The entire spectrum of genes involved in the origin and development of multiple sclerosis is close to being identified, according to a team of researchers at a Swiss-based pharmaceutical company.1
An Advance in Genetics
Scientists at the Serono Genetics Institute in Paris announced this month that they're developing a register of all the genes that play roles in the disease. The institute is a research arm at Serono, a biotechnology firm that markets two medications for multiple sclerosis: Novantrone (mitoxantrone) and Rebif (interferon beta-1a).
Why is this project important? For one thing, genetics plays a significant role in the disease. For example, in the general population, your odds of developing any disease are much lower than if your family member contracted it, explained Steve Arkinstall, PhD, Head of Discovery at Serono, in an interview with Priority Healthcare.
"While genetics may not be the whole story, it still dictates to a large part those people who are susceptible to getting a disease and those who are not," he explained.
Understanding genetic patterns in the pathology of MS is also important for developing medications that may target mutations, or abnormalities, in certain sets of genes that lay at the heart of MS development.
But up until now, targeting the genes that underlie the disease hasn't been easy, Arkinstall explained, because unlike diseases in which a single abnormal gene may be the cause, MS involves large sets of genes that interact with each other. Identifying them has been made easier because "technologies have evolved to a point where we can now start to do very, very rapid analysis of the genome in people, and identify genes which are altered in patients versus those that are not altered in people who don't get the disease," he said. "So you can start to draw associations between genes and the incidence of the disease."
Breaking New Ground
For the first time, 80 genes involved in the inflammatory and neurodegenerative pathways of multiple sclerosis (MS) are being identified. The research team is accomplishing this by comparing the genetic profile of 900 people with MS, then comparing them to an equivalent number of healthy individuals in different populations. The project is being conducted in three countries, including the United States.
"We are excited about this significant step forward in building a complete inventory of genes involved in MS," said Daniel Cohen, vice-president and Worldwide Head of Genetics at Serono, in a statement. "The completion of the MS Whole Genome Scan in 2006 will lead to a comprehensive catalog of potential MS drug targets, providing a basis for the future development of innovative MS therapies."
Drug Development Implications
By completely identifying the entire set of genes involved in the development and progression of MS, medical researchers will then be able to identify proteins that can be used either as targets for drug development or directly as therapeutics. Additionally, increasing knowledge about genetics in MS provides a basis for designing safer and more effective medications for the disease. Harnessing this knowledge can also help medical experts develop treatments that are better customized to an individual patient, Serono stated.
Developing drugs as a result of broadened knowledge about the role of genes and/or proteins in disease is known as targeted therapy. These drugs are designed to selectively target the molecules that play key roles in the progression of disease. Targeted therapy has been a hot topic of late in the medical literature relative to cancer.2-4
Scientists have also underscored the importance of developing targeted therapy for MS, as well. "We are beginning to understand that, analogous to cancer therapy, the successful therapeutic strategy in multiple sclerosis might ultimately involve the combination of different therapeutics targeting several dominant pathophysiological processes," wrote Bibiana Bielekova, MD, and Roland Martin, MD, both with the Neuroimmunology Branch at the National Institutes of Health in a 2004 paper on the topic.5 "The development of these process-specific therapies will be impossible without the use of biomarkers that reflect the targeted process, [and which] can select patient populations in which the targeted process is prevailing, and can aid during the more rapid screening of therapeutic agents in the early phase of their development."
In fact, drug discovery research is being conducted at the Serono Pharmaceutical Research Institute in Geneva, running concurrently with the genome project, Arkinstall explained.
In the meantime, the genome project at Serono continues. The ability to more rapidly identify large sets of genes in the disease is a major accomplishment, he said. "That’s an enormous advantage and head start over anything we've had in the past."
1. Serono Announces Major Milestone in Identifying the Genes Involved in Multiple Sclerosis. Press Release. Serono. 2005 Mar 17.
2. Kuwano M, Fujii T, Ono M, Izumi H, Kohno K. Molecular targeting drugs—present status and future development [Translated from Japanese]. Noppon Rinsho 2004 Jul;62(7):1211-5.
3. Seeman S, Maurici D, Olivier M, de Fromentel CC, Hainaut P. The tumor suppressor gene TP53:implications for cancer management and therapy. Crit Rev Clin Lab Sci 2004;41(5-6):551-83.
4. Opalka B, Dickopp A, Kirch HC. Apoptotic genes in cancer therapy. Cells Tissues Organs 2002;172(2):126-32.
5. Bielekova B, Martin R. Development of biomarkers in multiple sclerosis. Brain 2004 Jul;127(Pt 7):1463-78. Epub 2004 Jun 4.
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include coverage of health news for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
