Better drugs without genetic testing?
Recently, Dr. Allen Roses, vice-president of genetics at GlaxoSmithKline (GSK), said that fewer than half of the patients prescribed drugs actually derived any benefit from them (Reuters). This raises a few issues that should be openly addressed. Why? How? and what can be done? First to the why. Dr. Roses' explanation would suggest that because of our inherent genetic variation, as many as fifty percent of us would not benefit from the clinically prescribed dosages of many drugs. This suggests that the problem could entail multiple problems that have often been overlooked or have gone previously unconsidered. Although it is the new trend to consider that one day we will all get genetic testing to determine our susceptibility, or lack thereof, to various medicines, we should all pause at this juncture and question the consequences, unintended or otherwise, of such a course. Personally, I believe that there are better methods to address this issue, which relates to the second and third questions of how and what can be done to correct it.
One of the overlooked perils of drug development is the occurrence of desensitization, which is also called tolerance, fade, tachyphylaxis or down-regulation. At one time or another, we all have experienced the gradual loss of drug effectiveness with continued use. Many in the industry believe that by selecting the proper dosage regime drug-receptor desensitization can be minimized or prevented. Rightly or wrongly, they create a tightrope that patients and doctors must walk when utilizing the proper dosages and types of medications.
This may affect anywhere from 30 to 50 percent of all pharmaceuticals and be a fertile area for drug development and improvement in the future. Given some of the disturbing reports that have shown upwards of 90,000 cases per year of reported medical errors in the US alone , the production of safer drugs should be a top priority in the pharmaceutical field. Yet why haven't the major companies done more to produce safer drugs?
A partial explanation would be that it is much more expensive to ensure safer drugs, but an alternative explanation may be that they lack the technology to understand and correct the problem. Certainly, the major companies would want the safest product on the market. This would not only make sense from a medical standpoint, but a marketing one as well. Safer drugs require that all of the variables of drug development be evaluated and adjusted for the greatest number of people using these medications. Surprisingly, the safest drugs may come from using agonist/antagonist combinations in ways to prevent, diminish or control drug-receptor desensitization. This would be analogous to creating designer partial agonists in ways that have been previously overlooked, but would offer a new technology for enhancing the safety and efficacy of many pharmaceuticals [2,3]. I believe that this approach would produce better drugs without the need for extensive genetic testing.
1 Kohn, L.T. et al., eds (2000) Institute of Medicine Report - To err is human : building a safer health system. National Academy Press, Washington, D.C.
2 Lanzara, R. (2003) Agonist/antagonist combinations at the beta-1-adrenergic receptor for preventing receptor desensitization. The Chemweb Preprint Server
3 Lanzara, R. (2003) Compositions to enhance the efficacy and safety of bio-pharmaceutical drugs. US Pat. 6,593,094
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