Calabasas Hills, CA (July 16, 2002) - The ALS Association (ALSA) today announced it has embarked on an unprecedented effort to identify new genes linked to familial ALS, applying the same technology as that used in the Human Genome Project and involving renowned leaders in genome and ALS research. The ALS Association is committing a minimum $1.5 million to this Gene Identification Project.
"The discovery of more genes linked to ALS is crucial for our understanding of disease mechanisms and may provide new targets for therapy, " said Lucie Bruijn, PhD, Science Director and Vice President of The ALS Association. She points out that the discovery of several genes in familial Alzheimer's disease all involved a common pathway, which has enabled the pharmaceutical industry to focus on this pathway to develop therapies.
Traditionally, geneticists use the "candidate gene approach" to finding new disease-linked genes. In an attempt to dramatically hasten the gene identification process, this collaborative effort will capitalize on the advances in sequencing technology to rapidly sequence large regions of the chromosome linked to familial ALS. If successful this approach will have major implications on the identification of gene mutations in other diseases.
"Using the same technology as that used in the Human Genome Project enables us to more systematically and rapidly sequence through large regions of the genome to identify genes linked to disease, It's more efficient and cost effective," says Dr. Eric Lander, director of the Whitehead Institute Center for Genome Research, who will spearhead this effort. "Also, using genomic DNA from ALS patients is the most direct and reliable way to identify ALS-linked genes."
The discovery of the Cu/Zn superoxide dismutase 1 (SOD1) gene on chromosome 21 linked to 20% of familial ALS (FALS), almost a decade ago made a major impact on ALS research. The development of an animal model, now the standard for testing possible therapies for ALS, enabled scientists to begin to test a variety of disease hypotheses. ALSA was a major contributor in the initial discovery and has funded many of the follow-up research studies to date. Yet, genes linked to the remaining 80 percent of familial ALS remain unknown.
Adds Bruijn, "The discovery of new disease-linked genes will provide important information in understanding not only the mechanisms of cell death in familial ALS, but also sporadic ALS which accounts for 90 percent of all ALS cases."
Dr. Robert Brown of the Massachusetts General Hospital concurs, saying "There is no doubt that discovery of new causes of familial ALS will illuminate our understanding of non-familial ALS. It is even possible that the new insights will be relevant to other brain degeneration diseases. This initiative will ultimately be important in devising new ways to treat ALS."
The participants in this project include Dr. Robert H. Brown, Jr., of Massachusetts General Hospital, Dr. Guy Rouleau of Montreal General Hospital, Dr. Jackie de Belleroche of Imperial College, Charring Cross Hospital, London, England, and Dr. Teepu Siddique of Northwestern University, who will contribute family resources. Dr. Pieter J. de Jong of the Children's Hospital Oakland Research Institute, will generate BAC libraries from FALS hybrid cell lines prepared for each of the families through GMP Companies, Inc., and Dr. Eric Lander of the Whitehead Institute Center for Genome Research, will direct the sequencing of the selected BAC clones from these libraries.
"This international collaboration to identify new genes linked to familial ALS is among the most exciting and potentially informative projects we have initiated", says Dr. Tom Maniatis, head of ALSA's Cure ALS Advisory Committee. "We are very fortunate to have the outstanding geneticists who have identified new ALS loci working closely with scientists who played central roles in sequencing the human genome. If successful, this effort will not only identify ALS genes associated with currently identified familial loci, but will advance the technology required to identify additional ALS genes in the future."
The technology to be used is as follows:
* Development of BAC libraries from familial ALS patients -- This technology prepares the large regions of a chromosome (loci) in such a manner that they can be effectively sequenced. Pieter de Jong, PhD, will spearhead this effort. ALSA anticipates that four BAC libraries covering portions of two chromosomes will be prepared. BAC is an acronym for "Bacterial Artificial Chromosome," a vector used to clone DNA fragments in E. coli cells.
* Sequencing of BAC libraries to identify gene mutations linked to the disease - As two libraries are completed, they will go into Phase II for sequencing. Eric Lander, PhD, will direct this effort.