Doctor here to solve diabetes
BY TIM BONFIELD
The Cincinnati Enquirer
Even though Steve Santen takes five to seven insulin injections a day and checks his blood sugar constantly, he fears for his future health.
As one of the estimated 1 million Americans with Type I diabetes, he worries about his chances of going blind, of having his feet amputated or winding up hooked to a dialysis machine hoping for a kidney transplant.
Unlike most Greater Cincinnati residents, Mr. Santen has already heard of Dr. Horacio Rilo, a researcher recruited here four months ago from the University of Chicago. With the hiring of Dr. Rilo, the University of Cincinnati and the Children's Hospital Medical Center are joining a national quest for the Holy Grail of diabetes research islet cell transplantation.
The National Institutes of Health, the Juvenile Diabetes Foundation and other groups have invested millions into islet cell research. Success would not only lead to a cure for diabetes, but could create technology that might also improve care for liver disease and other illnesses.
'The thing about islet cell transplantation is that no one has done it successfully. If this works, it's a big deal,' Mr. Santen said. 'You're talking about restoring normal life for thousands, maybe millions of people.'
Islet cells are the insulin-producing part of the pancreas. Diabetes occurs when the pancreas fails to function properly. That means a pancreas transplant can cure diabetes, but researchers believe many more people stand to benefit if they can transplant just the islet cells. Researchers also are studying pigs as a source of islet cells.
This month, Dr. Rilo is to begin transplants in dogs to test a new way to protect islet cells from attack by the body's immune system. If successful, related human clinical trials could begin within a year.
Also within weeks, Dr. Rilo will be participating in surgery for a man who will be getting a transplant of his own islet cells because his pancreas was damaged in a traffic accident. 'My goal isn't to treat diabetics, but to cure them,' Dr. Rilo said.
Dr. Rilo was born in Argentina. He studied medicine in Sao Paulo, Brazil, before coming to America to specialize in organ transplantation. He trained and worked for about seven years at the University of Pittsburgh, one of the nation's most active transplant centers. For the past three years, Dr. Rilo had been director of the cell transplantation lab at the University of Chicago.
Last week, Dr. Rilo was still unpacking equipment at his lab at Bio/Start, the Tristate's biotech business incubator. He designed much of the equipment he uses to harvest and analyze islet cells.
'The islet cell field is still very small, and Dr. Rilo is one of the rising stars,' said Scott King, president of Islet Sheet Medical LLC, a company that sponsors some of Dr. Rilo's research.
UC and Children's Hospital worked together to recruit Dr. Rilo. Beyond dual appointments at the UC College of Medicine and Children's, Dr. Rilo will be working closely with UC's College of Engineering.
'It's not about an individual but the fact that UC has elected to invest in a cellular transplant program,' said Dr. E. Steve Woodle, director of UC's transplantation division.
Hiring Dr. Rilo, equipping his lab and hiring several assistants is expected to cost at least $1 million. Local institutions stand to benefit from royalties any patented technology result from Dr. Rilo's work, plus the proceeds from patient care and the intangible benefits that come from building a reputation for cutting-edge care.
The stakes involved in curing diabetes -- the nation's sixth-leading cause of death -- are enormous. The national Institutes of Health estimates that Americans spend $100 billion a year on diabetes control and related care.
About one-third of all cases of blindness are linked to diabetes. So are about one-third of all kidney transplants. Vascular damage linked to diabetes is a common cause of heart disease.
The hope is that islet cell transplants could allow diabetics to live for years, if not their lives, without insulin injections and without health complications.
Doctors have proven they can work.
Studies in humans show that donor islet cells can be injected into a person's liver, where all by themselves they start producing insulin. In essence, islet cells allow the liver to take over the function of the failed pancreas.
Another advantage: islet cell transplantation is simple compared to a full-blown pancreas transplant.
The disappointment has been that the cure doesn't last. Transplanted islet cells have been easy prey for the body's immune system, Dr. Rilo said.
In the early 1990s, more than 90 percent of islet cell transplants failed within a year. As recently as 1996, two-thirds of such attempts failed. With new immune-suppressing drugs, some studies involving small numbers of patients are showing one-year success rates exceeding 90 percent.
But even that isn't good enough, Dr. Rilo said.
Islet cell cures that depend on anti-rejection drugs would only help those diabetics so sick they already need an organ transplant not the vast majority who get good control from insulin shots. That's because the risks involved in suppressing the immune system are just about as bad as the disease itself.
Among several projects Dr. Rilo is working with San Francisco-based Islet Sheet Medical on a method that would require no anti-rejection medications.
This concept calls for placing islet cells between two ultra-thin polymer screens made of material that the immune system doesn't attack.
Other research centers are looking at ways to encapsulate islet cells in microscopic polymer spheres. Scientists also are researching ways to genetically alter the islet cells themselves to make them less vulnerable to attack.
Someday, any or all these technologies will be safe and effective in humans. But how will medical science ever produce enough islets cells for a transplant.
Right now, it takes an entire pancreas, sometimes two, to harvest enough islet cells for a transplant.
If a cure relies on human islet cells, treatments would be limited because only about 7,000 people a year become organ donors when they die. There are an estimated 1 million Type 1 diabetics who want to dump their insulin needles.
To get up to mass production levels, many scientists are looking at pigs. For many years, pigs were the leading source of insulin for diabetics. Many think they can also be a source of usable islet cells.
Dr. Rilo plans to use porcine islet cells in some of his animal experiments.
Some groups vigorously oppose using animal parts in human beings, a concept the medical world calls xenotransplantation. In fact, the New York-based Committee for Responsible Transplantation wants to stop such research before it goes much further.
'We'd like to see Congress ban this stuff.' Said committee director Alix Fano. 'The risk of disease transmitted from porcine viruses to humans is a real possibility. There are so many unanswered questions that in our opinion we cannot afford to go forward with this technology.'
Medical history is laced with examples of diseases that spread from animals to humans, Ms. Fano said. The worst case in modern history may have been the swine flu virus of 1918 that killed more than 20 million people worldwide.
Scientists also have theorized that the AIDS virus started in monkeys. In recent years, Mad-cow disease rocked Europe, Ms. Fano said.
'The FDA should not be trying to minimize these risks,' Ms. Fano said. 'We've been arrogant in a lot of respects in medicine. We need to remember that we don't have all the answers here. And that xenotransplantation doesn't have to be the only approach.'
Alastair Gordon, president of the Toronto-based Islet Foundation, said fears of xenotransplantation are widely overblown.
'CRT has sounded the alarm bells while never once showing that PERV (porcine endogenous retrovirus) has ever infected a human,' Mr. Gordon said.
'There is no such thing in medicine or life as zero risk, but that's what the CRT is calling for. If we always waited for iron-clad guarantees, we'd all still be living in caves.'
Dr. Woodle, who has served on the xenotransplantation subcommittee, said the risk of triggering a new disease through transplanted animal parts appears extremely low.
'That isn't to say that there is zero risk. But that the risk should not preclude clinical trials from going forward,' Dr. Woodle said.
Dr. Rilo said porcine islet cells represent the best available way to increase the islet cell supply.
Even as the debates continue, Dr. Rilo and others are working on how to scale up and automate the islet cell harvesting process. A big part of the reason Dr. Rilo chose to move to Cincinnati was the chance work closely with the UC College of engineering on equipment designs.
Dr. Rilo has already started working on computer-controlled 'digester' equipment to replace manually controlled gear. He is working on a robotic system to handle lab samples. And he is testing a digital image processing system to see how well it can count islet cells in a fluid sample.
Such systems would be needed to mass produce islet cells. Low costs would be crucial, especially if scientists can make islet cell transplant last only a few years.
Mr. King, a diabetic himself for twenty years, predicted that islet cell transplants will become much more common within a few years for diabetics with severe complications.
'Over the years, more than $200 million has been invested into ventures to develop islet cell transplantation,' Mr. King said. 'So far, not a single product has come to market. But my personal opinion is we're getting very close. We know what success looks like.'