- Email: [email protected]
Vaccine effective in reducing genital herpes disease in women
SCIENCE AND MEDICINE
Vaccine effective in reducing genital herpes disease in women on 7550 young women. “We looked at humeral and cellular immunity and it didn’t really explain differences between people who responded and those who didn’t”, says Tyring. “In the next study, we’ll be evaluating mucosal immunity which will hopefully give us more insight.” But the biggest challenge, he adds, will be getting people to use the vaccine once it comes on the market. Although the results are somewhat encouraging, the lack of efficacy in men, and in women with prior HSV-1 infection, and the lack of a significant reduction in infection are troubling observations, comments Charles Prober (Stanford University, Palo Alto, CA, US). “Because the frequency of infection—and thus latency—was not impacted by vaccination and because most infections spread from the silent reactivation of herpes from a latently infected individual to a susceptible host, this vaccine may have no effect on the continued escalation of the silent epidemic of genital herpes.” Science Photo Library
The vaccine was 38% effective in vaccine for genital herpes could the first study, and 42% effective for become available within the next women in the second study. For both few years, report US researchers this trials, a subanalysis showed that vacweek. The results of two clinical trials cine efficacy rose to 73% and 74%, found that a glycoprotein-D subunit vaccine prevented herpes disease in more than 70% of women who Rights were not granted to were seronegative for both herpes simplex 1 and 2 (HSV-1/2). include this image in However, the vaccine does not electronic media. Please refer appear to be effective in men. “This is the first time that a vacto the printed journal. cine has prevented genital herpes, and also the first time that a vaccine has protected women and not men,” says study researcher Steve Tyring (University of Texas Medical Branch, Galveston, TX, USA). “The interesting question is why did it protect women and not A vaccine for herpes on the horizon? men.” respectively, in women who were The efficacy of the vaccine was seronegative for both HSV-1 and evaluated in 2714 subjects (978 HSV-2 (N Eng J Med 2002; 347: women) who participated in 1652–61). the multicentre, double-blind, ranWhile the vaccine was effective in domised trials. In the first study, all preventing disease, explains Tyring, participants were seronegative for it was not significant in preventing both HSV-1 and HSV-2, while in the infection, although there was a trend second study, they were of varying in that direction. HSV serologic status. All participants New studies scheduled to begin in had regular sexual partners with a January, 2003, will test the vaccine history of genital herpes infection.
A
Roxanne Nelson
New muscular dystrophy treatment tested in mice
M
yostatin blockade may provide a drug-based treatment for muscular dystrophies, say Tejvir Khurana (University of Pennsylvania School of Medicine, Philadelphia, PA, USA) and colleagues. The researchers report that treatment of the mdx mouse model of Duchenne muscular dystrophy (DMD) with antibodies that block the action of myostatin, a negative regulator of skeletal muscle growth, improves muscle function. “We believe myostatin blockade works by increasing the committment of pre-existing muscle progenitor cells to make more functional muscle”, says Khurana. “The resultant larger muscles, though they still have the dystrophin deficit, are probably able to handle the workload better. Myostatin blockade need not be used alone”, he continues. “It may also prove useful as an adjunct to direct gene therapy for the dystrophin deficit.” DMD is an X-linked musclewasting disease caused by dystrophin mutations. Lack of
1756
functional dystrophin results in progressive contraction-induced muscle injury and patients usually become wheelchair-bound by about 12 years of age. Attempts have been made to use gene therapy to correct the gene deficit in animal DMD models but, says Paula Clemens (University of Pittsburgh, PA, USA), although these experiments indicate that this approach should be feasible, gene delivery problems have generally prevented the move into clinical trials. “To date the only proven therapeutics for DMD are corticosteroids”, she explains, “although the Cooperative International Neuromuscular Research Group is currently testing several pharmaceutical agents that are designed to favourably modify the downstream effects of dystrophin deficiency”. In their pharmaceutical approach, Khurana’s team has exploited the observation that animals with myostatin mutations have increased muscle mass. The researchers treated mdx mice with myostatin-blocking antibodies each
week for 3 months. Compared to control mice, the treated mice had increased muscle mass, size, and absolute strength, and less muscle degeneration (Nature 2002; 420: 418–21). The team now plans to test myostatin blockade in other mouse muscular dystrophy models and in a dog DMD model. “This interesting strategy is very different from others currently being pursued”, notes Clemens. “But since the treatment was started at 4 weeks of age when mdx mice have a burst of muscle necrosis, the treatment may be preventive rather than curative.” Khurana agrees that his findings could be a result of something analogous to the “honeymoon” period in DMD. “It is difficult to access the benefits of a therapeutic intervention during that period”, he says, “and we don’t know when the equivalent periods are in mice so we now plan to extend our experiments to cover different time points”. Jane Bradbury
THE LANCET • Vol 360 • November 30, 2002 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet Publishing Group.
Vaccine effective in reducing genital herpes disease in women on 7550 young women. “We looked at humeral and cellular immunity and it didn’t really explain differences between people who responded and those who didn’t”, says Tyring. “In the next study, we’ll be evaluating mucosal immunity which will hopefully give us more insight.” But the biggest challenge, he adds, will be getting people to use the vaccine once it comes on the market. Although the results are somewhat encouraging, the lack of efficacy in men, and in women with prior HSV-1 infection, and the lack of a significant reduction in infection are troubling observations, comments Charles Prober (Stanford University, Palo Alto, CA, US). “Because the frequency of infection—and thus latency—was not impacted by vaccination and because most infections spread from the silent reactivation of herpes from a latently infected individual to a susceptible host, this vaccine may have no effect on the continued escalation of the silent epidemic of genital herpes.” Science Photo Library
The vaccine was 38% effective in vaccine for genital herpes could the first study, and 42% effective for become available within the next women in the second study. For both few years, report US researchers this trials, a subanalysis showed that vacweek. The results of two clinical trials cine efficacy rose to 73% and 74%, found that a glycoprotein-D subunit vaccine prevented herpes disease in more than 70% of women who Rights were not granted to were seronegative for both herpes simplex 1 and 2 (HSV-1/2). include this image in However, the vaccine does not electronic media. Please refer appear to be effective in men. “This is the first time that a vacto the printed journal. cine has prevented genital herpes, and also the first time that a vaccine has protected women and not men,” says study researcher Steve Tyring (University of Texas Medical Branch, Galveston, TX, USA). “The interesting question is why did it protect women and not A vaccine for herpes on the horizon? men.” respectively, in women who were The efficacy of the vaccine was seronegative for both HSV-1 and evaluated in 2714 subjects (978 HSV-2 (N Eng J Med 2002; 347: women) who participated in 1652–61). the multicentre, double-blind, ranWhile the vaccine was effective in domised trials. In the first study, all preventing disease, explains Tyring, participants were seronegative for it was not significant in preventing both HSV-1 and HSV-2, while in the infection, although there was a trend second study, they were of varying in that direction. HSV serologic status. All participants New studies scheduled to begin in had regular sexual partners with a January, 2003, will test the vaccine history of genital herpes infection.
A
Roxanne Nelson
New muscular dystrophy treatment tested in mice
M
yostatin blockade may provide a drug-based treatment for muscular dystrophies, say Tejvir Khurana (University of Pennsylvania School of Medicine, Philadelphia, PA, USA) and colleagues. The researchers report that treatment of the mdx mouse model of Duchenne muscular dystrophy (DMD) with antibodies that block the action of myostatin, a negative regulator of skeletal muscle growth, improves muscle function. “We believe myostatin blockade works by increasing the committment of pre-existing muscle progenitor cells to make more functional muscle”, says Khurana. “The resultant larger muscles, though they still have the dystrophin deficit, are probably able to handle the workload better. Myostatin blockade need not be used alone”, he continues. “It may also prove useful as an adjunct to direct gene therapy for the dystrophin deficit.” DMD is an X-linked musclewasting disease caused by dystrophin mutations. Lack of
1756
functional dystrophin results in progressive contraction-induced muscle injury and patients usually become wheelchair-bound by about 12 years of age. Attempts have been made to use gene therapy to correct the gene deficit in animal DMD models but, says Paula Clemens (University of Pittsburgh, PA, USA), although these experiments indicate that this approach should be feasible, gene delivery problems have generally prevented the move into clinical trials. “To date the only proven therapeutics for DMD are corticosteroids”, she explains, “although the Cooperative International Neuromuscular Research Group is currently testing several pharmaceutical agents that are designed to favourably modify the downstream effects of dystrophin deficiency”. In their pharmaceutical approach, Khurana’s team has exploited the observation that animals with myostatin mutations have increased muscle mass. The researchers treated mdx mice with myostatin-blocking antibodies each
week for 3 months. Compared to control mice, the treated mice had increased muscle mass, size, and absolute strength, and less muscle degeneration (Nature 2002; 420: 418–21). The team now plans to test myostatin blockade in other mouse muscular dystrophy models and in a dog DMD model. “This interesting strategy is very different from others currently being pursued”, notes Clemens. “But since the treatment was started at 4 weeks of age when mdx mice have a burst of muscle necrosis, the treatment may be preventive rather than curative.” Khurana agrees that his findings could be a result of something analogous to the “honeymoon” period in DMD. “It is difficult to access the benefits of a therapeutic intervention during that period”, he says, “and we don’t know when the equivalent periods are in mice so we now plan to extend our experiments to cover different time points”. Jane Bradbury
THE LANCET • Vol 360 • November 30, 2002 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet Publishing Group.