The 21st century offers many exciting changes in the pharmaceutical industry, and GlaxoSmithKline (GSK) is at the forefront. GSK devotes significant resources to several major areas of genetic and genomic research that are likely to have a significant impact on patient care in the coming decade.

The results of GSK's genetic research may also help predict patients' responses to medicines so that health care providers can prescribe safer and more effective medicines for patients, resulting in better health outcomes for patients.

Technology and Cooperation Have Paved the Way

Three public efforts have accelerated genetic research: The Human Genome Project, the SNP Consortium and the International HapMap Project.

In April, 2003, fifty years after the structure of DNA was first published, the Human Genome Project made an announcement of historical proportions: It had assembled a complete physical map of the DNA sequence of the human genome — the genetic blueprint for a human being. This opens the door to a new and even more challenging era devoted to understanding DNA’s functional significance and organization (NIH Press Release).

Genetic Blueprint

British Prime Minister Tony Blair called the genome project "the first great technological triumph of the 21st century”. Former U.S. President Bill Clinton said, "Humankind is on the verge of gaining immense new power to heal. Genome science will revolutionize the diagnosis, prevention and treatment of most, if not all, human diseases."

The Human Genome Project has fundamentally changed the way we think about disease diagnosis and treatment, drug development, and our personal medical histories. It is expected to revolutionize the practice of medicine by paving the way for new drugs and medical therapies.

Another impressive effort by the SNP Consortium, which includes several pharmaceutical (including GSK), information and technology companies, academic centers, and a charitable trust, has resulted in the mapping of more than 1.8 million human SNPs. The maps, which are still being updated and refined, now are publicly available to researchers across the world.
Scientists believe that the SNP maps will help them identify the multiple genes associated with complex diseases such as cancer, diabetes, and heart disease.

A third effort is the International HapMap Project, a partnership of scientists and funding agencies from Canada, China, Japan, Nigeria, the United Kingdom and the United States formed to develop a public resource that will help researchers find genes associated with human disease and response to pharmaceuticals.

The goal of the International HapMap Project is to develop a haplotype map of the human genome, which will describe the common patterns of human DNA sequence variation. The HapMap is expected to be a key resource as it will include the chromosome regions with sets of strongly associated SNPs, and the haplotypes in those regions.

The availability of data from the Human Genome Project, and SNP and haplotype maps enable researchers to accomplish tasks in weeks or months that once took years or decades. Scientists can work faster, do more, and do it more cost-effectively than ever before.

Researchers trying to discover the genes that affect a disease, such as diabetes, will compare a group of people with the disease to a group of people without the disease. Once researchers find the genes or molecules involved in diseases, they can work on developing medicines that target those molecules and treat the cause of the disease, not just its symptoms.

Discovering New Targets

GSK genomic scientists use different strategies to identify promising new targets for medicines:

• They look for genes whose function is known and whose specific proteins potentially can be affected by chemical compounds.

• They compare the sequences (order of DNA bases) of newly identified genes with those of genes whose functions are already known, and make educated guesses about which genes might be related to specific biochemical pathways in the body and how they might affect the occurrence or treatment of disease.

• They identify genes that vary between healthy people and those who have a specific disease. When a genetic difference is discovered, scientists can use genomic tools to discover the function of the disease-linked gene or genes. The protein produced by the gene may not be a suitable target itself, but may point scientists in the right direction of finding related proteins and genes that are good targets.

• They discover the function of genes that are associated with a disease. For example, a disease-associated gene variant may code for a specific enzyme. Once the role of the enzyme has been identified and its relationship to the disease is understood, it might provide a target for a new medicine.

Selecting the Most Promising New Medicines

Scientists use genomic screening techniques early in the drug development process in an effort to help identify compounds that are likely to cause serious side effects in a significant number of people. One example involves screening potential drugs for the pathways that are likely to be used in their metabolism. Many of these pathways are known to be affected by genetic variants, and people with these variants may not respond well to standard doses of drugs that are broken down by them. By eliminating compounds likely to cause problems early in the process, human risk will be decreased and efficiency will be increased."

Identifying Biomarkers

Scientists use genomic techniques to identify genetic markers that are linked to diseases or responses to medicines. These markers can be used to narrow the search for genes that cause specific changes in the body or may have the potential to identify people likely to develop a disease or respond to a medicine in a certain way.

GSK's genomic scientists use and develop many cutting edge technologies to support these efforts. They identify and study proteins and the interactions among them; create animal models to help understand the genetic and biochemical basis of disease; and study the genetic mechanisms that control what proteins are expressed, when, where and how. This challenging and complex scientific work may eventually lead to the more efficient development of safer and better medicines.