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It’s How We Work
Last fall, Bryan Traynor and John Hardy ran their idea for a “whole-genome association study” past Center Director Jeff Rothstein. Their proposal for a high-tech analysis of the DNA of thousands of patients and healthy volunteers offered the largest step ever to unmask the biology of sporadic ALS. The Packard scientific advisors agreed, and in two months, the NIH scientists became grantees with funds in hand and access to a well of advice. The NIH supplied leading-edge gene chips, a DNA bank and lab support.
Traynor and Hardy’s first results last April reported 32 places where patients’ DNA differed from healthy volunteers’. The necessary follow up study adds gene chip data from more than 2,000 new people to show which leads to follow.
Center Stats
- Since 2002, Center scientists have parlayed sound research from roughly $12 million in Packard “seed money” into some $100 million in NIH funding.
- Our 38 scientists account for nearly 75 percent of ALS research published in top journals.
- This year, 15 studies were funded by the Center in collaboration with the ALS Association, the Muscular Dystrophy Association, the NIH and the Brain Trust Initiative.
- Since the Center’s inception, academic-instigated clinical trials for ALS have doubled, with a 50 percent increase in trial participants.
The Theories Are Ours
Center research underlies the major existing theories on ALS—evidence that informs the therapeutic approaches we explore:
- The “neighborhood effect” – ALS isn’t solely a disease of motor neurons. There’s an interplay with other nervous system cells and muscle.
- Protein aggregation – Similar to Alzheimer’s disease, clumps of malformed protein parallel ALS severity.
- Axon transport – ALS disrupts a motor neuron’s internal circulation.
- Dying-back biology – ALS affects the far ends of motor neurons well before symptoms appear. This “dying back” could buy time for protective therapy.
- Excitotoxicity – We’ve uncovered key reasons why motor neurons become vulnerable to injury by overstimulation in ALS.
- Mitochondria gone awry – ALS damages the cell’s “powerhouses” in characteristic ways.
A Model Situation
The majority of ALS animal models—the best way to study the disease and possible therapies—come from Center labs. We’ve developed:
- More than a dozen mSOD1 rodent models
- The ALS zebrafish
- The dynactin mouse/ the dynactin fruit fly
- Mouse models with almost every known ALS gene including ALS2, ALS4
Therapeutics: Cellular and Drug
All our efforts, ultimately, are geared toward therapy.
- We’re first to use motor neuron/astroglia stem cells to alter disease
- We’ve gotten stem cells to develop into muscle-contacting motor neurons
- We’re using natural trophic factors to encourage repair/protect neurons
- We’re developing gene therapy approaches
- We implement large-scale high and low throughput drug discovery
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