Tuesday, December 24, 2013

Targeting Diabetes, From The Negev

When Andy David’s nine-year-old daughter was diagnosed with Type 1 diabetes, the Israeli diplomat used his medical background to search for an unconventional treatment that would spare her from daily doses of insulin.
David, who is currently Israel’s consul general for the Pacific Northwest United States, soon learned about groundbreaking work at Ben-Gurion University in the Negev that shows great promise for kids in the early stages of Type 1 diagnosis.
The child (he prefers not to name her for security reasons) underwent eight weeks of transfusions of Alpha 1 Antitrypsin, an anti-inflammatory drug generally used to treat emphysema.
“That was two and a half-years ago, and she has not had to have insulin,” said David, who is a non-practicing dentist and also has a degree in Medical Science fromHebrew University in Jerusalem.
He notes that his daughter still needs to have her sugar levels regularly monitored and that her treatment -– she is one of several dozen to receive it so far – is still very experimental. “It’s not something you will find mainstream,” he says.
The success of the treatment was in receiving it soon after symptoms appeared, when the body still has a large number of insulin producing cells that could be boosted by the drug.
David’s younger child, diagnosed sooner, was not a candidate for the therapy and requires insulin shots.
He praised the researchers at Ben-Gurion for their groundbreaking work. “Their goal is not to manage diabetes but to eliminate it,” he said.
Several years after it was discovered, Alpha 1 is showing new promise in the war against diabetes, which may affect as many as 550 million people, one in 10 globally, by 2030 if current trends continue, the International Diabetes Foundation warns.
“There are new areas that have become relevant for our therapy,” said Dr. Eli Lewis of Ben-Gurion University, above, in a recent interview in New York. He was in town to present new findings to peers and other interested parties.
The approach may soon allow for treatment of the more prevalent Type 2 diabetes, commonly developed in adulthood, and for other diseases, including other autoimmune disorders, said Lewis.
The treatment focuses on preserving healthy pancreatic cells in charge of the natural production of insulin. The results of clinical trials have been encouraging, and it has been proven to “cure” laboratory mice in whom diabetes has been induced, as published by his group and by independent related research groups.
Doctors commonly treat Type 1, previously known as juvenile diabetes, with a complex daily regimen of insulin injections to boost the supply of the hormone that regulates blood glucose.
A less common treatment, when there are too few cells to produce healthy levels of insulin, is to transplant healthy islets – naturally occurring clusters of 5,000 or more cells  -- to the patient with Type 1 diabetes. About 90 percent of those cells produce insulin. But as in any transplant, the body’s immune system attacks the foreign cells and rejection hampers efficiency, requiring immunosuppressive drugs.  Such islet transplant patients, since the year 2000, have typically returned to insulin injection within 5 years after the procedure.
Researchers at Ben-Gurion’s Clinical Islet Laboratory have found a way to use Alpha 1 to aid the graft recipient in accepting the transplant. The drug is already approved by the Food and Drug Administration, allowing a fast-track to human clinical trials in the U.S., where an estimated three million people suffer from Type 1 diabetes.
Unlike Type 1 diabetes, in which the body does not produce enough insulin, Type 2 diabetes, commonly associated with diet and lifestyle factors (with a likely genetic predisposition) occurs when the insulin produced is not effective because of other factors in the body. Adding hope for such patients, Lewis says his team is now able to preserve islets that previously fell victim to high glucose, fatty acids and drug toxicity.
While initial research has focused on transplants of islets from human donors, Lewis now says his team is was able to finally also cross the barrier to the more difficult rejection process, such that attacks non-human tissue.
Lewis said pig cells are generally used because of the scarcity of human donors, and because the cells are most compatible with humans. However, “transplant from one species to another is a huge barrier. Cells from a different species evoke an immune response that are harder to block."
Alpha 1 is a protein that exists already in the body and its production increases when we are sick. Administering proper doses of the drug boosts the ability of the transplanted cells to survive long-term by inhibiting inflammation and minimizing tissue injury.
Clinical trials so far have shown that within 8 to 12 weeks patients can end the Alpha 1 therapy and maintain proper glucose levels without insulin for more than two years.
“We figured, let’s use this molecule that the body is making anyway when it needs to recover tissues and see if we can hit Type 1 diabetes at the most dynamic point, which is soon after diagnosis,” says Lewis. “Those are the trials we did for two years that are just completed and we are writing them up. The outcomes are pretty astounding. Within two or three years … no antibodies [fighting the islets] and other parameters in an impressive volume of participants.”
Because cell inflammation promotes the spread of other serious illnesses, the Alpha 1 therapy may prove effective in fighting unhealthy inflammatory conditions outside Type 1 diabetes.
Lewis said that diabetes rates in Israel are similar to those of western nations because of similar diets and lifestyle. He cautions that the high-fat, high-sugar diet that precipitates Type 2 diabetes is especially dangerous because it represents a double amount of stress to beta cells in poorly controlled Type 2 diabetes.
 “The body is designed to handle one or the other,” he said. “But the combination is something the islets can’t handle.” He further warns that even when people resolve to increase exercise and improve their diet, it won’t necessarily reverse the damage. “It becomes imprinted in the DNA,” he said  “The long-term implications might start to turn up even if you change your lifestyle, so early prevention and control are absolutely essential.”
For more information, contact Kevin Leopold, 
executive director, American Associates, Ben-Gurion University of Greater New York Region
: kleopold@aabgu.org


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