When a Llama Is Laid Back, It's Not the Only Beneficiary

[question everything]

FEBRUARY 17, 2009

When a Llama Is Laid Back, It's Not the Only Beneficiary
By MATTHEW DALTON
WSJ

The engines of innovation for a promising new class of pharmaceuticals are covered in soft hair and tend to spit when irritated. Scientists are exploiting an unusual feature of the immune system of llamas -- a South American relative of the camel -- to develop new treatments for diseases including rheumatoid arthritis, cancer and Alzheimer's. Llamas, camels and their alpaca relatives are one of only two animal families that create extremely small antibodies, the molecules that are the soldiers of the immune system.

Antibody technology has produced a number of blockbuster drugs over the past decade, such as the cancer treatments Avastin and Erbitux and the arthritis drug Enbrel. Antibodies can be programmed to target proteins that are responsible for diseases, just like a vaccine prepares the immune system to fight viruses. They deliver drugs directly to the troublesome proteins responsible for the disease or block the action of the proteins themselves, stopping the progression of the disease. But conventional antibodies are large, complex molecules that aren't very durable and have trouble finding their way around the body's tiny crevices. Scientists hope the tiny antibodies found in llamas and camels -- about one-tenth the size of human antibodies -- can burrow into the densely packed cells of a cancerous tumor, slip their way through the blood-brain barrier to block the build-up of plaques that cause Alzheimer's, or settle into the crevices of joints to prevent arthritis.

A major problem is that it sounds too good to be true, said Serge Muyldermans, director of the Cellular and Molecular Immunology lab at the Vrije Universiteit in Brussels and one of the founders of Ablynx, the Belgian biotech firm that has the patents on using llama and camel antibodies. "The only disadvantage they have is we can't find a disadvantage. People don't believe us any more."

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Drugs using larger antibodies usually must be injected, because the antibodies will be destroyed in the stomach or the lungs. But smaller antibodies are more resistant to such extreme environments, which means the drugs can be taken orally or by inhaler. Smaller antibodies can also be grown using bacteria, much cheaper than using the mammal cells needed to grow large antibodies... And it's possible to stitch together different kinds of these antibodies, producing a molecule that can target several different proteins at once. Scientists expect this will be particularly useful for blocking the growth of cancerous tumors, which typically involve the action of several different proteins.

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Despite their promise, no one knows whether drugs using small antibodies will work in humans. The first drugs are still several years away from being approved for medical use. Ablynx is probably closest to putting a product on the market -- a drug to prevent blood clots that tend to form in patients who have had stents implanted to open a blocked artery. If the drug passes all its clinical trials, it could be on the market in 2012 or 2013, said Ablynx Chief Executive Edwin Moses. Ablynx -- which calls its llama antibodies "nanobodies" -- also has a partnership with Wyeth to develop a new arthritis drug that will use nanobodies to block TNF alpha, an immune-system protein that causes the inflammation characteristic of rheumatoid arthritis. Wyeth is hoping the Ablynx drug will help replace its blockbuster arthritis treatment, Enbrel, when the drug's patent expires after 2011. "In the lab, the nanobodies have actually performed spectacularly," said Davinder Gill, vice president of biological technologies at Wyeth Research. The drug is in the first stage of human clinical trials.

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http://online.wsj.com/article/SB123483846519396567.html (subscription)

[LeftishBrit]

1. Fascinating

[trotsky]

2. Big Yak will not tolerate this competition.

Gentlemen, ready your tinfoil.