Eleanor and Lou Gehrig MDA/ALS Research Center Projects Proposal Funded by MDA's Wings Over Wall Street® 2005 Fund Raising
Principal Investigators	Project	Total Amount	Major Goals
Hiroshi Mitsumoto, MD Petra Kaufmann, MD, MS Paul Gordon, MD Rochelle Goldsmith, PhD Regine Santalla, Phd	Oxidative Stress in ALS	$67,885	To identify the best the measurement methods for oxidative stress markers in ALS To study oxidative stress with prolonged exercise stress in patients with ALS To measure changes in oxidative stress markers with anti-oxidative treatment, CoQ10
Paul Gordon, MD Hiroshi Mitsumoto, MD	Phase II Combination Drug Selection Trial	$50,000	Compare in human ALS the neuroprotective potential of two combinations of agents that influence different mechanisms of neurodegeneration. Test an important new phase II selection trial design to determine which combination is superior. Purchase drug for the clinical trial Hold investigator and coordinator start-up training meeting Design data management system for the trial Obtain FDA IND, IRB and DSMB approval for start-up
Robert Basner, MD Hiroshi Mitsumoto, MD Paul Gordon, MD	A Prospective Study of Bilevel Positive Airway Pressure vs Volume Cycled Ventilation	$67,885	To test the hypothesis that nocturnal NIPPV with a volume cycled ventilator results in a slower decrement in vital capacity, muscle strength, a longer survival and better quality of life as compared to pressure ventilator. To assess the major variables which may discriminate between the efficacy of the 2 different modes of nocturnal ventilation.
Paul Gordon, MD Karen Marder, MD	Study of Cognitive Impairment in ALS	$50,000	Conduct a longitudinal study, collecting data on cognitive dysfunction from a large clinic population of patients with ALS. Determine indicators of prognosis, the clinical impact of changes in cognition, and best measures of cognitive impairment in this population. Determine whether changes in cognition correlate with motor decline and vice versa, and determine pathological correlates of clinical cognitive dysfunction, Pilot eye movement assessments of cognitive changes in patients with advanced ALS Design a clinical trial for a subgroup of patients with cognitive impairment, Reach a definition of dementia and cognitive impairment in ALS.
Christopher Henderson, Ph.D.	Mechanisms of motor neuron cell death in ALS	$55,000	To confirm the involvement of a novel, motor neuron-specific, cell death mechanism in motor neuron death in vivo To test the effects of crossing mutant mice for Fas signaling with ALS mutant SOD mice
Thomas Jessell, PhD	Genetic Determinants of Motor Neuron Identity	$55,000	Characterization of motor neuron columnar subtypes in vivo through expression of Fox genes (with J Dasen). Characterization of motor neuron pool subtypes in vivo through expression of Hox genes (with J Dasen) Differentiation of mouse ES cells into motor neuron subtypes (with H Wichterle)
Andreas H. Kottmann, PhD	Function of wfs1 in Cranial and Spinal Motor Neuron Maintenance	$55,000	Determine sensitivity of motor neurons towards exitotoxins and physiological stressors as a function of wfs1 gene dosage in primary cultures. Determine kinetics and quality of motor neuron differentiation and maintenance in the absence of Wfs1 utilizing ES cell lines derived from Wfs1-/- mouse embryos.
Serge Przedborski, MD, PhD	ER stress and NOGO pathway	$55,000	Determine the molecular machinery involved in SOD1 entry in the ER Assess the effects of modulating the expression of ER chaperon on cell survival Examine the impact of up-regulation of ER chaperon on mutant SOD1 turnover