BioWorld International Correspondent

LONDON - Clinical trials to evaluate a treatment for glaucoma could begin within two years, following recent successful studies in animals in which the success rate of eye surgery rose from 30 percent to 80 percent. The discovering researchers believe the therapy, which is able to suppress the formation of scar tissue in the eye, also could have applications in damping down the immune response in conditions such as septic shock.

Sunil Shaunak, professor of infectious diseases at Imperial College London, at the Hammersmith Hospital, told BioWorld International: "We have invented sugar-like molecules that are similar to those found in the body, which are able to trick the body into thinking that the injury that has occurred is much less severe than it really is. The result is a beautiful repair of the tissue without all the damage normally associated with repair of injury."

Shaunak, together with Steve Brocchini of the biomedical polymers group at the University of London's School of Pharmacy, plans to exploit the discovery through a spin-off from the university called PolyTherics. They are looking for commercial backers to help develop the work.

An account of the study is in a paper in Nature Biotechnology, published online July 18, 2004. Its title is "Polyvalent dendrimer glucosamine conjugates prevent scar tissue formation."

The sugar-like molecules in question are called dendrimers. Those are large, highly branched molecules that can be chemically synthesized and engineered in a variety of ways. Research by Shaunak and colleagues suggested that particular arrangements of the end groups of dendrimers could provide the molecules with biological properties, by virtue of their ability to interact with cell-surface receptors and their ligands. In particular, the group identified two molecules that appeared non-toxic, one of which seemed to modulate the immune response. The other seemed to suppress the formation of new blood vessels.

Having completed initial tests on cell cultures to establish the function and lack of toxicity of the compounds, the group focused on evaluating their therapeutic use in an animal model of glaucoma.

Glaucoma is the most common cause of blindness worldwide. It develops when pressure inside the eyeball increases, causing damage to the optic nerve. If left untreated, blindness results.

One common treatment is to insert a small tube inside the eyeball in order to drain excess fluid from the eye and relieve the pressure. However, that often fails when scar tissue builds up around the end of the tube and blocks it.

Shaunak said: "We knew that much scarring as a result of surgical injury results from the recruitment of white cells to the area and from the growth of new blood vessels. We had these dendrimers that we knew could control these processes, so we wondered whether we could use them to trick the body into thinking that there was an injury that needed to be repaired, but without forming scar tissue."

The molecules they made and used were dendrimer glucosamine, which prevents recruitment of white cells to the area of injury, and dendrimer glucosamine 6-sulfate, which stops the growth of new blood vessels.

"We chose to test the compounds in an animal model of glaucoma," Shaunak said, "because the readout is very simple, and the results are very clear: If the tube stays open, the surgery is a success; if it blocks, the surgery is a failure."

The results, he said, were "interesting and impressive." The success of surgery rose from 30 percent to 80 percent. Subsequent histopathological studies showed no evidence of scar-tissue formation.

Clinical trials in humans are expected to begin at Moorfields Hospital in about two years' time, once regulatory and ethical approval has been obtained.

The applications of the new therapy could be much broader, Shaunak added. "First, it is possible that patients with injuries such as severe trauma and extensive burns could benefit from a treatment such as this," he said. "Second, we know that in infectious diseases, antibiotics can kill the bacteria in two days - but we then spend another 10 days managing the problems created by the immune system, as in septic shock, for example. So we need to explore whether these new sugar molecules can manipulate the immune system in order to control the injuries that result when it overreacts."

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