LCT cheered by diabetes preclinical results

Auckland-based, Australian-listed biomedical company Living Cell Therapies (ASX:LCT) is elated at the results of a six-month preclinical trial of its DiaBCell encapsulated-cell therapy for diabetes in monkeys.

The five monkeys in the experimental group all showed significant responses to the therapy for type 1 (insulin-dependent) diabetes, the company said.

The trial, designed to test the safety and tolerability of the therapy, used a minimal dosage to minimise the risk of adverse reactions, but one animal responded so well that researchers were able to wean it off insulin injections entirely at nine months.

"We're pretty pleased to get this sort of result in a first-up trial, and if we can get a similar result in a Phase I human trial, we'll be cracking the Moet," said LCT's chief medical officer, Prof Bob Elliott.

The company treated five diabetic cynomolgous monkeys with DiaBCell capsules, injected into the peritoneal cavity. The permeable alginate capsules contain living, insulin-secreting pancreatic islet cells from pigs.

The cells, from a specially inbred strain of pig, respond in a physiologically normal manner, secreting insulin in response to rising levels of glucose in the bloodstream, and reducing secretion as excess glucose is shunted into storage in the liver.

Elliott developed the biocompatible alginate capsules to be permeable to glucose and other biomolecules in the bloodstream, while excluding immune-system cells that would otherwise attack and destroy the pig cells.

Seven monkeys received two small doses of DiaBCell three months apart, at a rate of 10,000 microcapsules per kilogram of body weight. The control group received blank capsules as a placebo, at the same rate and interval.

Two of the animals -- one in the treatment group, the other in the control group -- died early in the trial, of complications unrelated to the treatment, LCT said.

After three months, five of the animals in the experimental group registered reductions in supplementary insulin injections, while two required increases. In contrast, six animals in the placebo group required increased amounts of insulin as the trial proceeded, while one registered a 14 per cent reduction.

Elliott said the trial was the largest controlled diabetic study of its kind in the world, and while it was designed primarily to test safety and tolerability, the indicated efficacy demonstrated that it would be a major step forward in treating diabetes if it could be replicated in human diabetics.

Elliott said insulin production from the encapsulated cells peaked at between five and 10 weeks, and declined slowly thereafter, with no sign of hypoglycaemia. Researchers re-treated the monkeys after three months, to maintain their insulin output, even though production declined by only a small amount towards the end of the first three-month period.

Elliott said the wide range of variation in responses in the treatment group may reflect individual differences in the monkeys' response to insulin. In this, they were probably mirroring variation in human diabetics, whose individual requirements range between 30 and 100 units of insulin a day.

If the therapy reaches human clinical use, dosage would probably be adjusted according to diabetics' individual requirements for insulin, rather than given a standard dose based on bodyweight.

Elliott said the real advantage of LCT's diabetes therapy was that it would provide a large margin of safety, because the living cells modulate their output to match the body's insulin requirements -- just as pancreatic islet cells do in non-diabetics. "But we now know we can give the therapy safely, and more than once, and still get a good response," he said.

LCT's CEO, David Collinson, said his company was "very encouraged" by the data, and would now increase its efforts to complete the rest of the necessary preclinical work and documentation to support its US Food and Drug Administration Application for registration as an investigational new drug later this year.

Collinson said ongoing pre-clinical studies would provide additional information on the long-term viability and function of islets recovered from diabetic monkeys, and LCT would also direct resources to its pig and cell-processing facilities to ensure sufficient supply of DiaBCell for human clinical trials.

Elliott will present details of the study to two major diabetes research forums later this year.