Cell Mates

Dr. Bashoo Naziruddin and Dr. Robert Kane

When professional racing cyclist Justin McQuerry sweeps past crowds of cheering fans, few would suspect that he and his teammates have much more in common than a passion for winning — they are all type 1 diabetics.

McQuerry and his fellow racers are members of Team Novo Nordisk, a global all-diabetes sports team of cyclists, triathletes and runners. They ride to make a point: type 1 diabetes may be a potentially devastating disease, but it doesn’t have to hold anyone back.

“I was diagnosed at age 2 years, 9 months, so I really don’t know much else other than living with diabetes,” McQuerry explains. “Growing up I ne ver really thought much of managing m y diabetes; it was just a part of my daily routine.”

Type 1 diabetes occurs when “beta cells” in the pancreas come under assault fr om the body’s autoimmune system and stop making insulin, a hormone crucial to regulation of sugar in the body. As in McQuerr y’s case, the disease usually strikes in early childhood.

New drugs, insulin pumps and other advancements have made it easier and less painful for diabetics to cope with their disease, improving their quality of life while extending their life spans by decades. But unfortunately, a cure remains out of reach.

Or does it?

Transplantation of an entire pancreas or of the pancreatic “islets” that contain beta cells has been practiced for over 40 years with results that have been dramatic at times. But widespread and routine use of the procedure faces several obstacles. First, there are very few viable organs available for transplantation, and islets themselves are very difficult to condition for transplantation. Only a few institutions have the necessary infrastructure to attempt it. Even when islets can be transplanted, the same autoimmune process that caused the patient’s diabetes can destroy the new islets, sometimes in only a matter of hours. Inflammation of the islets adds to the problem, as does the danger posed by the clots formed when blood cells clump together on the islets. Each of these challenges is formidable.

“It’s not a new issue; people ha ve described the problem for a long time and ar e using several approaches to protect the islets, to minimize the damage,” says Dr. Bashoo Naziruddin, director of the Baylor Research Institute’s cGMP Islet Cell Processing Laboratory in Dallas. Naziruddin, a transplant immunologist, has spent decades studying islets and working to improve the transplantation success rate. For the last several years he has been aided by a steady stream of top-notch graduate students in chemistry and biochemistry, many of whom come to his lab from Baylor University’s Institute of Biomedical Studies in Waco. Baylor chemistry professor Dr. Robert Kane is the institute’s director. Several years ago one of Kane’s students was developing ways to attach molecules to the exterior of a cell. Naziruddin heard about the project.

“I told Dr. Kane that pancreatic islets would be a good cell model to use because they just make insulin. It’s easy to track down where the insulin is secreted, how much is secreted; so after any modification you do it’s easy to check the biological function to see the effect.” That turned out to be very good advice, and the two soon began to evaluate techniques to give the islets a kind of Harry Potteresque “invisibility cloak” that keeps them from being seen as a threat by the body’s immune system.

“That’s the goal, to ‘camouflage’ the islets so they are hidden from the blood cells that attack them,” Naziruddin explains. “I really had no expertise in surface modification of islets, so I reached out to Dr. Kane.”

“Right,” Kane continues. “We started looking at practical approaches to attaching molecules in a way the islets could tolerate them. We established fairly quickly that we could do the chemistry; then we had to decide what to attach, what molecules would hide the islets.”

Although an ambitious project, early results are encouraging and the two institutions bring an array of capabilities to bear on the problem, making Kane confident.

“My lab is very good at looking at things at the atomic scale. We do organic chemistry, we look at what bonds are formed, we know how to manipulate things on that scale. Dr. Naziruddin is very good at manipulating things on the cellular and organ scales, and he is in a clinical environment as well. So our work goes all the way from the atomic scale up to the human scale, “ he says.

“The ‘bench-to-bedside’ approach is what we call it,” Naziruddin adds. “We not only have a major transplant center, we also have the ability to do basic research. We have over 600 human trials going on right now, so anything we find in the lab could be translated into a clinical setting very quickly.”

That would suit McQuerry just fine.

“A cure would literally be life-changing,” he says, adding, “but as a cyclist and an endurance athlete, I will always be dedicated to good nutrition and living a healthy lifestyle.”