursue promising drug discovery projects. They will be given direct access to state-of-the-art equipment, resources and expertise at Sanford Burnham Prebys Medical Discovery Institute and The Scripps Research Institute.
The grant recipients were named at a press event in La Jolla that included Mayor Kevin Faulconer, San Diego philanthropist Darlene Shiley, county Supervisor Dianne Jacob and Mary Ball, president and CEO of the Alzheimer’s Association San Diego.
The goal of Collaboration4Cure is tap into the region’s best minds and resources to increase the success of finding chemical compounds that can attract further external funding and foster the development of a pipeline of possible therapeutic drugs for Alzheimer’s disease.
“Sanford Burnham Prebys Medical Discovery Institute is proud to be part of C4C,” said Michael Jackson, MD. “San Diego is home to some of the best neuroscientists in the world, and with our advanced screening and drug discovery capabilities at the Conrad Prebys Center for Chemical Genomics, we hope to quickly advance research to prevent, treat, and even cure this terrible disease.”
The eight researchers are based at UCSD and SBP and were carefully screened by a C4C committee made up of researchers from UCSD, The Venter Institute, SBP, The Scripps Research Institute, The Salk Institute and external panelists selected by the Alzheimer’s Association.
San Diego is an epicenter for Alzheimer’s research, putting it in the perfect position to execute a cooperative approach to narrowing the “Translational Gap” that currently is preventing the progress of Alzheimer’s drug discovery. In simple terms, these projects will help to bridge the gap between academic research and drug development and in doing so, accelerate our hope for discovering new drugs to treat and prevent Alzheimer’s disease.
“Day in and day out, our research institutes are providing new opportunities to San Diego through new projects, jobs and world-changing ideas,” said Mayor Faulconer. “Collaboration4Cure is on its way to becoming another world-changing project that combines San Diego’s know-how, collaboration and innovation to provide global breakthroughs for Alzheimer’s. Thanks to Darlene Shiley and the Alzheimer’s Association San Diego, our city is engaged as a global leader in the search for a cure that ails so many of our elderly loved ones.”
Alzheimer’s disease is reaching epidemic proportions across our nation and in San Diego. It is San Diego’s third leading cause of death and, as our rapidly aging population grows, the number of locals touched by the disease will surge.
C4C is a spinoff of The Alzheimer’s Project, the San Diego County-led initiative launched last year to seek a cure and to help Alzheimer’s patients, along with their caregivers.
“No place in the world is doing more than San Diego to understand Alzheimer’s disease, and I believe we have a fighting chance right here to find a cure,” said Supervisor Jacob, who spearheaded the creation of The Alzheimer’s Project. “These research projects could make a big difference.”
Initial funds for the launch of C4C, totaling nearly $500,000, were obtained through the generosity of philanthropist Darlene Shiley and others involved with the initiative. With a five-year funding goal of $7 million, all funds will be raised through local philanthropy and restricted to projects from researchers at San Diego-based institutions.
“We have so many amazing researchers right here in San Diego, and their hard work, determination and passion give me great hope,” Shiley said. “They are doing amazing things in the laboratory, and Collaboration4Cure will help them do even more! They are breaking new ground and I’m excited to be a part of it.”
To donate to the fund, go to www.alzsd.org.
Additional projects will be authorized as earlier projects progress to more advanced phases in the drug development process.
An unprecedented local drug discovery effort led by San Diego’s premier research institutes, the city and county of San Diego, Darlene Shiley and Mary Ball, president and CEO of the Alzheimer’s Association San Diego. Through innovation and collaboration of ideas, combined with San Diego’s unique drug discovery resources, C4C plans to develop a portfolio of successful chemical compounds that can then be translated into possible therapeutic drugs to treat and or prevent Alzheimer’s disease.
Albert La Spada, MD, PhD (UCSD) Full Professor, School of Medicine, Department of Cellular & Molecular Medicine
“Modulators of Transcription factor EB (TFEB)” TFEB is a “master” controller of lysosomes, membrane enclosed packets of powerful enzymes within cells, that destroy and clear protein aggregates or “clumps”, associated with Alzheimer’s Disease (AD). Small molecules that increase the amount of TFEB or TFEB’s function in cells may thus slow the progression of AD.
Matthew Pearn, MD (UCSD) Assistant Clinical Professor, School of Medicine, Department of Anesthesiology
“Small molecules to normalize early endosome structure and function in AD” Proteins are contained and transported within cells through the coordinated maturation (early late) and movement of endosomes. In AD, accumulation and stalling of enlarged early endosomes destroy neurons. Small molecules that restore normal endosomal structure, size and function may thus prevent neuronal death in AD.
Subhojit Roy, PhD (UCSD) Associate Professor, Neuropathology, Department of Pathology
“Identifying Molecules that Attenuate APP and BACE-1 interactions”
APP (Amyloid Precursor Protein) and BACE-1 (β-site APP-cleaving enzyme-1) are membrane-bound proteins that are packaged into different “vesicles”. BACE-1 cuts APP to produce the “bad” beta-amyloid (Aβ) associated with AD. However, these two vesicles must coalesce to bring APP and BACE-1 close to each other. Small molecules that attenuate this physical convergence may provide novel ways to reduce AD progression.
Steve L. Wagner, PhD (UCSD) Associate Professor, School of Medicine, Department of Neuroscience
“Screening for Novel Gamma-Secretase Modulator Scaffolds” GSIs (“Gamma”(γ)-secretase inhibitors) block formation amyloid forming Aβ peptides, but have significant side effects they also block normal γ-secretase functions. However, small molecule GSMs (γ-secretase modulators) that reduce levels of amyloid-forming Aβ42 without affecting overall γ-secretase function may prove to be an efficacious course for interrupting AD progression.
Huaxi Xu, PhD (SBP) Program Director Neurodegenerative Disease Program, Professor, Department of Neuroscience & Aging
“Promoting TREM2 stability and activity for AD intervention” TREM2 (Triggering receptor expressed on myeloid cells 2) is a newly discovered protein mainly found on the surface of microglia, cells critical to supporting healthy neurons in the brain. TREM2 regulates key critical functions of microglia that protect neurons from inflammation and remove damaged neurons. Mutations that “knockdown” TREM2 levels or its function increase a person’s susceptibility to late-onset AD comparable to Apoε4 mutations. Therefore small compounds that can stabilize TREM2 and/or stimulate TREM2 activity may have therapeutic potential for the treatment of AD.
Elena Pasquale, PhD (SBP) Full Professor, Tumor Initiation & Maintenance Program, Cancer Center
“Inhibiting the EphA4 receptor to counteract Alzheimer’s neurodegeneration” AD-associated beta-amyloid (Aβ) in a pre-aggregated form was recently found to bind to EphA4 (ephrin receptor A4) in the brain causing neuronal death. Peptides that block this binding protect against Aβ-aggregate mediated neuron death in neuron cell culture and when infused in the mouse brain. However, peptides are too large to cross the blood brain barrier, while EphA4- Aβ binding has proven difficult to block with small molecules. In contrast, the enzymatic “kinase” region of EphA4, responsible for EphA4’s neurotoxic effects, is a highly “druggable” target. Selective and potent EphA4 kinase inhibitors would ameliorate Aβ-aggregate induced AD progression.
Lutz Tautz, PhD (SBP) Research Assistant Professor, NCI-Designated Cancer Center
“Novel screening platform to identify specific inhibitors of STEP” STEP (STriatal-Enriched protein tyrosine Phosphatase) levels and activity are increased in the human prefrontal cortex of AD patients and in four AD mouse models. Genetic reduction of STEP and small molecule STEP inhibitors lead to enhanced memory and learning abilities in an AD mice model. Tyrosine phosphatases are conventially regarded as “undruggable”, since their “active sites” are very similar. This makes it impossible to screen for or design small molecules selective for STEP alone. Our novel approach targets STEP under physiological conditions that block binding of substrate to yet unknown sites in STEP outside of their “active sites”, or interfere with STEP localization.
Yunwu Zhang, PhD (SBP) Research Assistant Professor, Department of Neuroscience and Aging
“Targeting apoptosin for intervention of Alzheimer's and other tauopathies”
Apoptosin is a recently discovered protein that governs mitochondria-mediated cellular energy production. Apoptosin levels increase in neurons treated with pre-aggregated forms of Aβ in brain samples from AD patients. Its overexpression is deleterious to neurons (increased tau cleavage, tau aggregation, and synapse dysfunction), impairs movement and exacerbates neuropathology in mice AD models. Conversely, reduced expression of apoptosin inhibits these deleterious effects. Therefore, small molecules that downregulate apoptosin may provide novel avenues for AD intervention.