22 February 2011
Israeli scientists have developed compounds that could be better treatments for genetic diseases than current drugs.
Timor Baasov and his colleagues at the Israel Institute of Technology have improved compounds used to suppress faults in genes called nonsense mutations.
Nonsense mutations, which cause more than 1800 human diseases, are alterations in the genetic code that stop protein production prematurely, leading to truncated or nonfunctional proteins. Gene therapy is one treatment, but it's had limited success. With suppression therapy, small molecules allow cells' protein producing equipment to skip over nonsense mutations to restore the proteins. Aminoglycosides - antibiotic amine-modified sugars - are the only clinically available drug family known to be effective in suppression therapy, but at effective doses, the compounds have high human toxicity.
To reduce the toxicity, the team introduced a methyl group onto two aminoglycosides. They tested the new derivatives in an in vitro suppression test on six different nonsense mutations for different diseases and carried out toxicity tests on human cells. They found that the compounds exhibited significantly improved activity and reduced toxicity compared to gentamicin, an aminoglycoside antibiotic used to treat bacterial infections.
'Treating genetic disorders is one of the biggest challenges of modern medicine. The likelihood that suppression therapy could be used clinically is very feasible,' says Baasov.
'The data emphasise the enormous potential of modified aminoglycosides for [nonsense suppression] therapy to combat nonsense mutation-based disorders with limited or no current therapeutic options,' says Uwe Wolfrum, a cell biologist at the Johannes Gutenberg University of Mainz, Germany. 'This raises hope for future clinical trials.'
'Our lead compounds are under intensive examination on numerous genetic disease models including cystic fibrosis, Hurler syndrome, Rett syndrome and Usher syndrome,' concludes Baasov.
Amaya Camara-Campos
Source: RSC
Note: To read original post click on the title of the post.
Thursday, February 24, 2011
Friday, February 18, 2011
Licence rules hinder work on rare disease
Animal model off-limits to Rett-syndrome researchers.
Stashed away somewhere in a freezer in Cambridge, Massachusetts, is a mouse embryo that Etienne Joly would dearly like to get his hands on.
Joly is an immunologist based in Toulouse, France, with a keen interest in Rett syndrome, an incurable and debilitating disease that almost exclusively affects young girls. The mouse, developed by a team at the Novartis Institutes for Biomedical Research in Cambridge, carries a fluorescently tagged version of the gene that is mutated in the disease. It is the perfect tool, Joly says, for testing an idea he has about Rett syndrome. But a thicket of legal restrictions puts the mouse off-limits to anyone outside Novartis, even though scientists at the company are no longer using the model in their work on Rett syndrome.
"All scientists and families are asking for is the right to look into this disease and to try to understand it better," says Joly, who has embarked on a letter-writing campaign against the restrictions. "And when you know that there is a tool, but you can't use it because some lawyer says that you can't have the materials, then you get angry." Scientists and experts in intellectual-property issues say that the case shows how science can be impeded when onerous licensing rules govern the sharing of research materials.
Girls with Rett syndrome are healthy as babies, then progressively lose the ability to speak, move, eat and breathe normally. Because the disease is rare, affecting just one in 10,000 to 20,000 girls, it is an unattractive target for drug companies. Academic researchers have picked up the slack, and the field has moved at breakneck speed in recent years, from the 1999 discovery that defects in the gene MECP2 cause the disease, to clinical trials of possible treatments today.
Yet no one knows how the mutation causes the disease. A few years ago, Joly, who works at the Institute of Pharmacology and Structural Biology, came up with what he calls a "slightly unconventional" idea that the Rett-syndrome gene might have a role in regulating immune responses in the central nervous system. To explore his hypothesis, Joly needed an animal model that would allow him to trace where the gene is expressed.
In 2008, Joly learned about the engineered mouse. Led by molecular biologist Cecile Blaustein, the Novartis team had joined a copy of the mouse Mecp2 gene to a copy of the gene that makes enhanced green fluorescent protein (EGFP) to produce an animal in which the gene's activity can be traced throughout the brain and body (R. S. Schmid et al. Neuroreport 19, 393–398; 2008).
But after three years of trying, neither Joly nor any other Rett-syndrome researcher has been able to gain access to the mouse. When researchers asked to share it, Blaustein and her colleagues said that they would have liked to but couldn't because of the terms of Novartis's licence on EGFP, which it obtained from GE Healthcare.
Novartis and GE have been unable to negotiate a way to share the mice, says Jeff Lockwood, spokesman for the Novartis Institutes for Biomedical Research — even though Novartis has ended its research project on the mice.
When Monica Coenraads, executive director of the Rett Syndrome Research Trust in Trumbull, Connecticut, tried to broker an agreement to share the mice, GE and Novartis asked the US National Institutes of Health (NIH) in Bethesda, Maryland, to distribute the mice through its Mutant Mouse Regional Resource Centers. But Lili Portilla, senior adviser for technology transfer at the NIH National Center for Research Resources, which funds the resource centre, says that GE placed such burdensome terms on the sharing that the NIH eventually gave up. For instance, researchers would not have been allowed to share the results of their research with the NIH, says Portilla.
GE spokesman Conor McKechnie blames the "third parties" from which GE gained the rights to the EGFP protein for the onerous licensing requirements. But David Einhorn, house counsel at the Jackson Laboratory in Bar Harbor, Maine, which distributes mice to researchers around the world, questions GE's contention. He points out that many other mouse models that incorporate the gene for EGFP have been made and shared without objection from GE or from the institutions that originally discovered and licensed the EGFP patents.
Researchers have had trouble sharing resources for decades, but the situation seems to be getting worse. A 2007 study, for instance, found that 18% of academics' requests for research materials from other academic labs were not fulfilled (see 'Limited access') — almost twice as many as found in a survey taken during the 1990s. For materials requested from industry, the 2007 study found, one-third of academics' requests were declined (J. P. Walsh, W. M. Cohen and C. Cho Res. Pol. 36, 1184–1203; 2007).
Companies that don't want to share their resources don't usually publish papers describing them, says lawyer Tania Bubela of the University of Alberta School of Public Health in Edmonton, Canada. A publication changes the picture, she says. "The obligation of publication is to make your data and reagents available, so that people can replicate the results."
With no sign of a resolution, other labs have resorted to remaking the mouse model. Adrian Bird, director of the University of Edinburgh's Wellcome Trust Centre for Cell Biology, UK, says that his lab has re-engineered the mice and will distribute them through a repository, such as the Jackson Laboratory, as soon as his colony is large enough.
Bird and others say that it is unfortunate that scientists have had to delay research on the syndrome and spend money to regenerate a model that could already be in use.
"If you were to ask the families of people affected by this disease, they would say that every minute counts," says Bird.
Source: Nature News
Note: To see the original page click on the title of the post
Stashed away somewhere in a freezer in Cambridge, Massachusetts, is a mouse embryo that Etienne Joly would dearly like to get his hands on.
Joly is an immunologist based in Toulouse, France, with a keen interest in Rett syndrome, an incurable and debilitating disease that almost exclusively affects young girls. The mouse, developed by a team at the Novartis Institutes for Biomedical Research in Cambridge, carries a fluorescently tagged version of the gene that is mutated in the disease. It is the perfect tool, Joly says, for testing an idea he has about Rett syndrome. But a thicket of legal restrictions puts the mouse off-limits to anyone outside Novartis, even though scientists at the company are no longer using the model in their work on Rett syndrome.
"All scientists and families are asking for is the right to look into this disease and to try to understand it better," says Joly, who has embarked on a letter-writing campaign against the restrictions. "And when you know that there is a tool, but you can't use it because some lawyer says that you can't have the materials, then you get angry." Scientists and experts in intellectual-property issues say that the case shows how science can be impeded when onerous licensing rules govern the sharing of research materials.
Girls with Rett syndrome are healthy as babies, then progressively lose the ability to speak, move, eat and breathe normally. Because the disease is rare, affecting just one in 10,000 to 20,000 girls, it is an unattractive target for drug companies. Academic researchers have picked up the slack, and the field has moved at breakneck speed in recent years, from the 1999 discovery that defects in the gene MECP2 cause the disease, to clinical trials of possible treatments today.
Yet no one knows how the mutation causes the disease. A few years ago, Joly, who works at the Institute of Pharmacology and Structural Biology, came up with what he calls a "slightly unconventional" idea that the Rett-syndrome gene might have a role in regulating immune responses in the central nervous system. To explore his hypothesis, Joly needed an animal model that would allow him to trace where the gene is expressed.
In 2008, Joly learned about the engineered mouse. Led by molecular biologist Cecile Blaustein, the Novartis team had joined a copy of the mouse Mecp2 gene to a copy of the gene that makes enhanced green fluorescent protein (EGFP) to produce an animal in which the gene's activity can be traced throughout the brain and body (R. S. Schmid et al. Neuroreport 19, 393–398; 2008).
But after three years of trying, neither Joly nor any other Rett-syndrome researcher has been able to gain access to the mouse. When researchers asked to share it, Blaustein and her colleagues said that they would have liked to but couldn't because of the terms of Novartis's licence on EGFP, which it obtained from GE Healthcare.
Novartis and GE have been unable to negotiate a way to share the mice, says Jeff Lockwood, spokesman for the Novartis Institutes for Biomedical Research — even though Novartis has ended its research project on the mice.
When Monica Coenraads, executive director of the Rett Syndrome Research Trust in Trumbull, Connecticut, tried to broker an agreement to share the mice, GE and Novartis asked the US National Institutes of Health (NIH) in Bethesda, Maryland, to distribute the mice through its Mutant Mouse Regional Resource Centers. But Lili Portilla, senior adviser for technology transfer at the NIH National Center for Research Resources, which funds the resource centre, says that GE placed such burdensome terms on the sharing that the NIH eventually gave up. For instance, researchers would not have been allowed to share the results of their research with the NIH, says Portilla.
GE spokesman Conor McKechnie blames the "third parties" from which GE gained the rights to the EGFP protein for the onerous licensing requirements. But David Einhorn, house counsel at the Jackson Laboratory in Bar Harbor, Maine, which distributes mice to researchers around the world, questions GE's contention. He points out that many other mouse models that incorporate the gene for EGFP have been made and shared without objection from GE or from the institutions that originally discovered and licensed the EGFP patents.
Researchers have had trouble sharing resources for decades, but the situation seems to be getting worse. A 2007 study, for instance, found that 18% of academics' requests for research materials from other academic labs were not fulfilled (see 'Limited access') — almost twice as many as found in a survey taken during the 1990s. For materials requested from industry, the 2007 study found, one-third of academics' requests were declined (J. P. Walsh, W. M. Cohen and C. Cho Res. Pol. 36, 1184–1203; 2007).
Companies that don't want to share their resources don't usually publish papers describing them, says lawyer Tania Bubela of the University of Alberta School of Public Health in Edmonton, Canada. A publication changes the picture, she says. "The obligation of publication is to make your data and reagents available, so that people can replicate the results."
With no sign of a resolution, other labs have resorted to remaking the mouse model. Adrian Bird, director of the University of Edinburgh's Wellcome Trust Centre for Cell Biology, UK, says that his lab has re-engineered the mice and will distribute them through a repository, such as the Jackson Laboratory, as soon as his colony is large enough.
Bird and others say that it is unfortunate that scientists have had to delay research on the syndrome and spend money to regenerate a model that could already be in use.
"If you were to ask the families of people affected by this disease, they would say that every minute counts," says Bird.
Source: Nature News
Note: To see the original page click on the title of the post
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