Research News
The mission of P2ALS is to fast-forward the most promising ALS research toward the first effective therapies. The three-year venture unites leading researchers and clinicians and eighteen partner laboratories from The Packard Center for ALS Research at Johns Hopkins University and Project A.L.S. P2ALS exemplifies the power of collaboration, not only for the sake of studying ALS—but treating and curing it.
P2 ALS Drives Breakthrough in Understanding of Sporadic Disease
Astrocytes derived from patients with sporadic ALS
A study led by P2 ALS team member Brian Kaspar and published in the August 10 online issue of Nature Biotechnology, shows that brain cells called astrocytes derived from patients with sporadic ALS are toxic to motor neurons, the very cells targeted for destruction in ALS.
Dr. Kaspar’s findings provide scientists with a new window onto potential causes of sporadic and familial ALS, as well as targets for new therapies. P2 ALS collaborators are currently working to identify the exact nature of this toxicity. A more complete understanding of the relationship between different types of brain cells in ALS will provide new opportunities for drug screening.
For nearly two decades, scientists have tested potential ALS drugs in mice that are bred to develop a fast-acting form of familial (SOD1) ALS. While invaluable, the SOD1 mouse has not necessarily helped us to identify drugs that work in people with either the familial or the much more common “sporadic” form of the disease. P2 ALS has contributed history’s first models of human ALS to the field by exploiting a new technology call iPS, or pluripotent stem cell technology. iPS technology allows scientists to generate unlimited motor neurons and astrocytes from the skin of ALS patients.
P2 ALS is an accelerated research initiative between Project A.L.S. and the Packard Center for Research at Johns Hopkins whose mission is to identify and validate new therapeutic targets in ALS.
P2 ALS: Eye on Therapeutic Targets
P2 ALS Co-directors (left to right): Daniel L. Doctoroff; Dr. Robert H. Brown Jr.; Dr. Jeffrey Rothstein; Dr. Zach Hall; and Dr. Thomas M. Jessell
January, 2011 – At the conclusion of a meeting in New York this January, the directors of P2 ALS, a dynamic, three-year mission uniting complementary research efforts at Project A.L.S. and The Packard Center for ALS Research at Johns Hopkins, summarized significant progress at the close of Year 1 of the initiative, and announced Year 2 milestones. Researchers from all 18 P2 ALS laboratories nationwide were on hand for a wide-ranging, targeted discussion of the initiative’s urgent goal: the identification of therapeutic targets. The translational strategy of P2 ALS has become more focused through intensive collaborations among the 18 partner labs to utilize ongoing genetic and mechanistic research internally toward (1) Target discovery (2) Target validation (3) Preclinical development. The P2 ALS team has already identified new candidate genes and is homing in on mechanistic targets based on motor neuron degeneration and glial toxicity in ALS. “The drug discovery process is too long as it is,” said Valerie Estess, a P2 ALS administrative director. “The extra insult with ALS is we’ve never had reliable targets to hit with drugs. P2 ALS will change that.”
Two Project A.L.S. Studies Confirm Reliability of Human iPS Cells,Opening Door for ALS Modeling and Drug Screening
February 4, 2011 – In two compelling studies published online, a team of scientists from the Project A.L.S./Jenifer Estess Laboratory for Stem Cell Research, the Broad Institute,
Harvard Stem Cell Institute, the Motor Neuron Center at Columbia University, and the
Howard Hughes Medical Institute, among other institutions, announced that it has established reliable procedures for evaluating the efficiency of differentiated induced pluripotent stem (iPS) cell lines and embryonic stem (ES) cell lines, and have begun using the cell lines to model ALS, a fatal neurodegenerative disease, more reliably in the laboratory.
View the complete Cell article
View the complete Nature Biotechnology article
View the full Project ALS™ Press Release
SOD1 Gene Implicated in Familial and Sporadic ALS
October 17, 2010 – Until now, the mutation to the gene SOD1 has been associated with a small number of inherited cases of ALS. Now Project A.L.S. researcher Robert H. Brown, Jr., and colleagues at University of Massachusetts, have identified a potential role for the gene in sporadic forms of the disease. Discovery of this common pathology is described in the October 17 online edition of Nature Neuroscience.
The identification of this common pathology may open the door for new therapeutic approaches. For example, scientists working on SOD1 gene silencing for familial ALS can now think about applying the promising strategy to other, more common forms of the disease.
View Dr. Brown's paper
View summary of findings
New Drug Screens Begin at Project A.L.S. Stem Cell Lab
October 18, 2010 – For years, people have tried to develop effective drugs for ALS, with limited success. One reason for the dearth of drug discovery is that the models of ALS against which drugs and compounds are screened are not reliable—they do not mirror human ALS accurately. A platform called iPS—induced pluripotent stem cells—is changing the way we screen drugs and chemical compounds for ALS. At the Jenifer Estess Laboratory for Stem Cell Research, collaborators from Project A.L.S., Columbia University, Harvard University, and Johns Hopkins, are using iPS cells derived from ALS patient skin to recreate live-cell representations of human ALS in each of the 360 small wells on a slide. Utilizing various screening tools, including the Plate Runner HD ©, developed by the company Trophos, Project A.L.S. has undertaken an aggressive screening of potentially neuroprotective agents.
Motor Neurons of All Kinds Generated from Stem Cells
September 3, 2010 – From head to toes, different muscles in our bodies are stimulated by dozens of different subtypes—or pools--of motor neurons. Hynek Wichterle, a Project A.L.S. scientist at Columbia University, and his group, now show that these motor neuron subtypes can be generated from stem cells.
Featured as the cover story in this month’s Cell Stem Cell, Dr. Wichterle’s groundbreaking study indicates that ES cells can be programmed in a predictive manner to acquire the molecular and functional properties that characterize these motor neuron pools.
This breakthrough makes possible several new approaches to ALS therapies. For example, if we are able to generate motor neurons that control breathing, we may better approach strategies toward prolonging respiratory function in people with ALS.
Leading Researchers Unite for P2 ALS, a 3-Year Mission to Understand and Treat the Neurodegenerative Disease
January 29 2010 — Project A.L.S.™ (New York, NY) and the Robert Packard Center for ALS Research at Johns Hopkins University (Baltimore, MD) announced that they will partner on P2 ALS, a $15 million initiative designed to advance ALS (Lou Gehrig’s disease) research exponentially over the next three years.
Project A.L.S.™ and the Packard Center, non-profit leaders in forging productive collaborations among research scientists, will focus jointly on identifying the underlying causes of and the first effective treatments for ALS, a uniformly fatal neurodegenerative disease that is closely related to Alzheimer’s, Parkinson’s and Huntington’s diseases. Co-scientific directors of P2 ALS are Robert H. Brown, Jr., M.D., D.Phil. (University of Massachusetts), Thomas M. Jessell, Ph.D. (HHMI/Columbia University), and Jeffrey Rothstein, M.D., Ph.D. (Johns Hopkins University).
P2ALS is distinctive in that it unites key world leaders in the three disciplines that have recently transformed the landscape of ALS science: Genetics, Stem Cell Reprogramming, and Glial-Neuron Signaling. Through P2ALS, targeted research in these three areas will be performed in an interactive, collaborative, and transparent manner. As such, the implications of discoveries in one area will be rapidly transmitted and tested in complementary areas, by multiple laboratories. New observations and ideas can and will be validated or refuted with unprecedented speed.
View the Project A.L.S.™ press release
SCIENTISTS DISCOVER A NEW ROLE FOR INTERNEURONS: MODULATING THE PERFORMANCE OF MOTOR NEURONS AND MUSCLES
Major Implications for ALS
It is well established that motor neurons send signals directly to muscles to make them contract. In the December 10, ‘09 issue of the journal Neuron, Project A.L.S.™ scientists led by Laskaro Zagariou, Robert Brownstone, Tom Jessell and Gareth Miles, identify C boutons, aspects of spinal interneurons, as "volume dials" for motor neurons. This discovery gives scientists a more complete picture of how the brain talks to muscles all over the body.
"The more we know about normal brain circuitry, the more effectively we can strategize therapeutics for a nervous system that is under attack by ALS," says Valerie Estess, director of research for Project A.L.S.™
View the complete article in Neuron
View the preview article in Neuron
