windfall. white arrows indicate weaknesses in the blood vessels of mice with HHT ( environment) than healthy mice ( left ) did not. Thalidomide strengthens the vessel walls ( right ).
Lebrin et al, Nature Medicine, Advance Online Publication (2010)
Despite its horrific history of causing birth defects, thalidomide has recently made a comeback as a treatment for diseases such as multiple myeloma cancer. Now, a new study suggests that the drug may also relieve symptoms of a genetic disease called hereditary hemorrhagic telangiectasia, a discovery that could help researchers to new therapies for VRL and other vascular diseases.
In the late 1950s and early 1960s, doctors prescribed thalidomide as an anti-nausea drug for pregnant women with a regularity that proved tragic. More than 10,000 children in 46 countries were born with missing limbs and other defects before thalidomide manufacturers have pulled from the market. Researchers have recently begun to understand how the drug made its damage. They know little about one of the benefits of the drug Thalidomide appears to control angiogenesis, the growth of new blood vessels. This property makes it a powerful weapon against some cancers, but scientists do not know how it works.
In HHT, blood vessels grow without the right support cells to maintain stable and solid. Patients have leaking vessels and are subject to potentially fatal bleeding in the brain, lungs, liver and gastrointestinal tract. People with the rare hereditary disease also have frequent nosebleeds, as much as seven a day, which can become so severe that patients require skin grafts in their nose or even more desperate measures to lead a normal life. "Patients VRL get their nostrils sewn just so they can walk down the street," says Christine Mummery, a developmental biologist at the Medical Center of the University of Leiden in the Netherlands.
The addiction thalidomide for targeting blood vessels in tumors is Mummery ask whether the drug's effect on angiogenesis could help people with HHT. When they gave thalidomide seven HHT patients, six had significantly fewer nosebleeds in the month of their first dose, Mummery and his colleagues report online today in Nature Medicine .
to find the mechanism underlying the improvement of patients, researchers tested the drug on mice high to have HHT symptoms. They found that although high doses of thalidomide stop angiogenesis, lower doses actually strengthen blood vessels by stimulating cell growth. Thalidomide seems to pair with a growth factor called PDGF-B to produce more smooth muscle cells that repair defects walled container.
The evidence suggests that the drug works the same way in humans. A nasal biopsy seventh participant (which also saw an improvement, but had to abandon the study because of nerve damage caused by thalidomide) showed layers of smooth muscle cells more than were present in samples from untreated HHT patients. The findings offer new insight about how thalidomide which affects the blood vessels, says Mummery.
They also offer people with HHT hope for more effective therapies in the future, said Paul Oh, an experimental geneticist at the University of Florida, Gainesville, who was not involved in the study. "It is possible thalidomide help with all aspects of HHT," he said. "This is the first major treatment of HHT community works."
The study could well point the way to a more alternative safe, says Rosemary Akhurst, a molecular biologist at the University of California, San Francisco. "ultimately, we do not want anyone to be using a dangerous drug thalidomide," she said. "This can we help take the positive aspects and leave the negative. "
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