(GlaxoWellcome press release) - Great excitement has been sparked by the race to complete the sequencing of the human genome. Much has been said about the race itself, the characters involved and the politics that surround it. But this is not the end of the story - this is only the beginning.
The mammoth task of taking the sequence, finding genes and understanding how they contribute to diseases so that better medicines can be discovered is just beginning. A review supplement, published today in Nature magazine, explains how this task might be achieved. The review, written by Dr Allen Roses, World-wide Director of Genetics at Glaxo Wellcome, puts into context what the information yielded from the human genome means for identifying drug targets and turning those targets into discovery programmes for new medicines.
"There is still much work to be done to convert information from the human genome into better medicines. Once we have found a gene which predisposes individuals to a certain disease it could take 10-15 years before a medicine results" explains Dr Roses. "However the ability to use information from patients' DNA to more accurately prescribe medicines, that are more likely to be beneficial and less likely to cause serious side effects, will occur sooner than many think." He added
There are already notable successes. A gene on chromosome 19 called APOE has been shown to alter the risk of Alzheimer disease. Research is underway to understand the function of the different forms of this gene in the disease pathway. This will help find ways for medicines to stop or prevent this debilitating illness. Glaxo Wellcome has initiated research in other disease areas including, asthma, COPD, cardiovascular disease, osteoarthritis, migraine, diabetes and depression to identify genes that predispose individuals to these diseases.
Over the next few years the genetics revolution is unlikely to result in the introduction of a wave of new medicines. Where it will impact is on the provision of a whole host of new, validated, disease targets against which compounds can be designed and screened. Thus over time it will be possible to use genetic methods to begin to develop new medicines - medicines that act at the root causes of many common diseases.
In the meantime, perhaps in as little as 3-5 years, new techniques in pharmacogenetics will enable a physician to compare an individual's genetic profile to a "medicine response profile". This will allow physicians to accurately predict whether the patient is likely to benefit from a given medicine or is likely to experience serious side effects.
Dr Roses explains a concept of how it may be possible to use DNA technology to establish an enhanced drug surveillance system. In this concept, blood samples for DNA analysis are taken from patients who receive a new medicine. In the event of rare, but serious side effects the DNA samples of those that experience the side effect can be compared with samples of those that did not. This will enable differences in DNA that are associated with the side effect to be identified. Through this system DNA from subsequent patients can be used to identify those who are susceptible to the side effect before the medicine is prescribed.
The same technology can be applied to identify patients likely to benefit from a medicine. As Dr Roses explains in the review, this could be used to streamline drug development enabling effective medicines to be made available to patients more quickly. This would also accelerate the discovery of additional drug targets and the discovery of new drugs for unmet medical needs. It would become viable, for example, to develop medicines for small populations for whom existing drugs do not work.
Glaxo Wellcome is already undertaking genetic research to provide medicine response profiles for some of its marketed products and many of its products in development. The first pharmacogenetic profile is likely to be available in 3 - 5 years.
By the end of 1999, Glaxo Wellcome had included genetic research in nearly 60 clinical trials of 16 compounds in 26 countries, with thousands of samples collected from almost 1,800 clinical sites. Feedback from the investigators involved in these trials suggests they are very enthusiastic about participating in this genetic research, largely because of its importance in the development of new medicines. Feedback from the participating patients has been much the same.
"The potential impact that pharmacogenetics could have on healthcare over the next few years could be tremendous," said Dr Roses. "This offers real opportunities for patients, doctors, healthcare providers and pharmaceutical companies. Glaxo Wellcome already has a large research programme underway to produce medicine response profiles for many of its products and is continuing to drive these programs forward, but it will need all sections of the healthcare industry to get fully involved in order to turn this concept into a reality."
© 2000 Mena Report (www.menareport.com)
