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Synthetic peptide may add to efficacy of HIV-1 treatment
SCIENCE AND MEDICINE
NEWS Myoblast transplants challenged in muscular dystrophy In myoblast transplantation therapy missing or non-functional dystrophin in the muscles of patients with muscular dystrophy is replaced by injecting muscle cells from an unrelated donor into the patient. According to the technique’s proponents, these wild-type cells fuse with the patient’s muscle cells and supply functional dystrophin. By staining biopsy material with antibody specific for dystrophin, the treated muscle can be tested for expression of functional, donor-derived protein. However, patients can express some endogenous, albeit mutant Other approaches on the way? dystrophin, in their muscles, and Research continues into gene therapy for this might be mistaken for donor muscular dystrophy. At the American dystrophin if biopsy samples are Society of Genetics meeting (Oct 27–31; stained with only one antibody. Denver, CO, MI,USA), Giovanni Salvatori Concerned that the dystrophin and co-workers (University of Michigan, that has been found in patients Ann Arbor, USA) reported that by using a who have had myoblast transmodified adenovirus containing the fullplantation therapy was in fact sized dystrophin gene, stable dystrophin endogenous mutant protein, production could be induced for at least 4 Terry Partridge (MRC Clinical months in the muscles of mice with Sciences Centre, London, UK) normal immune systems. Previously, an and colleagues obtained biopsy immune response to the vector has been samples from a patient who had problematic. “Removing a reporter gene had the treatment and stained his called LacZ . . . was the key to reducing cells with multiple antibodies for the vector’s strong immunogenic effect”, dystrophin. 10–15% of the musexplains Salvatori. “We should see the cle fibres stained positively with first clinical trial of the gutted adenovirus an antibody specific for peptides in the next year or so”, adds Kay Davies encoded by exons 57–60 of the (Oxford University, UK). dystrophin gene. Antibody staining was similarly positive for all
he investigation of myoblast transplantation therapy, a treatment for muscular dystrophy being tested by the Cell Therapy Research Foundation (CTRF; Memphis, TN, USA), was designated a US FDA “Fast Track development program” on Oct 16 and phase III clinical trials are planned. But new results throw doubt on to the technique. UK and US scientists say they can find no evidence for donor-derived dystrophin in a boy who received CTRF’s treatment. The new data, they say, challenge the validity of the therapy.
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other dystrophin regions tested, except those encoded by exons 27–28 and 40–41. These antibodies did not stain the patient’s cells at all, but did stain normal muscle cells from an unrelated control. There was no difference in amounts of dystrophin in the myoblast-injected muscle and a sham-injected muscle in the same patient. The authors conclude that the dystrophin detected in the patient’s biopsy must be his own mutant protein, not protein expressed from the grafted myoblasts (Nat Med 1998; 4: 1208–09). About 120 children have been treated by CTRF at a cost of about US$150 000 per child, but there are many critics who argue that clinical trials are premature. “A lot of scientists have done myoblast trials and all have been resoundingly negative, except for the CTRF trials”, says Eric Hoffman (University of Pittsburgh, PA, USA), one of the authors of the Nature Medicine letter. “I think it would be sensible to go through all the [treated] children where dystrophin is found and see whose it is”, adds Partridge. CTRF filed a lawsuit against Hoffman and Partridge earlier this year, claiming that CTRF had been injured by intentionally defamatory statements made by the scientists. Hannah Wunsch
Synthetic peptide may add to efficacy of HIV-1 treatment
T
here is mixed news about HIV this week. The bad news that highly active antiretroviral therapy (HAART) may have to be taken for life is strengthened by two studies, despite hopes that drug reductions might be possible after suppression of viral replication (N Engl J Med 1998; 339: 1261–68, 1269–76). On a more positive note are the results of a phase I study of T-20, a synthetic peptide that blocks viral cell entry. The use of drugs with targets other than HIV-1 reverse transcriptase (RT) and protease may improve HAART efficacy.
THE LANCET • Vol 352 • November 7, 1998
J Michael Kilby (University of Alabama, Birmingham, AL, USA) and a US team treated 16 patients infected with HIV-1 with one of four doses of intravenous T-20 for 2 weeks. There were no serious adverse effects, and T-20 treatment resulted in a dose-related reduction in plasma HIV-1 RNA. In the four patients given the highest T-20 dose, viral load fell to less than 500 copies per mL. “The efficacy of T-20 in blocking de novo virus infection is comparable to that of protease and RT inhibitors”, write the authors. Subcutaneous T-20
infusions as part of a “rescue regimen” are now being investigated (Nat Med 1998; 4: 1302–07). This good news is tempered by revised 1998 population figures and projections released on Oct 28 by the United Nations. These figures highlight the increasing disparity in global availability of treatments for HIV-1 infection. In Botswana, for example, where one in four adults is infected with HIV-1, life expectancy is expected to fall from 61 years in 1990 to 41 years by 2000–2005. Kelly Morris
1527
NEWS Myoblast transplants challenged in muscular dystrophy In myoblast transplantation therapy missing or non-functional dystrophin in the muscles of patients with muscular dystrophy is replaced by injecting muscle cells from an unrelated donor into the patient. According to the technique’s proponents, these wild-type cells fuse with the patient’s muscle cells and supply functional dystrophin. By staining biopsy material with antibody specific for dystrophin, the treated muscle can be tested for expression of functional, donor-derived protein. However, patients can express some endogenous, albeit mutant Other approaches on the way? dystrophin, in their muscles, and Research continues into gene therapy for this might be mistaken for donor muscular dystrophy. At the American dystrophin if biopsy samples are Society of Genetics meeting (Oct 27–31; stained with only one antibody. Denver, CO, MI,USA), Giovanni Salvatori Concerned that the dystrophin and co-workers (University of Michigan, that has been found in patients Ann Arbor, USA) reported that by using a who have had myoblast transmodified adenovirus containing the fullplantation therapy was in fact sized dystrophin gene, stable dystrophin endogenous mutant protein, production could be induced for at least 4 Terry Partridge (MRC Clinical months in the muscles of mice with Sciences Centre, London, UK) normal immune systems. Previously, an and colleagues obtained biopsy immune response to the vector has been samples from a patient who had problematic. “Removing a reporter gene had the treatment and stained his called LacZ . . . was the key to reducing cells with multiple antibodies for the vector’s strong immunogenic effect”, dystrophin. 10–15% of the musexplains Salvatori. “We should see the cle fibres stained positively with first clinical trial of the gutted adenovirus an antibody specific for peptides in the next year or so”, adds Kay Davies encoded by exons 57–60 of the (Oxford University, UK). dystrophin gene. Antibody staining was similarly positive for all
he investigation of myoblast transplantation therapy, a treatment for muscular dystrophy being tested by the Cell Therapy Research Foundation (CTRF; Memphis, TN, USA), was designated a US FDA “Fast Track development program” on Oct 16 and phase III clinical trials are planned. But new results throw doubt on to the technique. UK and US scientists say they can find no evidence for donor-derived dystrophin in a boy who received CTRF’s treatment. The new data, they say, challenge the validity of the therapy.
T
other dystrophin regions tested, except those encoded by exons 27–28 and 40–41. These antibodies did not stain the patient’s cells at all, but did stain normal muscle cells from an unrelated control. There was no difference in amounts of dystrophin in the myoblast-injected muscle and a sham-injected muscle in the same patient. The authors conclude that the dystrophin detected in the patient’s biopsy must be his own mutant protein, not protein expressed from the grafted myoblasts (Nat Med 1998; 4: 1208–09). About 120 children have been treated by CTRF at a cost of about US$150 000 per child, but there are many critics who argue that clinical trials are premature. “A lot of scientists have done myoblast trials and all have been resoundingly negative, except for the CTRF trials”, says Eric Hoffman (University of Pittsburgh, PA, USA), one of the authors of the Nature Medicine letter. “I think it would be sensible to go through all the [treated] children where dystrophin is found and see whose it is”, adds Partridge. CTRF filed a lawsuit against Hoffman and Partridge earlier this year, claiming that CTRF had been injured by intentionally defamatory statements made by the scientists. Hannah Wunsch
Synthetic peptide may add to efficacy of HIV-1 treatment
T
here is mixed news about HIV this week. The bad news that highly active antiretroviral therapy (HAART) may have to be taken for life is strengthened by two studies, despite hopes that drug reductions might be possible after suppression of viral replication (N Engl J Med 1998; 339: 1261–68, 1269–76). On a more positive note are the results of a phase I study of T-20, a synthetic peptide that blocks viral cell entry. The use of drugs with targets other than HIV-1 reverse transcriptase (RT) and protease may improve HAART efficacy.
THE LANCET • Vol 352 • November 7, 1998
J Michael Kilby (University of Alabama, Birmingham, AL, USA) and a US team treated 16 patients infected with HIV-1 with one of four doses of intravenous T-20 for 2 weeks. There were no serious adverse effects, and T-20 treatment resulted in a dose-related reduction in plasma HIV-1 RNA. In the four patients given the highest T-20 dose, viral load fell to less than 500 copies per mL. “The efficacy of T-20 in blocking de novo virus infection is comparable to that of protease and RT inhibitors”, write the authors. Subcutaneous T-20
infusions as part of a “rescue regimen” are now being investigated (Nat Med 1998; 4: 1302–07). This good news is tempered by revised 1998 population figures and projections released on Oct 28 by the United Nations. These figures highlight the increasing disparity in global availability of treatments for HIV-1 infection. In Botswana, for example, where one in four adults is infected with HIV-1, life expectancy is expected to fall from 61 years in 1990 to 41 years by 2000–2005. Kelly Morris
1527