Hong Kong role in pig cell-based alternative to human liver transplant

A pioneering United States-based company is using cells from 15 specially-bred piglets supplied by the Chinese University of Hong Kong in order to create a life-saving alternative to human-to-human liver transplant for seriously-ill patients.

The research is being led by Excorp Medical Inc’s president Dr Daniel Miller. The firm is also establishing a facility in Hong Kong, a city with advanced liver treatment programmes but one that also has an acute shortage of suitable human donors for local patients. The group is also mulling listing an entity on the Hong Kong Stock Exchange.

Unlike an organ transplant, the ground-breaking technology does not need to be fitted inside the patient’s body.

Annually in the U.S. alone, 9,000 patients on the liver transplant waiting list are unable to secure a suitable match, and at least 1,400 of them die in any given 12-month period while they wait, according to media reports.

Physicians and other scientists have been trying for decades to look for alternatives to human liver transplant – via use of either charcoal, reverse osmosis, or ion exchange technology – in attempts to flush otherwise fatal toxins from the blood. Creation of artificial organs has so far been impossible, chiefly because the human liver performs a myriad of metabolic functions that cannot be substituted by simple physical procedures.

The most effective alternative scientists have come up with so far is to utilise individual animal liver cells, using them collectively to perform certain functions.

Dr Miller and his team developed what is termed a “bio-artificial” detoxifier, which he claims is a world first. It remains outside the patient’s body, and uses piglet liver cells. The Bioartificial Liver System “is a life-saving procedure designed to remove toxins from the blood that cannot be filtered adequately by the failed liver,” while buying the patient’s ailing organ time to repair itself, Dr Miller told Innovation Hong Kong.

“We have presented the first clinically-effective case of providing short-term metabolic support for patients with acute liver failure.Our goal is to either bridge the patient-to-transplant [process] or to bridge the patient-to-liver regeneration [phase].”

 

How it works

 

The system developed by Excorp Medical works in effect as a temporary liver: it contains a blood pump, an oxygenator and a bioreactor, linked by tubing. During the 12-hour treatment session, the blood will be cleansed by circulating through the device outside the body before going back into the patient.

The blood pump will first draw the patient’s blood from a vein and into the Bioartificial Liver System. A medication called heparin is injected into the blood, before the blood is passed to the oxygenator. At that stage dioxide carbon is also added to the blood in order to bring its pH value back to a normal human range. Then the blood travels through the bioreactor – a cartridge filled with piglet liver cells designed to metabolise the toxins in the blood – and then back into the patient’s body.

“The function of the liver has been conserved through [animal] evolution so it is the same with pigs today as it is with humans,” Dr Miller told us. “The metabolic activity of the pig liver cells in this level of the process replicates the human liver’s function almost exactly”.

The cells from piglets supplied by the Chinese University of Hong Kong are a better fit for the system developed by Excorp Medical than cells from adult pigs, because the proportion of a pig’s liver to its body mass becomes lower as the animal matures. Cells from two piglet livers are enough to fill five bioreactors, with each one storing up to 100 grammes (3.5 ounces) of pig cells.

 

Recovery time

 

Patients with acute liver failure often suffer from serious complications, including excessive pressure on the brain, bleeding disorders, infections or kidney failure, and they can end up in coma. In many cases the situation can be reversed once toxins are removed from the blood, giving a chance for the patient’s own liver to regenerate itself to some extent.

 

The Bioartificial Liver System can restore consciousness to a comatose patient four to five hours into the treatment, because “the situation reverses almost immediately,” Dr Miller said. “It caught us by surprise when it happened for the first time.”

The system has been some 20 years in the making. The first two phases of clinical trials, involving a total of 15 enrolled patients –10 control patients and five patients undergoing actual treatment – began in the year 2000, and demonstrated the system can work on unstabilised patients with severe liver failure, without compromising their condition in other ways, or interfering with other clinical therapies the patient might already be undergoing.

The treatment developed by Excorp Medical is expected to have a cost of US$10,000 per patient, said Dr Miller. He noted that was less than a quarter of the cost of a liver transplant.

Dr Miller is bringing the technology to Hong Kong via a facility employing approximately 30 staff at the Hong Kong Science and Technology Park, which will serve as a laboratory for research and bioreactor production. Initial studies are likely to be conducted at Queen Mary Hospital, which is well known for its work on liver transplant surgeries. Private hospitals are also likely to be involved in the work.

The city’s shortfall in hospital intensive care beds relative to its population presents challenges when thinking about scaling up the use of Excorp Medical’s technology, noted Dr Miller. The company is exploring the possibility of cooperation with hospitals in the neighbouring mainland city of Shenzhen as a next step, he said.

 

Possible HK listing

 

So far there are 350 individual investors on board worldwide, supporting the work of Excorp Medical: five are in Hong Kong.

“We are in the process of restructuring the company into an Asian-based holding company. The headquarters is in Singapore, while Hong Kong is the holding company for our China operations, and also for the purpose of starting clinical trials in China,” Dr Miller said. He added the group was mulling applying to list an entity either in the United States or in the Hong Kong bourse.

“The company has met with officials of both Nasdaq [in New York] and the Hong Kong Stock Exchange to explore the options and the interplay between the two markets. No other exchanges are being considered at this point. Timing, of course, is subject to events not entirely under our control,” he told us.

Excorp Medical is one of a number of U.S. medical technology firms looking to tap China’s burgeoning middle class and the Chinese government’s increasing investment in healthcare. Entry to the mainland China market – which Excorp Medical thinks could be very interesting for the company – is high on its agenda.

Dr Miller is looking to shift manufacturing to mainland China in two years with a factory employing up to 400 people. “China has an important part to play, not only because it is the largest single market in terms of number of patients, but also because of the China Food and Drug Administration, a regulatory body that can offer effective review of our data, allowing us to market the system in the country while generating credibility in the international community of liver specialists,” he said.

In mainland China, around 383,000 people die from liver cancer every year, accounting for 51 percent of the deaths from liver cancer worldwide. Dr Miller acknowledges the firm faces challenges common to medical technology businesses seeking to enter the mainland China market.

“U.S. products that are designed for the U.S. market have oftentimes not worked in Asia,” said Dr Miller. “This is largely driven by the fact that we have an enormous doctor base in the U.S. per patient, whereas China will never have enough doctors to approach that ratio of doctor to patient,” he added.

“What we can afford to do in the U.S., you can’t afford to do here,” he further noted, citing high prices of patented medical drugs in mainland China.

Dr Miller is enthusiastic about other medical technologies that can be marketed to China, since his specially-bred piglets can be used in many other medical fields such as the production of heart valves, correcting haemophilia, replacing burnt skin, or for the treatment of the pancreas in cases of diabetes.

“Once we establish a volume of production and get everybody comfortable with the medical use of pigs, then we’ll be able to use it [the cell material] for these other purposes,” he told us.

 

 

 

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