By Maayan Jaffe/JNS.org
While methods of insulin administration have improved, and modes of measuring how much insulin to give are far superior to those of the 1920s, when insulin was discovered, there have been no major advancements toward a cure for Type 1 diabetes for almost a century.
Until now, Dr. Eli Lewis believes.
“Tissue damage actually plays a role in Type 1 diabetes… but it is often overlooked and under-studied,” Lewis—a world-renowned expert on autoimmune disease and the director of the Clinical Islet Laboratory of the Department of Clinical Biochemistry & Pharmacology at Ben-Gurion University (BGU)—told JNS.org. “There was at least one stone that was left unturned.”
In 2003, Lewis began his research into the role of inflammation in injured islets, tiny clusters of insulin-producing cells scattered throughout the pancreas. And during that time he discovered that Alpha 1 Antitrypsin (AAT), an anti-inflammatory drug based on a natural protein our bodies produce each day and generally used to treat emphysema, not only shows promise for reducing insulin dependence but in some cases can actually cure a person of Type 1 diabetes.
Diabetes plagues 25.8 million Americans of all ages, and about 5 percent of that group has Type 1 diabetes, according to the National Diabetes Information Clearinghouse. All Type 1 diabetics require insulin treatment.
The hormone insulin, produced by clusters of cells found on islets that reside in the pancreas, enables the body to remove glucose (sugar) from the blood into storage locations such as liver and muscle. These cells are the targets of an autoimmune response in Type 1 diabetes. When the cells become inflamed and ultimately malfunction, insulin can no longer be produced. In a healthy individual, the body naturally produces systemic AAT in the liver that helps repair tissue and reduces inflammation. It was recently established that AAT, although present in patients with Type 1 diabetes, does not function in its glycated form.
In three recent clinical trials that took place at BGU, the Barbara Davis Center for Childhood Diabetes at the University of Colorado School of Medicine, and the Joslin Diabetes Center (affiliated with Harvard Medical School), recently diagnosed patients received injections of functioning AAT in the form of a liquid slow-drip infusion. They basically regained the ability to fight inflammation and protect damaged cells from aberrant immune responses. Within eight to 12 weeks AAT therapy was withdrawn, and in several patients proper glucose levels were controlled without the need for insulin injections for more than two years.
Since AAT was already approved by the Food and Drug Administration (FDA), it received fast-track approval into human clinical trials in the U.S., Lewis said, noting it still will take at least another two years for AAT to receive FDA approval as an on-label treatment for Type 1 diabetes. But some physicians have been prescribing it in the meantime as an off-label treatment.
Dana Heffernan’s son Zach, 11, received AAT treatment from his doctor in San Antonio, Texas. Heffernan said her son was diagnosed on Nov. 12, 2013 and received his first treatment in mid-December.
“He went from approximately 10 units of insulin per day [70 units per week] down to two units per week. So that is pretty significant. Will he ever be off insulin completely? That is my hope, but we will have to see,” Heffernan said.
In another public case, which Lewis discussed, the Consul General of Israel to the Pacific Northwest, Andy David, accessed AAT for use in treating his 9-year-old daughter. She underwent once-a-week slow-drip infusions of AAT for 8 weeks. That was close to three years ago, and she has not had to have insulin since.
The treatment, however, may not be effective for all patients. Dr. Peter A. Gottlieb, professor of pediatrics and medicine at the Davis Center, led the Colorado clinical trial. He said the treatment was promising for about one-third of those who received AAT, but was less effective or even ineffective in others. He attributes this to multiple factors, including how long the person has had the disease and how much of the AAT was administered. He said another set of clinical trials is underway using larger doses. Lewis said in all trials, if one has been diagnosed with Type 1 for more than six months “the benefits are minimal.”
Gottlieb also noted that AAT is a “pretty expensive” drug, since it is extracted from human plasma. This could prove a barrier. Omni Pharmaceuticals is working on a second-generation drug, Gottlieb said, which could prove as effective and also reduce the price tag for treatment. Lewis said large-scale production of AAT would also allow for researchers to improve the drug’s functionality.
The results of the most recent clinical trials will be published this March in The Journal of Clinical Endocrinology and Metabolism.
Lewis noted that researchers are still unclear as to why one gets Type 1 diabetes. While genetic factors certainly play a role, more recent studies have indicated that the disease could also be linked to stress/trauma (even psychological trauma), or could be viral. His lab has also found a way to use AAT to aid in islet transplant survival and is working on how the drug might prove useful for the treatment of Type 2 diabetes, commonly associated with diet and lifestyle factors. He cited a Swedish study that found half of patients with Type 2 diabetes to have decreased levels of circulating AAT.
Lewis will be in the U.S. in late March and early April to talk about his findings and look for additional medical research partners in the U.S. His visits will include major cities, such as San Antonio, Los Angeles, Washington, D.C., Baltimore, Philadelphia, and New York. For more information about these visits, contact your local chapter of American Associates of Ben-Gurion University of the Negev (http://www.aabgu.org/).
If one is interested in being a part of a clinical trial, ongoing studies can be found at clinicaltrials.gov. Type “diabetes” and “Antitrypsin” into the search bar.
“We’re not out of the woods,” said Lewis. “More than ever, there is promise. … Our team at BGU is working on this relentlessly, and we hope the upcoming visit to the US will represent a shift-in-gear to a more rapid advance.”
Maayan Jaffe is a freelance writer in Overland Park, Kan. To reach Maayan email email@example.com.
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Correction: The initial version of this story stated that Type 1 diabetes plagues 25.8 percent of Americans. The correct figure is that about 5 percent of the 25.8 million diabetics in America have Type 1 diabetes.