By David N. Leff
Editor¿s note: Science Scan is a roundup of recently published biotechnology-related research.
Years ago, the French parliament was debating the question of whether women in the work force should receive equal pay with men. One delegate on the negative side of this issue stood up to remind the lawgivers, ¿After all, there is a certain difference between men and women.¿
In response to the remark, the chamber erupted with cries of ¿Vive la diffirence!¿
A compelling question now confronting physicians and researchers is why women suffer disproportionately from autoimmune diseases, notably multiple sclerosis (MS), rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE).
Autoimmune diseases affect more than 8.5 million victims in the U.S. alone, of whom 6.7 million ¿ nearly 80 percent ¿ are women. MS shows up earlier in women, but tends to progress more swiftly and harshly in men.
Now, the National Multiple Sclerosis Society in New York is urging the scientific research community at large to take on the question. The society¿s director of biomedical research programs, biochemist Patricia O¿Looney, told BioWorld Today: ¿What we did was convene a task force to look at the gender differences between all autoimmune diseases, particularly MS.¿ The group spent about 18 months assessing what is known about these diseases, and proposed an aggressive research agenda aimed at understanding why men and women respond differently to them.
The 15-member ¿Task Force on Gender, MS and Autoimmunity¿ presented its 8,000-word report last month in Science, dated Feb. 26, 1999, in an article titled ¿Sex differences in autoimmune diseases: focus on multiple sclerosis.¿
The paper made the point that the ¿reasons for the sex bias in MS and other autoimmune diseases are unclear, but may include such factors as sex-related differences in immune responsiveness, response to infection, sex-steroid effects and sex-linked genetic factors.¿ While noting that MS, RA and SLE ¿are different diseases, and probably differ in etiology, their common link is the overwhelming prevalence of these diseases in women,¿ the paper said.
Suspected causative factors in MS that the task force examined in molecular detail ranged from pregnancy to oral contraceptives to seasonal viral infection to menstruation to inheritance patterns.
O¿Looney cited the problem that ¿few people [are] doing studies looking at differences between the sexes regarding these diseases, whether in humans or animals.¿ The society¿s primary goal, she added, ¿is to increase researchers¿ awareness of these differences in designing new clinical trials or new drugs. People interested in funding for such studies can contact me at the MS Society, or Dr. Elaine Collier, chief of autoimmune diseases at NIAID [National Institute of Allergy and Infectious Diseases].¿
Two years ago. O¿Looney recalled, ¿Congress mandated the National Institutes of Health, when funding clinical trials, to include both sexes, unless there¿s a legitimate reason why women [should not be] included. For years,¿ she continued, ¿clinical trials enrolled men only for the reason that women get pregnant, etc. But then you make the conclusion in those trials that what¿s right for men is also right for women.¿
First Mouse HBV Mimic¿ Responded To Drugs That Transiently Abolished Viremia Load
More than half the world¿s population ¿ 3.5 billion people ¿ is infected with hepatitis B virus (HBV), according to the World Health Organization. In the U.S. alone, the number of cases amounts to 1.5 million. Five to 10 percent of the adult patients will contract chronic hepatitis, which can go on to cirrhosis of the liver and carcinoma. Despite this serious health threat, there are few drugs available to treat, much less prevent, the disease.
One crucial reason is the lack of a practical animal model for testing candidate vaccines and therapeutic drugs. Chimpanzees contract HBV infection, but their cost, size and life span rule them out for practical purposes. Numbers of new and promising therapeutics are stalled in the drug-development pipeline, awaiting a suitable small-animal HBV surrogate.
Now, help is at hand. It¿s heralded by a paper in the February issue of the journal Hepatology titled ¿The hepatitis B virus-Trimera mouse: A model for human HBV infection and evaluation of anti-HBV therapeutic agents.¿ Nine of its 17 co-authors are scientists at XTL Biopharmaceuticals Ltd., in Rehovot, Israel.
XTL¿s Trimera mouse gets its name from the firm¿s proprietary process that combines tissues from three genetic sources to turn a normal rodent into ¿the first mouse model that mimics human HBV.¿ First, lethal whole-body irradiation knocked out the animals¿ innate immune system. Second, bone marrow from an immune-deficient SCID mouse endowed them with a new blood-building system. Third, the now-conditioned mice accepted human HBV-infected liver fragments transplanted under their kidney capsules or in their ear flaps. The xenografts ¿took¿ in 85 percent of the recipient rodents.
Subsequent treatment with a polyclonal human HBV antibody vaccine and two antiviral reverse transcriptase inhibitors effectively reduced the percentage of infected animals and the viral load in their blood sera. When treatment stopped, viral replication promptly rebounded.
Schlomo Dagan, XTL¿s vice president, research and development, and a co-author of the paper, observed: ¿This research shows that the model is a powerful tool that can be used to predict the effects of potential antiviral therapeutic agents in development. The statistical robustness of this model is particularly valuable for diseases like HBV, where dramatic shifts in viral load during disease progression often compromise the value of preclinical studies.¿ n