2015-2016 Research Grant Awards

The LuMind Research Down Syndrome Foundation announces the award of $1,415,000 in funding for six new Research Grants, propelling Down syndrome cognition research. The latest recipients of LuMind RDS Foundation grant funding are researchers at Johns Hopkins School of Medicine, Emory University School of Medicine, University of California San Diego School of Medicine, University of Arizona, Stanford University and Palo Alto Veterans Research Institute/VA Palo Alto Health Care System.

LuMind RDS Foundation has awarded more than $13.2 million in research grants since our founding in 2004.

Johns Hopkins University School of Medicine – A Down Syndrome Center for Fundamental Research-Cognition

$227,500 Research Center Grant awarded to Dr. Roger Reeves, Principal Investigator, and Co- Principal Investigators Drs. David Foster and Paul Worley.

Comprising multiple projects, the first project (Reeves and collaborators) involves further investigation of the mechanistic basis by which a single-dose treatment with SAG (an SHH growth factor-like drug), early in life of a mouse model of Ds restores cerebellar structure and hippocampal function involving learning and memory in adults. A second project (Worley and collaborators) further investigates the role of NPTX2 (Narp) down regulation in Ds in abnormal synaptic transmission and how this may alter excitatory-inhibitory balance and the development of AD pathology in humans and mouse model of Ds. An additional project led by Foster and collaborators, continues to develop novel electrophysiological method for real-time detection of hippocampal neural circuit/network communication dysfunction and pharmacological-mediated changes related to cognition.

Emory University School of Medicine – The Down Syndrome Cognition Project

$275,000 Research Center Grant  awarded to Drs. Stephanie Sherman (Emory) and Roger Reeves (Johns Hopkins), Principal Investigators, and  Co- Principal Investigators at eight additional institutions:  Kennedy Krieger Institute, University of Arizona, University of California Davis/MIND Institute, University of Pittsburgh, Oregon Health and Science University, Children’s National Medical Center Washington DC, University of Pennsylvania/ Children’s Hospital of Philadelphia, Waisman Center/University of Wisconsin.

The research goals of The Down Syndrome Cognition Project (DSCP) are to understand the genetic contribution to the substantial variation in cognitive ability among individuals with Down syndrome using the Arizona Cognitive Test Battery (ACTB), identify targets for therapeutic interventions and establish a network of collaborating clinical sites as an initial scaffold for a clinical trials network. This research further develops and builds on components of critical importance for a Ds-specific phenotype and genotype research database and associated biorepository, advancing validation of the ACTB as specific new biomedical standard and critical efficacy assessment component in clinical trials, expanding clinical sites and facilitating increased DS-Connect registration.

University of California San Diego School of Medicine – Defining Genes, Mechanisms and Treatments for Neurodevelopmental and Neurodegenerative Causes of Cognitive Dysfunction in Down Syndrome

$325,000 Research Center Grant awarded to Dr. William Mobley, Principal Investigator and Co- Principal Investigator Drs. Kleschevnikov, Wu, Wagner, and Singhal.

The research extends investigations on the over-expression of the APP gene, which is located on the human chromosome 21 and associated with impaired cognition and Alzheimer’s disease neuropathology in mouse models of Down syndrome.  A fundamental goal of the research is to determine the mechanisms by which APP acts to disrupt the endocytic pathway and the trafficking of neurotrophic signaling in Ds and contribute to neurodegeneration and AD pathology with aging. A major focus includes research to identify and investigate compounds that can regulate the proteins produced by the APP gene and prevent or halt the associated age-related neurodegeneration and cognitive decline. Further studies focus on identification of additional over-expressed chromosome 21 genes involved in the age-dependent development of Alzheimer’s disease related to endosomal signaling dysfunction in nerve cells and their role in neurodegeneration and cognitive dysfunction in mouse DS models which may lead to the identification of new drug targets, potential drugs, and therapeutic strategies to improve cognition.

University of Arizona – Brain Development, Sleep and Learning in Down Syndrome

$250,000 Innovation Research Grant was awarded to Principal Investigator Dr. Jamie Edgin and Co-Principal Investigators Drs. Nadel, Gomez, and Clark.

A major goal of this research is to uncover etiological factors (genetic, neurological, medical, environmental) leading to variation in the cognitive phenotype of Ds through the development of reliable, valid Down syndrome-specific assessments, such as the Arizona Cognitive Test Battery (ACTB), of key components of cognition in children and adults with Ds. The researchers will continue to validate and refine an additional new battery extending to much younger children and aged individuals (A-MAP, the Arizona Memory Assessment for Preschoolers and Special Populations). An important objective is to establish such assessment batteries for use in clinical trials to determine efficacy of new therapies in improving cognition across the lifespan of individuals with Ds. Research will also continue on the development of EEG-based methodologies as potential biomarker assessments of cognitive function in individuals with Ds that provide critical support for fundamental cognition research and clinical trials. The researchers are  further extending studies on sleep disturbances and obstructive sleep apnea in the Ds population, specifically focusing on how sleep disruption contributes to learning delays and formation of long-term memories in young children and adults with Ds and defining the specific aspects of sleep physiology that underlie these associations.

Stanford University – Mechanisms Underlying the Roles of Sleep and Circadian Rhythms in the Learning Disability of Down Syndrome

$197,500 Innovation Research Grant awarded to Dr. H. Craig Heller, Principal Investigator and Co-Principal Investigators Drs. Garner and Adorno.

A primary goal of one aspect of this research, using mouse models of Ds, is to more deeply understand the basis of the learning disability in Ds through investigating the role of disruption of specific brain wave oscillations (communications) involved in the transfer of information between the hippocampus and the cortex in the brain and associated with sleep and the formation and retention of long-term memories. An additional research project will further investigate the role of the over-expression of the Usp16, a human chromosome 21 gene, in the regulation of brain stem cells during development and aging in mouse models of Ds and its involvement with reduced brain cell numbers, atypical brain development, including early aging, and cognitive dysfunction. The researchers will also examine whether reduction in Usp16 expression may overcome these impairments and lead to identification of new drug targets and therapeutic approaches for individuals with Ds.

Palo Alto Veterans Research Institute/VA Palo Alto Health Care System  – Improving Adrenergic Signaling for the Treatment of Cognitive Dysfunction in Down Syndrome

$140,000 Innovation Research Pilot Grant was awarded to Principal Investigator Dr. Ahmad Salehi.

Previously, these researchers discovered that drugs such as  L-DOPS and formoterol, each developed and approved by the FDA for other medical conditions, could restore contextual learning and memory in a mouse model of Ds by correcting a deficiency in norepinephrine input to the hippocampus caused by the degeneration of a specific brain pathway designated the locus coeruleus. The continued research with this grant is investigating, in a mouse model of Ds, the potential for lower therapeutic dosages of either of these drugs in synergy with physical exercise to effectively restore contextual learning and memory, improve trophic factor signaling and also overcome the progression and effects of neurodegeneration associated with the Alzheimer’s disease neuropathology in Ds. The results could provide further evidence and a rationale for accelerated clinical evaluation of these drugs in individuals with Ds.