Revolution Revealing Role for Sex-Specific Medicines
by Sophia Cariati
(Washington DC, 9/5/02): Women with narcolepsy, a disorder characterized by
excessive and overwhelming daytime sleepiness, respond differently than men
to treatment with the drug modafinil. This difference may be due to a sex-specific
variation in one gene, according to results of a recent study. This finding
adds to a growing body of evidence suggesting that so-called genetic polymorphisms
-- tiny snippets of DNA that differ from one person to another-- may vary not
only by race and ethnicity, but by sex too.
Since minute genetic differences can lead to big variations in an individual's
response to medication, this and related studies suggest the days of sex-tailored
medicines -- that is to say pink and blue pills, for example-- may not be too
far off. Pharmacogenomics is the burgeoning field of medicine examining the
interactions between genes and drugs. Information gathered from this discipline
promises to shape treatment plans to a patient's genetic profile, defined by
the more than 30,000 genes contained in the cells of their body. The hope is
that genetic screening can spot people most likely to respond to a particular
medication while at the same time flag those at high risk of adverse drug reactions,
which kill more than 100,000 Americans every year.
"The field of pharmacogenomics has blossomed in part because of an increased
awareness that not everyone benefits or suffers side effects to the same extent
from one drug," says Sherry Marts, PhD, scientific director of the Society
for Women's Health Research. "This study suggests that a person's sex influences
their probability of having a specific form of a gene, which can affect their
response to certain medications."
Narcolepsy is a disabling disorder affecting approximately 100,000 people in
the United States. Last year, Mehdi Tafti, PhD and colleagues at the Université
de Genève in Switzerland found evidence implicating a gene called COMT in the
severity of narcolepsy symptoms. COMT codes for an enzyme involved in processing
a brain chemical called dopamine. The drug modafinil is thought to acting upon
dopamine to alleviate narcoleptics' irresistible urge to sleep.
The researchers also reported that men and women tend to have different variations
of COMT. The COMT gene has two forms: "L" which stands for low enzyme
activity and "H" which represents high activity. Women in their study
were more apt to have two copies of the L form of the gene whereas men tend
to have the H form. In addition, the researchers found evidence to suggest that
the drug modafinil works more efficiently at relieving symptoms of narcolepsy
when the COMT enzyme is less active.
In their most recent work, the same group of researchers analyzed how 84 patients
with narcolepsy responded to modafinil and how this related to the particular
type of COMT gene they inherited. Once again, the researchers found that women
were more likely to have the L form of the gene compared with men. In addition,
the optimal dose of modafinil was an average of 100 mg lower among women compared
with men. What's more, all patients with the L form of COMT needed a lower dose
of modafinil to effectively control symptoms, confirming previous findings.
"The differences in daily dose between gender and COMT genotypes may help
individualization of modafinil treatment and highlight the importance of understanding
the genetic basis of variability in drug response," write the researchers
in their report published in The Pharmacogenomics Journal.
The Society for Women's Health Research is the nation's
only not-for-profit organization whose sole mission is to improve the health
of women through research. Founded in 1990, the Society brought to national
attention the need for the appropriate inclusion of women in major medical research
studies and the resulting need for more information about conditions affecting
women. The Society advocates increased funding for research on women's health,
encourages the study of sex differences that may affect the prevention, diagnosis
and treatment of disease, and promotes the inclusion of women in medical research
studies. Dr. Donnica Moore has been a member of the Society since 1990 and is
a past member of its Board of Directors.
For more information on clinical research, click here.
Created: 9/5/2002  - Donnica Moore, M.D.
Reviewed: 9/6/2002  - Donnica Moore, M.D.