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Enteroviruses succumb to new drug
Enteroviruses succumb to new drug
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nteroviruses cause 10–15 million symptomatic infections per year in the USA, and are the leading cause of aseptic meningitis, reported Harley Rotbart (University of Colorado, Denver, CO, USA) at the 39th Interscience Conference on Antimicrobial Agents and Chemotherapy (San Francisco, CA, USA; Sept 26–29). However, data from several trials on the treatment of enteroviral infections with the antiviral pleconaril look promising. Pleconaril, which acts by blocking the viral uncoating process (and thus blocking release of viral RNA), has now been tested in more than 1700 patients. The drug is orally bioavailable and has good centralnervous-system and nasal penetration. S D Shafran (University of Alberta, Edmonton, Canada) reported a randomised placebocontrolled trial of pleconaril in
patients aged 14–65 years with confirmed enteroviral meningitis. Compared with those treated with placebo, pleconaril-treated patients had a significant 2-day reduction in time to resolution of headache and symptoms of meningitis, and in time taken to return to work. In a randomised trial in adults with acute respiratory illness, described by Frederick Hayden (University of Virginia, Charlottesville, VA, USA), time to resolution of symptoms was more than 3 days shorter in patients treated with pleconaril than in those given placebo. And Rotbart described pleconaril use on a compassionate basis in 70 children with life-threatening enteroviral infections; 29 of 38 with adequate data had clinical improvement. As yet, there is no clinical evidence of resistance to pleconaril. John McConnell
Mutant telomerase halts cancer-cell growth when expressed alongside normal telomerase in human cancer-cell lines, results in complete inhibition of all telomerase activity, a decrease in telomere length, and death of the tumour cells. The cells expressing mutant hTERT are no longer tumorigenic in nude mice. The researchers say that “specific, potent inhibitors of the hTERT enzyme are likely to be very effective in limiting the growth of many types of human cancer cells” (Nat Med 1999; 5: 1164–70). Weinberg and colleagues note that strategies to inactivate the RNA subunit of telomerase have not consistently led to complete New inhibitors to call a halt to cell division? inhibition of telomerase activity, whereas their own results “demonIn normal cells, which do not strate that complete inhibition of express telomerase, telomeric DNA telomerase can be achieved by target(located at the ends of chromosomes) ing the active site of hTERT”. is progressively lost at successive cell Unlike most chemotherapeutic divisions. When the telomeres shorten agents, telomerase inhibitors might to a critical length, cell proliferation not induce cytotoxicity immediately, ceases. In cancer cells, telomerase because the telomeres must first reach stimulates de-novo synthesis of a critically short length. “This lag”, say telomeric DNA. Thus telomeres do the researchers, “may allow clinically not shorten, and cell proliferation important tumour-cell growth”. For continues unchecked. this reason, treatment would probably Robert Weinberg (Whitehead need to be combined with prior Institute for Biomedical Research, debulking of the tumour mass. Cambridge, MA, USA) and colleagues have created a mutant, catalytically inactive form of hTERT, which, Dorothy Bonn
nhibition of the catalytic subunit of telomerase (human telomerase reverse transcriptase, hTERT) could be important in the development of antineoplastic therapies, say US researchers.
I
THE LANCET • Vol 354 • October 2, 1999
UK experts report on safety of CS spray UK report released on Sept 23 concludes that the “available data, did not, in general, raise concerns regarding the health effects of CS spray itself”. But, it notes, “no comprehensive investigation of the effects of CS spray in humans was available, nor has there been any systematic follow-up of individuals who have been sprayed with CS spray”. CS spray has been used by police forces in England and Wales since March, 1996, but there have been well-publicised cases over the years of deleterious effects associated with the use of CS gas in those sprayed with the gas and police officers handling it (see Lancet 1998; 352: 159). On Sept 24, 1998, the UK Department of Health announced that the independent Committees on Toxicity, Mutagenesis and Carcinogenicity of Chemicals in Food, Consumer Products and the Environment would consider the safety of CS spray, a 5% (weight/volume) solution of 2-chlorobenzylidene malononitril in methyl isobutyl ketone. The report (see www.doh.gov. uk/cot/csgas.htm) details what is known about the effects of the two components of CS spray on cells in vitro, and on animals and people, but notes the sparsity of data on the combination of the two chemicals. So, for example, it notes that the only experimental data specifically on the combination showed that severe irritant effects on rabbit eyes had cleared by 8 days. The Committee notes that exposure of people with asthma, hypertension, or cardiovascular disease to the spray was of particular concern and that it “was not possible . . . to comment on whether individuals being treated with neuroleptic drugs are more likely to be sensitive to the effects of CS spray”. Adherence to operational guidelines for the use of CS spray is very important, it said, because it is unlikely that at the time of exposure the medical status of those exposed would be known. The report ends with the recommendation that more information needs to be obtained on the effects of CS spray on people but that “systematic studies in volunteers . . . may present insurmountable difficulties”. Instead, follow-up studies should be done on people exposed to CS spray to find out about delayed effects.
A
Jane Bradbury
1185
E
nteroviruses cause 10–15 million symptomatic infections per year in the USA, and are the leading cause of aseptic meningitis, reported Harley Rotbart (University of Colorado, Denver, CO, USA) at the 39th Interscience Conference on Antimicrobial Agents and Chemotherapy (San Francisco, CA, USA; Sept 26–29). However, data from several trials on the treatment of enteroviral infections with the antiviral pleconaril look promising. Pleconaril, which acts by blocking the viral uncoating process (and thus blocking release of viral RNA), has now been tested in more than 1700 patients. The drug is orally bioavailable and has good centralnervous-system and nasal penetration. S D Shafran (University of Alberta, Edmonton, Canada) reported a randomised placebocontrolled trial of pleconaril in
patients aged 14–65 years with confirmed enteroviral meningitis. Compared with those treated with placebo, pleconaril-treated patients had a significant 2-day reduction in time to resolution of headache and symptoms of meningitis, and in time taken to return to work. In a randomised trial in adults with acute respiratory illness, described by Frederick Hayden (University of Virginia, Charlottesville, VA, USA), time to resolution of symptoms was more than 3 days shorter in patients treated with pleconaril than in those given placebo. And Rotbart described pleconaril use on a compassionate basis in 70 children with life-threatening enteroviral infections; 29 of 38 with adequate data had clinical improvement. As yet, there is no clinical evidence of resistance to pleconaril. John McConnell
Mutant telomerase halts cancer-cell growth when expressed alongside normal telomerase in human cancer-cell lines, results in complete inhibition of all telomerase activity, a decrease in telomere length, and death of the tumour cells. The cells expressing mutant hTERT are no longer tumorigenic in nude mice. The researchers say that “specific, potent inhibitors of the hTERT enzyme are likely to be very effective in limiting the growth of many types of human cancer cells” (Nat Med 1999; 5: 1164–70). Weinberg and colleagues note that strategies to inactivate the RNA subunit of telomerase have not consistently led to complete New inhibitors to call a halt to cell division? inhibition of telomerase activity, whereas their own results “demonIn normal cells, which do not strate that complete inhibition of express telomerase, telomeric DNA telomerase can be achieved by target(located at the ends of chromosomes) ing the active site of hTERT”. is progressively lost at successive cell Unlike most chemotherapeutic divisions. When the telomeres shorten agents, telomerase inhibitors might to a critical length, cell proliferation not induce cytotoxicity immediately, ceases. In cancer cells, telomerase because the telomeres must first reach stimulates de-novo synthesis of a critically short length. “This lag”, say telomeric DNA. Thus telomeres do the researchers, “may allow clinically not shorten, and cell proliferation important tumour-cell growth”. For continues unchecked. this reason, treatment would probably Robert Weinberg (Whitehead need to be combined with prior Institute for Biomedical Research, debulking of the tumour mass. Cambridge, MA, USA) and colleagues have created a mutant, catalytically inactive form of hTERT, which, Dorothy Bonn
nhibition of the catalytic subunit of telomerase (human telomerase reverse transcriptase, hTERT) could be important in the development of antineoplastic therapies, say US researchers.
I
THE LANCET • Vol 354 • October 2, 1999
UK experts report on safety of CS spray UK report released on Sept 23 concludes that the “available data, did not, in general, raise concerns regarding the health effects of CS spray itself”. But, it notes, “no comprehensive investigation of the effects of CS spray in humans was available, nor has there been any systematic follow-up of individuals who have been sprayed with CS spray”. CS spray has been used by police forces in England and Wales since March, 1996, but there have been well-publicised cases over the years of deleterious effects associated with the use of CS gas in those sprayed with the gas and police officers handling it (see Lancet 1998; 352: 159). On Sept 24, 1998, the UK Department of Health announced that the independent Committees on Toxicity, Mutagenesis and Carcinogenicity of Chemicals in Food, Consumer Products and the Environment would consider the safety of CS spray, a 5% (weight/volume) solution of 2-chlorobenzylidene malononitril in methyl isobutyl ketone. The report (see www.doh.gov. uk/cot/csgas.htm) details what is known about the effects of the two components of CS spray on cells in vitro, and on animals and people, but notes the sparsity of data on the combination of the two chemicals. So, for example, it notes that the only experimental data specifically on the combination showed that severe irritant effects on rabbit eyes had cleared by 8 days. The Committee notes that exposure of people with asthma, hypertension, or cardiovascular disease to the spray was of particular concern and that it “was not possible . . . to comment on whether individuals being treated with neuroleptic drugs are more likely to be sensitive to the effects of CS spray”. Adherence to operational guidelines for the use of CS spray is very important, it said, because it is unlikely that at the time of exposure the medical status of those exposed would be known. The report ends with the recommendation that more information needs to be obtained on the effects of CS spray on people but that “systematic studies in volunteers . . . may present insurmountable difficulties”. Instead, follow-up studies should be done on people exposed to CS spray to find out about delayed effects.
A
Jane Bradbury
1185