Live Long and Prosper

A start-up company aims to extend human longevity and improve older people's quality of life by designing medications that target mutant genes.

By Judy Siegel-Itzkovich

"Ashkenazi Jews, who have been endogamous for nearly 2,000 years, are one of the best groups for this kind of research," says Dr. Ariel Darvasi, president and chief scientific officer of IDgene, a highly regarded genomics company in Jerusalem with a staff of 40 including geneticists, molecular biologists, and computer experts. "The unique demographic history of the Jewish Ashkenazi population includes emergence from a limited number of founders, exceptional expansion and contraction of the population size and a long history of marriage within the faith. In addition, the current Ashkenazi population did not originate from all of its founders, but selectively from a small fraction of wealthier people. The consequence of the unique demographic history of Ashkenazi Jews is that they have a very similar genetic makeup."

Darvasi, a senior lecturer at the Hebrew University's Life Science Institute, is an internationally recognized geneticist with numerous publications in leading scientific journals. Prior to founding IDgene, he was associate director of human genetics and head of statistical genetics at the giant British pharmaceutical company SmithKline Beecham (now the world's largest pharmaceutical company, GlaxoSmithKline), where he introduced several of the genetic strategies that are applied there today.

Genetic diseases are so-named because they are caused by a genetic defect, with each child of two parent "carriers"having a one-in-four risk for developing the disorder. Ashkenazi Jews are particularly susceptible to a number of inherited fatal disorders, such as Tay-Sachs, Gaucher disease, Canavan disease, Bloom syndrome, idiopathic torsion dystonia and familial dysautonomia, because a mutant gene in a single "founder"had been passed down through the generations.

But a multiplicity of unknown genes contributes to other diseases - such as diabetes, atherosclerosis, hypertension, cancers, Alzheimer's, Parkinson's, osteoporosis, schizophrenia and rheumatoid arthritis - that plague the human race. Scientists do not yet know which genes are responsible for these diseases and how much the influence of environmental factors such as a high-fat diet, smoking, lack of exercise, pollution and stress can either trigger or worsen these conditions in genetically susceptible people. Darvasi believes that Ashkenazi Jews, who constitute some 2.5 million people in Israel and 80 percent of world Jewry, are a genetic goldmine - the key to discovering which specific genes are involved in these disorders, and thus to targeting their root causes.

Instead of working from the gene level to discover what diseases they help cause, IDgene staffers are collecting blood samples from Ashkenazi disease sufferers. Hospitals patients who are suffering from any of the major chronic diseases and have four Ashkenazi grandparents are asked to donate a single blood sample for genetic testing (written consent is obligatory, and that the resulting data is kept completely anonymous). The company, which aims at several thousand vials, also collects blood samples from Ashkenazi Jewish patients in the US. Identifying slight variations and targeting these shared mutant genes in a homogeneous population here can tease them out of the genome, Darvasi explains.

But before they reach the ultimate aim - the customized computer design of unique and specific medications for these disorders (which may be many years into the future) - IDgene wants to optimize existing treatments, enhance accurate diagnostics and promote ways of preventing these disorders in susceptible people. Israel's highly developed Western-style medicine and well-trained researchers are also factors in promoting this research, says Darvasi.

Could life expectancy ever become "too long "if these chronic and fatal diseases are eventually defeated? "We want people not only to live longer, but to enjoy a better quality of life," Darvasi stresses. "For this, we have to work on the ageing process itself. If people age more slowly and suffer from fewer diseases, it will be a positive thing; there will be more contributing members of society and fewer who are sick and need help."