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San Diego Firm Hopes to Help Diabetics With Insulin-Producing Pig Cells

Posted on: Friday, 2 December 2005, 09:00 CST

By Terri Somers, The San Diego Union-Tribune

Dec. 2--Pigs, polymer and a quiet San Diego biotechnology company are making some diabetics and their doctors hopeful.

Scientists at MicroIslet in Sorrento Mesa are taking insulin-producing islet cells out of pigs and coating them in a polymer derived from seaweed. The insulin-producing cells, which are needed to regulate blood sugar, go through this process in preparation for injection into the abdomen of people with diabetes.

Once transplanted into diabetics, the polymer is supposed to keep the human immune system from attacking the foreign cells and allow the pig islets to secrete insulin.

Ideally, the process would eliminate the diabetic's need to take insulin injections.

Doctors who are pioneering the transplantation of human islet cells into diabetics view the encapsulated pig cells as a possible solution to two of the biggest problems in such transplant procedures: a shortage of donor islet cells and rejection of the donated cells.

"To use pigs as a source to treat patients, which is the ultimate goal, and to have it done safely and replace insulin injections would be the treatment of choice for people with Type 1 and Type 2 diabetes," said Dr. Daniel Salomon, a researcher at the Scripps Research Institute.

Salomon is among a small group of physicians who have successfully transplanted human islet cells from donor organs into diabetics, a process known as the Edmonton Protocol. He is also on MicroIslet's scientific advisory board.

"There needs to be ongoing and very careful, stringent testing to be sure the safety is sound and the efficacy of approach is sound," Salomon said. "But eventually, this is going to happen."

But such strong proclamations are not flying out of MicroIslet's public relations department.

"I don't want to overhype," company president Haro Hartounian said. "When you're talking about a cure for diabetes, you're dealing with the emotions of millions of people."

Other companies are developing similar technology, including Novacell in Irvine.

When asked about his competitors, Hartounian remains optimistic and low-key: "Our (scientific) data can speak for itself."

From the company's founder, who has Type 1 diabetes, to the scientists who slaughter the pig, remove its pancreas and extract the islet cells, the prospect of helping more than 20 million Americans who have diabetes fuels MicroIslet's 28 employees to work long days.

"Islet transplantation is the answer to treating people with Type 1 diabetes," said Chief Executive Officer John Steele, who was diagnosed with diabetes more than 24 years ago. "Insulin is difficult to regulate, and being human, people make a lot of mistakes and fail to comply with their proper regime. The disease also has long-term complications, (such as) neuropathy, blindness, and kidney failure that can lead to death."

For two and half decades, Steele has pricked his fingers several times each day to check his blood sugar. And he's injected himself with insulin thousands of times.

His illness and its side effects will continue to progress, he said, unless an alternative therapy is developed.

In people with Type 1 diabetes, the immune system attacks and destroys insulin-producing islet cells. Insulin injections are not a cure for this, Steele said.

But islet transplantation comes closer, he said.

When Steele, a biotech entrepreneur, first heard of transplantation, he studied what had been written about the science. And he read about work that was being done to encapsulate donor cells in an attempt to avoid rejection.

Encapsulation technology has been around for about 20 years, and there was great interest in it about a decade ago. But the hype over its promise quickly faded.

Steele saw the technology as an opportunity and founded MicroIslet in 1998.

Then he started looking for a scientist to improve the process.

He found that man, Hartounian, living in Del Mar. Hartounian, a chemical engineer, had worked at Pharmacia, the largest producer of biopolymers.

In the years since licensing the encapsulation technology, researchers at MicroIslet have been trying to perfect their technique.

When Salomon first learned about MicroIslet, he was intrigued with the idea.

"The concept that one can use modern biomaterials to protect islets from the immune system is scientifically sound, and it converts everything into an engineering problem," Salomon said.

Over the last several years, a significant amount of progress has been made on several of the key challenges in bringing islet cells to the forefront.

No. 1 is the ability to produce consistently high-quality, high-yield pig islet preparations, he said.

"Sure scientists can do it in a lab once in a while. But can they do it consistently and well in large numbers and build a commercial process?"

MicroIslet has done that, he said.

The pigs are supplied through an exclusive contract with the Mayo Clinic, where they are raised to be free of disease.

Several times a week, fat, pink Yorkshire pigs are slaughtered an an undisclosed location in San Diego and their pancreases removed. The pancreases, each about as long as a football but just an inch or two thick, are transported to MicroIslet's lab.

Outside the lab where the islet extraction takes place, someone has tacked to the wall a drawing of a pretty and plump pink pig, covered in pearls.

Excess fat and tissue are carefully cut away from the pig pancreas, much like a cook trims fat and skin from a roasting chicken.

The pancrease is eventually placed in a bag filled with an enzyme soup, which breaks down the tissue and allows the islet cells to be extracted. Islet cells make up only 2 percent to 3 percent of the organ.

Once the cells are harvested and purified, an electromagnetic procedure is used for encapsulation, Hartounian said.

The islet cells and the coating -- a biocompatible, biodegradable product derived from seaweed -- are electrically charged. When they collide, an ion exchange occurs and encapsulates hundreds of islet cells into uniform sized capsules. Each capsule is the circumference of about six human hairs.

"Once the pig cells are encapsulated, the coating makes them appear transparent to the body into which they are transplanted," Hartounian said.

That means the recipient's immune system does not identify the transplant as a foreign body that could cause infection and therefore does not try to attack it.

Such autoimmune system reactions are a great hurdle in the transplantation of human islet cells, said Dr. James Shapiro of the University of Alberta in Canada. Shapiro developed the Edmonton Protocol and has performed 85 of the 550 procedures done worldwide.

"While the procedure is good, the side effects from the (anti-rejection) drugs can be very difficult," Shapiro said. Besides having to take a large number of pills that suppress the immune system, patients can become more susceptible to other illness. Some people cannot tolerate the drugs. And some patients reject the islet cells despite the drugs.

All of these factors prevent the protocol from being used on children.

Eliminating the rejection issue would open up the field to treating many more people, possibly even children, he said.

Stem cell therapy may one day lead to other options. Researchers believe they eventually may be able to grow human islet cells from stem cells.

However, rejection issues would persist unless stem cell therapies can be developed to grow islet cells specific to an individual.

While that sounds great in theory, Salomon said, it is at best probably decades away.

In the meantime, Hartounian and Steele think pigs provide the solution.

"We diabetics are cell source agnostic," Steele said. "We just want it to work at treating our diabetes."

MicroIslet's technology has been tested successfully on mice and larger animals, Salomon said.

The company hopes to get approval from the Food and Drug Administration to begin safety and efficacy tests on humans within 12 to 18 months, he said.

But finances appear to be as much of a hurdle as the complicated science. At the end of the third quarter, MicroIslet reported $4 million in cash and cash equivalents. In recent years, the company has burned through $600,000 monthly.

A National Institutes of Health small-business innovation research grant for $1.7 million over three years will help the cash crunch and is validation of the company's technology, Hartounian said.

Additional validation, he said, can be found in the members of the company's scientific advisory board. Salomon is a special government employee for the FDA and has served in several national advisory positions regarding transplantation.

The company has been publicly traded since 2002, but its executives still consider MicroIslet "very closely held."

Four years ago, MicroIslet and many other biotechs were having a hard time raising money. One funding option developed would have required the company to give 50 percent ownership to a private investor.

Its leaders decided that instead they would go public through a reverse-merger, give up 15 percent ownership and raise $4 million at $6 a share.

"It's considerably easier for a small public company to raise money than a private life science company," Kachioff said.

With dwindling cash and the hope of starting clinical trials, funding is a daily concern.

Hartounian said the company isn't spending lavishly. For example, he said, the staff size has been kept to a minimum.

"Unlike other companies, we don't have hundreds of people on the payroll. The time to expand is in Phase 1 clinical trials, when we'll beef up clinical development and regulatory affairs."

"Our intention is not to raise more than we need right now," said William Kachioff, chief financial officer. "We believe that when we get approval to begin trials there will be a higher level of excitement in the market and we will raise more money at that time."

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Source: The San Diego Union-Tribune

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