2014-2015 Research Grant Awards
The LuMind Foundation announces the award of $1.1 million in funding for six new LuMind Research Grants, propelling Down syndrome cognition research. The latest recipients of LuMind 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 VA Palo Alto Health Care System.
LuMind Foundation has allocated $10.5 million in research grants since our founding in 2004.
For more detailed descriptions of the research projects, please click here.
$175,000 LuMind Research Center Grant, “A Down Syndrome Center for Fundamental Research-Cognition,” awarded to Dr. Roger Reeves, Principal Investigator, and Co- Principal Investigators Drs. David Foster and Paul Worley
Comprising multiple projects, these researchers are continuing to explore the mechanism by which a single dose treatment of SAG (an SHH growth factor-like drug) given to a mouse model of Down syndrome early in life completely restores cerebellar development and improves hippocampal function involving learning and memory associated with the developmental intellectual disability in Ds. A second study is investigating the role of altered regulation of a gene involved in synaptic plasticity related to cognition and brain network dysfunction in Alzheimer’s disease and Ds and the identification of potential new therapeutic targets. A third study concerns the development and application of a new method for real-time analysis of brain signaling that correlate with cognitive function, learning and memory which could accelerate the evaluation of the effectiveness of new drug in mouse models of Ds.
$210,000 LuMind Research Center Grant, “The Down Syndrome Cognition Project,” 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 is further developing and building on components of critical importance for a DS phenotype-specific 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.
$235,000 LuMind Research Center Grant, “Defining the genes and mechanisms and treatments for neurodevelopmental and neurodegenerative causes of cognitive dysfunction in Down syndrome,” awarded to Dr. William Mobley, Principal Investigator and Co- Principal Investigator Drs. Belichenko, Kleschevnikov, Wu, Wagner, Singhal and R. Capone.
When Dr. Mobley served as the Director of the Down Syndrome Research and Treatment Center at Stanford, he and his colleagues identified that the over-expression of the APP gene, which is located on the human 21st chromosome, is associated with impaired cognition and Alzheimer’s disease neuropathology in mouse models of Down syndrome. Follow-on research in this project continues at UCSD as investigators work to identify and investigate compounds that can regulate the proteins produced by the APP gene. 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.
$195,000 LuMind Innovation Research Grant, “The Neuropsychology of Down Syndrome,” was awarded to Drs. Lynn Nadel and Jamie Edgin, Principal Investigators.
Drs. Edgin and Nadel have developed and continue refining and validating the first set of Ds-specific battery of cognition tests (Arizona Cognitive Test Battery or ACTB, and Arizona Memory Assessment for Preschoolers and Special Populations or AMAP) that measure cognitive function involving both the developmental intellectual disability and Alzheimer’s disease in various areas of the brain affected in Ds across the lifespan. These tests also provide a way to more specifically evaluate the efficacy of potential drug treatments and other interventions to improve cognition in individuals with Down syndrome. An additional research study is exploring the development of EEG-based methodologies as potential biomarker assessments of cognitive function in individuals with Ds that can provide critical support for fundamental cognition research and clinical trials. Another research study is further extending sleep studies with the ACTB to define the relationship between sleep disturbances, including sleep apnea, and impairment of cognitive development which can provide new insights to address sleep disorders to improve cognitive function in children and adults with Ds.
$165,000 LuMind Innovation Research Grant, “Mechanisms Underlying the Roles of Sleep and Circadian Rhythms in the Learning Disability of Down Syndrome,” awarded to Dr. H. Craig Heller, Principal Investigator and Dr. Garner, Co- Principal Investigator.
In previous research supported by the LuMind Foundation, Drs. Mobley and Garner and their colleagues made a breakthrough discovery that there is too much inhibition, or “braking”, to stop or slow communications between certain brain cells (neurons) in DS. The research further showed that by limiting “inhibition”, which can overcome the imbalance in slowing or stopping the progress of communications between specific neurons, learning and memory is improved in mouse models of Down syndrome. This research provided the research basis that has led to the ongoing Roche and Balance Therapeutics clinical trials. With this grant research continues on the GABA -A receptor, a protein that plays a major part in inhibition, extending research in mouse models of Ds about how the over-inhibition may impair circadian rhythms and sleep in Ds, how this may contribute to cognitive impairment, and whether drugs that overcome the inhibition ameliorate these impairments. Follow up research is also continuing on a recent discovery of another over-expressed chromosome 21 gene, Usp16, and its potential role in deficient brain development, loss of brain cells, and early aging in Ds.
$120,000 LuMind Innovation Research Pilot Grant, “Improving Adrenergic Signaling for the Treatment of Cognitive Dysfunction in Down Syndrome,” was awarded to Principal Investigator Dr. Ahmad Salehi.
Previously, Drs. Ahmad Salehi, William Mobley and their colleagues found that a compound called L-DOPS could restore contextual learning and memory in a mouse model of Down syndrome by correcting a norepinephrine deficiency in the hippocampus. The continued research with this grant is investigating the potential for an additional existing FDA-approved drug, fomoterol, which acts as a norepinephrine mimic to restore contextual learning in the mouse DS model and also overcome the effects of the Alzheimer’s disease neuropathology in Ds on cognition. The results could provide further evidence and a rationale for accelerated clinical evaluation of this drug in individuals with Ds.