This Article Full Text (PDF) eLetters: Submit a response to this article Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services E-mail this article link to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Langreth, B. R. Articles by Waldholz, M. Search for Related Content PubMed PubMed Citation Articles by Langreth, B. R. Articles by Waldholz, M.

New Era of Personalized Medicine

Targeting Drugs For Each Unique Genetic Profile

Staff Reporters of The Wall Street Journal

THE PHARMACEUTICAL industry makes billions of dollars a year selling one-size-fits-all medicines. But now the race is on to come up with tailor-made drugs that will treat people based on their individual genetic makeup.

Drug companies hope to create a map of genetic landmarks that will become a potent new tool for uncovering the minute inborn differences that make some individuals particularly susceptible to certain diseases. With that knowledge, the drug makers hope to develop safer, more potent drugs that can more precisely target the variety of biological quirks that underlie each major disease. Their goal: a cornucopia of personalized medicines that will produce huge profits into the next century.

"One of the more important things going on right now in human biology is distinguishing the large genetic variability among individuals," says John Keller, vice president and director of the alliance and technology group at SmithKline Beecham PLC, the British-American drug company.

Already, several major drug makers, including Bristol-Myers Squibb Co., Roche Holding Ltd. and Novartis AG, are using the small number of genetic signposts currently available to them to finetune the delivery of existing drugs in an attempt to increase their effectiveness. Roche, the Swiss drug giant, is using gene markers to identify breast-cancer patients who are most likely to respond to its drug Xeloda. The drug is converted to its active form by enzymes inside the body. Roche believes that patients who don't respond to the drug may have defects or alterations in these enzymes that make it hard for them to process the medicine.

The project to map human genes involves an unprecedented alliance of 10 of the world's largest drug companies, including Roche, Novartis and Glaxo Wellcome PLC. The consortium will launch a two-year, $45 million program to identify several hundred thousand chemical signposts that will help gene hunters explore the vast regions of human DNA.

As first reported last month in The Wall Street Journal, the companies and their gene-hunting partners in university labs will use this information to assemble a catalog of the biological diversities that explain many of the physical differences among humans. The companies believe this information will help them create drugs specifically designed to target each person's unique genetic profile.

For example, consortium-member Bristol-Myers is sponsoring a research program at the Whitehead/MIT Center for Genome Research, using existing gene markers to search for genes that cause or increase the risk of heart disease, diabetes and asthma. The MIT group is sifting through hundreds of genes to identify those that are altered in people who get disease. These genes, in turn, will illuminate biochemical pathways that Bristol-Myers can target with new drugs.

Eric Lander, who directs the MIT genome center, calls the gene map "the framework for the future of medicine and biomedical science." He says the drug makers’ plan to publicly release their findings is especially valuable, because it means the findings won't be exclusively controlled by small biotech companies or even large drug makers rushing to produce their own private gene databases. One small company, Genset SA of Paris, says it has already used its preliminary gene map to identify three genes involved in prostate cancer. But so far the company has declined to identify the genes so that other cancer researchers can begin working to understand the genes’ role and develop treatments.

	How Fine-Tuning By Drug Makers Will Work

Top How Fine-Tuning By Drug...

 

• Herceptin from Genentech Inc.Breast-cancer drug developed specifically to treat a minority of patients whose tumors have elevated levels of a protein, her-2.
  
• Xeloda from Roche Holding Ltd.Some patients may respond better to this breast-cancer drug than others because of differences in enzymes that process it.
  
• Clozaril from Novartis AGOld schizophrenia drug that causes rare blood disorder in a small number of patients; researchers hope to use gene-map data to develop test to predict who will get the disorder.
  
• Orzel from Bristol-Myers Squibb Co.Colorectal cancer drug currently under FDA review; company is performing studies to identify which patients are more likely to develop diarrhea and other side-effects from the drug.
  

The mapping project is separate from the Human Genome Project sponsored by the federal government that expects to produce a complete sequence of the entire three billion subunits, or nucleotide letters, that constitute human DNA. But the sequencing project and the new mapping plan are expected to make it possible for both groups to complete their tasks more quickly.

The map will be made up of so-called SNPs (pronounced "snips"), which are minute genetic alterations sprinkled in millions of locations across human DNA. Essentially, they are places in the genetic code where DNA differs from one person to the next by a single letter. Scientists now believe these SNPs, short for single nucleotide polymorphisms, are the ever-so-slight genetic variations between human beings that predispose some people to disease and explain why some respond better to certain drugs. The new project will draw up a map of at least 150,000 SNPs distributed evenly throughout the DNA, much like mile markers along a long stretch of highway.

View larger version (29K): [in this window] [in a new window]

Companies also hope the SNPs will be the basis of simple blood tests that will tell doctors who will benefit from certain drugs and who risks developing serious side effects. Right now, even the best medicines work in only 50% to 70% of the patients who get them, and the companies hope SNP technology will raise that percentage.

Researchers at Novartis also hope to resurrect sales of its schizophrenia drug Clozaril, which is considered one of the most powerful schizophrenia drugs ever invented. Because 1.3% of patients who take it develop a serious and potentially deadly blood disorder, the drug is usually given only as a treatment of last resort, and even then patients must get weekly blood tests. The company hopes to use SNPs to identify which patients are likely to get the blood disorder. Those patients would avoid the drug, but the vast majority of other patients would no longer need the blood test.

At Roche, investigators are hoping the new map will help predict which patients are likely to get the greatest long-term benefit from its experimental Xenical obesity drug. The company also hopes to find genetic markers that will help predict which women with osteoporosis are most at risk for hip fractures. Such a finding could be the basis for a diagnostic test to identify those patients that need to be treated most aggressively.

Ultimately, says Paul Herrling of Norvartis, the map will help drug companies "move away from symptomatic treatment of disease to disease prevention, disease modification and, sometimes, cures."

[This article appeared in THE WALL STREET JOURNAL, issue of April 16, 1999.]

This article has been cited by other articles:

				K. C. Stange and W. R. Phillips In This Issue: Real Change Is Real Hard in the Real World Ann. Fam. Med, March 1, 2007; 5(2): 98 - 100. [Full Text] [PDF]

				K. C. Stange and L. S. Acheson In This Issue: Communication in the Era of 'Personalized' Medicine Ann. Fam. Med, May 1, 2006; 4(3): 194 - 196. [Full Text] [PDF]

				Annals Journal Club: A RADICAL Approach Ann. Fam. Med, May 1, 2006; 4(3): iii - iii. [Full Text] [PDF]

This Article Full Text (PDF) eLetters: Submit a response to this article Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services E-mail this article link to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Langreth, B. R. Articles by Waldholz, M. Search for Related Content PubMed PubMed Citation Articles by Langreth, B. R. Articles by Waldholz, M.