In a cooperative effort that promises new targets for effective therapeutics for amyotrophic lateral sclerosis (ALS), the ALS Association (ALSA) recently announced funding of a search for genes involved in the sporadic form of the disorder in people who have no family history of the disease. The study uses the most up-to-date technology of gene finder chips
The search will use the newly established DNA banking project-a repository of samples from patients and healthy people for comparison-made possible through the National Institute of Neurological Disorders and Stroke (NINDS). At the National ALS Advocacy Day and Public Policy Conference held on May 15-17, 2006, in Washington D.C., ALS patients and caregivers participated by anonymously donating a small amount of blood and providing a clinical history. In order to protect privacy, none of the gathered information allows the donors to be individually identified.
Investigators Bryan Traynor, M.D., a fellow at the National Institute of Mental Health, and John Hardy, Ph.D., of the National Institute on Aging (NIA), will lead the joint effort with NINDS and the Robert Packard ALS Center at Johns Hopkins University. The work will be carried out at the NIA Neurogenetics Laboratory, Bethesda, Md.
"We are extremely pleased to have such an excellent team for a partnership that is truly using cutting edge technology," said Lucie Bruijn, Ph.D., ALSA science director and vice president. "This effort should make a real difference for sporadic ALS and is the kind of project that the patient DNA repository was put in place to serve."
Bruijn noted that the information gathered by the partnership will be made readily available to other scientists in the field.
ALS is inevitably fatal and despite numerous research advances no treatments have been found. It remains a mystery why nerve cells that supply muscles die in the disease. Scientists are still challenged to come up with an effective, targeted therapy.
In the decade since the discovery of a mutation in the protein copper-zinc superoxide dismutase (SOD1), the cause of some inherited forms of ALS, several more mutations have been brought to light. Finding genes that contribute to the disorder undoubtedly will provide new targets for therapeutic candidates. The genetic underpinnings of sporadic ALS-the disease that for 90 percent of ALS patients appears to occur spontaneously without family history-remain even more unclear. Even though inherited ALS is clinically indistinguishable from sporadic ALS, the same genes may not be responsible for both. But something that is common to both forms of the disease is the way that motor neurons die. That is why a gene change identified in one type can help understand the other.
Is sporadic ALS due to a gene change, several gene changes that interact, an environmental exposure, or some combination of these factors? Traynor and Hardy will take on the challenge of sporadic ALS directly by using the newest technology to search through the entire genome of more than 500 people who will contribute samples. Thanks to the Human Genome Project and a new technology that accelerates the ability to sift through the genome, the ability to seek signposts of gene change among samples from many people at once should help address the mystery behind sporadic ALS.
The team will search through variations in the genes called single nucleotide polymorphisms (SNPs). These SNPs each represent an instance where the genetic code for an individual has a difference at one particular base in the DNA. The Human Genome Project identified large numbers of SNPs distributed among the genes in humans. SNPs can serve as signposts on chromosomes of places that could end up including a gene linked with ALS. SNPs tell scientists where in the vast genome to start looking. The investigators will carry out automated analysis of samples collected by the ALS Biomaterial and Data Banking initiative, part of the NINDS Human Genetics Repository, using the newest SNPs on a chip. A SNP chip is a device similar to a computer chip that can read known SNPs in the human genome. The technology to be used in the effort offers unprecedented detailed analysis of the SNPs present in the human genome. Operated by robotics, a search through 276 U.S. ALS patient samples and 276 European patient samples should produce important new information on what genetic influences might be producing sporadic ALS.
Because the NINDS repository includes data on the symptom onset, progression, laboratory findings, and other features of the illness, and in normal subjects, detailed medical and family history, the DNA samples will be analyzed with correlations to clinical symptoms adding to the strength of this study.