2013-2014 Grant Awards

More than $9.6 million in funding provided to date

LuMind proudly announces the award of new 2013-2014 Research Grants to fund leading researchers from major research centers around the country to help accelerate the delivery of treatments to improve cognition, including learning, memory and speech for individuals with Down syndrome. Recipients of these awards include researchers at Johns Hopkins University School of Medicine for their work with a network of institutions participating in the Down Syndrome Cognition Project; the University of California, San Diego; the University of Arizona; Stanford University; the VA Palo Alto Health Care System; and an international multidisciplinary research conference to take place in March 2014.

With the funding of its 2013-2014 LuMind Foundation Research Grants, LuMind has now provided over $9.6 million to advance Down syndrome cognition research.

Johns Hopkins University School of Medicine

$375,000 LuMind Foundation Research Center Grant awarded to Johns Hopkins University School of Medicine, Drs. Roger Reeves (Johns Hopkins) and Stephanie Sherman (Emory University School of Medicine), Principal Investigators, and 13 co-Principal Investigators with 10 research institutions across the US. The new grant is entitled “A Down Syndrome Virtual Center for Basic and Translational Studies-Cognition and Therapy in Down Syndrome.” A key feature of Down syndrome (Ds) is the high degree of variability in presentation of the various common phenotypes, especially including cognition, learning, memory and speech that characterize the syndrome. This new grant will continue to support the expansion of the Down Syndrome Cognition Project with clinical studies using Down syndrome-specific cognitive assessments, such as the ACTB, to investigate and define the variability of cognition, learning, memory and speech in individuals with Down syndrome, correlations with potentially influencing genetic factors, and contributing to further establishing a consortium of collaborating clinical sites as an important scaffold for a clinical trials network. Additionally, laboratory-based projects using mouse models for Down syndrome will continue to investigate: 1) the mechanism through which a single-dose treatment early in life with a specific SHH growth factor-like drug, SAG, restores cerebellar structure and hippocampal function involving learning and memory in adults; 2) regulation of specific gene expression affecting learning and memory function and development of hallmarks of Alzheimer’s disease; and 3) mechanisms associated with hippocampal neural network dysfunction related to learning and memory. These studies may lead to important insights for new therapeutic approaches and identify new potential therapeutic drug targets.

University of California, San Diego

$215,000 LuMind Foundation Research Center Grant awarded to University of California, San Diego, Dr. William Mobley, Principal Investigator and Drs. Belichenko, Kleschevnikov, Wu & Wagner, co-Principal Investigators. The new grant, entitled “Defining the Genes and Mechanisms and Treatments for Neurodevelopmental and Neurodegenerative Causes of Cognitive Dysfunction in Down Syndrome,” will continue investigations on how excess APP and/or its products, and potentially together with additional over-expressed genes located on human chromosome 21, lead to degeneration of specific brain circuits and Alzheimer’s disease associated pathology with age in Down syndrome. The focus of these studies includes identification and characterization of new drug targets, potential drugs, and therapeutic strategies to decrease APP and/or its products, and ameliorate age-related cognitive dysfunction and Alzheimer’s disease pathology associated with Down syndrome. An additional project involves further development of “21Lab” as a new web-based Down syndrome research “collaboratory” platform to facilitate scientific interactions among the Down syndrome research community to enhance and accelerate research progress.

University of Arizona

$195,000 LuMind Foundation Innovation Research Grant awarded to the University of Arizona, Drs. Lynn Nadel and Jamie Edgin co-Principal investigators. The new grant is entitled “The Neuropsychology of Down Syndrome.” An overarching goal is to uncover the etiological factors, i.e., genetic, neurological, medical, environmental, that lead to variation in the cognitive phenotype of Down syndrome (Ds). Identifying the factors influencing this variability with Ds-specific assessment tests will be central to the formulation and development of successful treatments for cognitive difficulties in Ds. This research supported by this new grant will continue to use and expand the Down syndrome-specific Arizona Cognitive Test Battery (ACTB) in: 1) further development of a battery for use with younger individuals with Down syndrome and validation across a wide age range; 2) investigating functional profile of the brain medial temporal lobe in learning and memory; 3) establishing biomarkers for cognitive function using the ACTB together with EEG and evoked-potential methodologies; and, 4) expanding assessments of sleep disturbance, including sleep apnea, and correlation with cognitive dysfunction in individuals with Down syndrome. These studies will further expand the application of specific cognitive assessment batteries to define cognitive function and impairments across a greater age range of individuals with Down syndrome and extend the development of biomarker assessments of cognitive function and potential associated changes as well as sleep function which could provide critical additional functional and efficacy tests for Down syndrome cognitive research and clinical trials.

Stanford University

$155,000 LuMind Foundation Innovation Research Grant awarded to Stanford University,Dr. H. Craig Heller, Principal Investigator and Dr. Garner, co-Principal Investigator. The new grant, entitled “Mechanisms Underlying the Roles of Sleep and Circadian Rhythms in the Learning Disability of Down Syndrome,” will investigate how the Down syndrome-related features of circadian rhythms and sleep are influencing learning and memory in a mouse model for Down syndrome, and how GABA-A receptor blockers may alter those relationships using EEG analysis, physiological measurements and pharmacogenetic methods. These studies could lead to greater understanding for alternative or modified treatment strategies to improve cognition in individuals with Ds, and the identification and development of potential new biomarkers that can be used to assess treatment efficacy in humans. Additional studies to normalize the over-expression of the Usp16 gene in a mouse model for Down syndrome may identify a role in reducing proliferation of brain stem cells during development and aging.

VA Palo Alto Health Care System

$115,000 LuMind Foundation Innovation Research Pilot Grant awarded to VA Palo Alto Health Care System, Dr. Ahmad Salehi, Principal Investigator. The new grant, entitled “Improving Adrenergic Signaling for the Treatment of Cognitive Dysfunction in Down Syndrome,” will extend ongoing studies involving the use of specific drugs which increase norepinephrine (NE) signaling in the brain, including determining effective dosages, to improve learning and memory in a mouse model for Down syndrome as well as how these drugs may positively impact hippocampal neurogenesis, alter neurodegeneration and improve associated cognitive function. These studies will contribute to advancing research and development of potential NE- based therapies for cognitive disabilities in Down syndrome, including aspects related to Alzheimer’s disease.

Research Conference Grant

$10,000 LuMind Foundation Research Conference Grant awarded for “Alzheimer Disease in Down Syndrome: From Molecules to Cognition,” an international research conference, Cambridge UK, March 26-29, 2014. This multi-disciplinary research conference will focus on further defining the links between Down syndrome and Alzheimer’s disease, understanding dementia in Down syndrome at the neurological, cognitive, behavioral, cellular and genetic levels, and strategies for the development of effective therapies.

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