How Genetic Variation is Affecting Drug Development
In the March 2 issue of the Swiss newspaper “SonntagsZeitung” is an interesting article entitled “Pillen in Massanzug” which can be translated as “Custom-made Pills” [1]. The article basically explores how increased knowledge of human genetics is creating changes in drug development and speculates on the possibility of personalized medicine.
Here are some examples:
Carbamazepine
In December last year, The US FDA recommended genetic testing in connection with the prescription of the drug carbamazepine. Carbamazepine is commonly used for the treatment of epilepsy, bipolar disorder and neuropathic pain. Recently, certain patients – notably of Asian ancestry - were observed to develop serious skin disorders as adverse reaction to the drug. “Studies have found a strong association between certain serious skin reactions and an inherited variant of a gene, HLA-B* 1502, an immune system gene, found almost exclusively in people with Asian ancestry.” [2] Prior to this recent recommendation, genetic testing was recommended for all patients regardless of ethnicity. However, with the recent results of genetic studies, genetically high-risk patients have been narrowed down to an ethnic group, making life easier for health professionals and their patients, as well as the drug manufacturers themselves.
Statins
The use of the anti-cholesterol drugs statins has been associated with muscle pains and weakness. Researchers have recently identified the gene that may hold the key to statin-induced muscle toxicity. The atrogin-1 gene is associated with different types of muscle atrophy. In vitro and in vivo studies show that statins activate atrogin-1 gene leading to skeletal muscle damage [3]. Atrogin-1 gene expression may differ in different people, explaining the wide range of muscle symptoms (from very mild to debilitating) in statin users.
Trastuzumab
The anti-cancer drug Herceptin (trastuzumab) is a HER2/neu receptor antagonist and is indicated only for patients with HER2-overexpressing breast cancer. The drug specifically targets a gene (HER2) that causes breast cancer so that patients with other types of breast cancer cannot benefit from this drug. Considering the rather serious side effects involved (cardiomyopathy and pulmonary toxicity), HER2 gene testing is highly recommended before chemotherapy can be started. [4]
Ezetimibe
Ezetimibe is one of 2 combination drugs tested by the controversial ENHANCE trial. The study participants have heterozygous familial hypercholesterolemia, a genetic disorder characterized by cholesterol deposition and high plasma concentrations of low-density lipoprotein cholesterol [5]. Unfortunately, the trial results did not show any benefit from ezetimibe. However, drug testing on genetically distinct populations is becoming a common practice in drug development.
So how far are we from personalized medications? I personally think this will soon be technologically possible but whether it`s financially feasible is a different matter.
References:
1. SonntagsZeitung, 2 March 2008, p.73
2. FDA News, 12 December 2007.
3. Hanai et al. J Clin Invest. 2007 December 3; 117(12): 3940–3951.
4. Herceptin prescribing information, Jan 2008.
5. Yuan et al. CMAJ • April 11, 2006; 174 (8).
One Comment
- 23andMe: DNA test goes mainstream | Current Events | Babies Online The Blog replied:
[…] Research studies are pointing to the fact that a person’s genetic make up can determine not only his/her risks for certain diseases, it has also an influence on a person’s response to certain drugs and treatments. Personal DNA information is therefore very important in the so-called personalized medicine. […]
November 19th, 2008 at 12:09 pm. Permalink.