The Robert Packard Center for ALS Research at Johns Hopkins

Projects Funded by the 2006 Wings Over Wall Street

INVESTIGATOR	PROJECT	COST	SUMMARY
Philip C. Wong, PhD	Development of transgenic mice carrying dynactin mutations associated with sporadic ALS	$54,000	Mutations in the gene for dynactin, part of the protein motor that drives a cell’s transport system, are suspect as a cause of ALS. In a recent review of more than 2,000 patients and controls, however, effects of various dynactin mutations weren’t obvious. So a more direct approach using mutation-bearing mouse models capable of thorough analysis should clarify effects. This approach could be especially helpful in explaining mechanisms of sporadic ALS.
Alex Kolodkin, PhD & Thomas Lloyd, MD, PhD	A drosophila model of motor neuron disease using mutations in p150 dynactin	$64,800	The fruitfly, Drosophila melanogaster, has helped reveal new drug targets for neurodegenerative diseases by modeling their key molecular signposts, then serving as subjects in rapid, high-volume drug testing. The goal of this project is to create a genetic model of motor neuron disease in Drosophila and then use this model to search for new drug targets for ALS.
Shan Sockanathan, PhD	Retinoid-dependent mechanisms of spinal motor neuron specification & function	$86,400	Retinoic acid (RA) signals are essential in spinal motor neuron development. RA regulates two genes, we’ve found, each active at different times in developing motor neurons. The genes’ protein products may critically affect spinal motor neuron differentiation and behavior. We intend to test this hypothesis in motor neurons either by eliminating or increasing the gene product levels and noting effects on motor neuron development.
Hongjun Song, PhD	Development of ALS models using embryonic stem cells (renewal)	$91,800	In this project, we’ll create ALS models via human embryonic stem cells with the hope of revealing as yet undiscovered mechanisms of human motor neuron decline and death. The study complements ongoing research using rodent models. Useful reagents will also be generated for the ALS research community for use in studies to clarify disease mechanisms as well as screen for therapeutic drugs.
John Griffin, MD	New tool for the assessment of the pathology of experimental motor neuron disease	$95,716	We’ve developed new techniques that rapidly and efficiently survey the pathology of the human peripheral nervous system, approaches that could translate well to the study of models of motor neuron disease. We’ll adapt them to develop simple, rapid methods any investigator can use to characterize peripheral nervous system pathology in rodent models of motor neuron or PNS disease.
Nicholas Maragakis, MD	A non-neuronal, human cell-based transplantation paradigm targeting respiratory dysfunction in ALS	$91,800	This project uses a rat model of ALS to investigate transplantation of human glial stem cells as a means of protecting the body’s own motor neurons from dying.
Bryan Traynor, MD	Follow-up genetic association study of sporadic ALS using the Illumina iSelect custom SNP chip	$154,090	To clarify the genetic basis of sporadic ALS, a large number of variable DNA sites (SNPs) potentially associated with an increased risk of sporadic ALS were identified in our initial surveys --- genome wide association screens --- of American and Italian populations. Because determining which of the SNPs are genuinely associated with ALS risk, it’s necessary to screen for them in a larger, new sample of American and European cases and controls. This project will determine which of the 6,200 most associated SNPs identified in the original whole genome association studies are genuinely associated with an increased risk of ALS.