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Winter - Classical MileEnd Alpacas

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From<br />

Dromedary<br />

to Drugs<br />

Could a unique type of antibody found<br />

in the blood of camelids hold the key to<br />

unlocking cures for many dibillitating<br />

human diseases ?<br />

Henry Nichols reports on the success of<br />

current research<br />

Discovery<br />

In the late 1980s, Belgian immunologist<br />

Raymond Hamers, then at the Free<br />

University of Brussels (VUB), found<br />

himself confronted by a couple of bold<br />

undergraduates. The practicals for their<br />

course were just too predictable, they<br />

complained. Could he find them an<br />

original research question to answer?<br />

Hamers remembered half a litre<br />

of camel serum sitting in a freezer.<br />

Although he had it stashed away for<br />

some ongoing research into sleeping<br />

sickness, he reckoned he could spare a<br />

bit for his students to play around with.<br />

"Why don't we see if we can purify camel<br />

antibodies?" he asked.<br />

The results were so unexpected the<br />

students were flummoxed. For a time, so<br />

too was Hamers. The diffusion pattern<br />

of antibodies isolated from the serum<br />

suggested that in addition to the type of<br />

antibody found in all other vertebrates,<br />

the camel also produced a smaller and<br />

entirely novel variety.<br />

They went on to demonstrate this<br />

immunological phenomenon is not just<br />

limited to the dromedary. Other camelids<br />

– the Bactrian camel, llama, alpaca,<br />

guanaco and vicuña – also have the same<br />

resilient slimline antibodies.<br />

In the scorching heat in the heart of downtown Dubai, a herd of dromedary<br />

camels is chewing the cud. These majestic beasts, owned by Sheikh<br />

Mohammed bin Rashid Al Maktoum, are living it up in retirement at the city's<br />

Central Veterinary Research Laboratory. But their lives are far from over. In fact,<br />

these animals could be behind something of a medical revolution.<br />

A chance discovery in the late 1980s revealed that camelids have an extraordinary<br />

immune system unlike that of any other mammal: in addition to normal antibodies,<br />

their blood also contains a miniature variety. Belgian immunologists are working<br />

with the Sheikh's dromedarys to isolate and use these small antibodies as the basis<br />

for 'nanobodies' – tiny proteins about one tenth the size of conventional antibodies<br />

but capable of the same defensive skills.<br />

Nanobodies are so exciting because they can get to parts of the body conventional<br />

antibodies cannot reach. They are less prone to destruction by enzymes and it's<br />

possible they could even be taken in tablet form rather than by injection. Since they<br />

are far simpler than larger antibodies, they are much easier to manufacture and<br />

hence cheaper. The results of the first nanobody-based therapy to enter clinical<br />

results are expected soon.<br />

Antibodies are a key component of the vertebrate immune system, chunky Y-<br />

shaped proteins let loose in the bloodstream or tethered to immune cells. They<br />

are designed to bind to a specific target on a foreign object and bring about its<br />

destruction. In the mid-1970s, scientists worked out how to manufacture these<br />

cunning little proteins in the laboratory. The ability of these so-called 'monoclonal<br />

antibodies' to bind to a target of choice gave them a serious advantage over<br />

conventional drugs, which are not particularly specific and can have all sorts of<br />

side-effects.<br />

But 30 years on, there are only around 20 therapeutic antibodies on the market,<br />

largely because making them is a lengthy and expensive procedure. This has fuelled<br />

a demand for molecules with antibody-like properties that perform as well but are<br />

structurally simpler. Camels and their relatives might offer the solution.<br />

The arms of a conventional antibody are made from two complimentary peptide<br />

32 Alpaca World Magazine <strong>Winter</strong> 2007 / 08

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