LCT elated by Huntington's preclinical study

Auckland-based Living Cell Therapies (ASX:LCT) today announced "extraordinary" results from its preclinical trial of alginate-encapsulated pig brain cells in a primate model of Huntington's disease.

LCT medical director Dr Bob Elliott was elated at the result, and said the company would now apply to the US Food and Drug Administration to conduct a trial in human patients in the US as soon as possible.

Elliott said the company also plans to proceed at full-speed towards a trial of the same therapy in patients with other neurodegenerative disorders including Alzheimer's disease, Parkinson's disease and motor neuron disease.

Elliott told Australian Biotechnology News that, given the consistent results of trials of LCT's NeutrophinCell (NtCell) therapy in rat and primate models of Huntington's disease, he believed that the FDA approves its use in human patients, early diagnosis early intervention could allow patients who would normally expect to die prematurely from the devastating neurodegenerative disorder to live normal lives.

A team led by LCT's VP of research, US neurodegenerative diseases specialist Dr Dwaine Emerich, implanted tiny alginate capsules the brains of six cynomolgous monkeys.

Three of the monkeys received capsules containing pig choroid plexus cells, a type of long-lived epithelial cell that secretes cerebrospinal fluid containing a cocktail of protective neurotrophins -- nerve growth cell factors.

Emerich's team used high-precision stereotactic surgery to precisely implant the tiny capsules into the striatum, the region of the brain that

All the monkeys subsequently received injections of quinolinic acid, another natural compound produced in the brain, which at high doses kills the neurons of the striatum, precisely replicating the damage seen in advanced Huntington's disease.

One month after the quinolinic acid insult, the three monkeys that had received the choroids plexus cell implant showed only a fifth of the neuron loss of the monkeys implanted with the cell-free alginate biocapsules.

The biocapsules, around half a millimetre in diameter, are permeable to neurotrophins produced by the encapsulated cells, but exclude antibodies and natural killer cells that would otherwise recognise the pig cells as foreign, and destroy them.

LCT's CEO Dr Al Vasconcellos said the significance of the result, from the company's perspective, was that many experimental treatments for Alzheimer's, Parkinson's and other neurodegenerative diseases worked well in mouse models, but failed to 'scale up' in the human brain, which was at least 500 times larger.

"Adapting treatment modalities to maintain the therapeutic benefit as brain volume increases is not a trivial problem," Vasconcellos said. "In terms of supporting the case we will put to the FDA for a clinical trial, and demonstrating the product platform, these results are quite extraordinary."

Emerich said, "For the first time, we have provided evidence that we may be able to prevent Huntington's patients' loss of neurons. We've known for a long time there are potentially efficacious treatments, but the problem has been to deliver them into the brain."

Vasconcellos said an exciting aspect of the result was that Huntington's was a terminal disease that was both incurable and untreatable. "But it's well marked genetically," he said. "Unlike many other diseases treated by modern medicine, we can diagnose patients while they are still asymptomatic.

"The build-up of the protein toxin in Huntington's patients in the real world occurs very slowly, over many years. The quinolinic acid treatment is rapidly toxic, a sledgehammer in comparison.

"If we can protect the majority of nerve cells against acute toxicity in the primate model, we should have a lot more time and flexibility in human Huntington's patients."

Xeno barrier

LCT is applying to the FDA to test the therapy in US patients because Australian and New Zealand legislation currently prohibits xenotransplantation -- the transplantation of living cells from a non-human species into humans.

The xenotransplantation ban recognises the potential risk of dormant retroviruses in the pig cells' genome reactivating and causing an AIDS like epidemic -- a risk that appears to have been overstated, according to Elliott, given that several patients implanted with alginate-encapsulated pig cells a decade ago have shown no adverse effects, even though the capsules would have broken down long ago.

Asked about how often the procedure might have to be repeated to maintain a protective benefit, Elliott said that the cells should continue to secrete neurotrophins for at least the normal lifetime of a pig -- around 20 years, although the capsules would probably break down well before the cells expired.

Depending on the severity of the mutation, patients who inherit the Huntington's gene from one or the other parent can develop the early symptoms of the disease as early as age two, but typically, in manifests in mid-life.

New evidence suggests symptoms of cognitive decline, and memory impairment, may develop some years before the disorders more florid symptoms, which include dementia, depression and violent, uncoordinated movements, or 'chorea'.

'Tony', a spokesperson for the New Zealand Huntington's Disease Association, who has undergone the gene test, and is at risk of developing the disorder, today told journalists it was very likely that the news of a potentially successful therapy would induce more individuals in families with a history of the disorder to undergo DNA testing.

He said only a minority of individuals in affected families currently opt to undergo testing for the disorder because it is incurable, and they prefer to live with uncertainty, rather than certainty.

LCT said Huntington's disease currently costs the US healthcare system more than $2.5 billion annually, and LCT's NtCell therapy had the potential to meet a $700 million market.