Dashed Hopes of A Miracle Cure For Diabetes: Making Progress Through Retractions

Credit: Pixabay
Credit: Pixabay

Imagine your typical middle aged working professional. Let us call her Tara. With an increasing sedentary life style and age, she tries to control her eating patterns. She tries to stay far away from the food she used to like as a child. She accounts for inactivity and erratic lifestyle by strict diet control. Her doctor advises Tara to keep her blood glucose target range between 6 to 12mmol/L. As an adult, Tara realizes the strict diet choices that she must make to feel and look healthy.

But what if Tara were not an adult but a 6-year-old? What if this strict lifestyle is not a choice and rather a necessity to prevent slipping into a diabetic coma? Every year thousands of children adopt rigorous lifestyles like Tara’s just to stay alive. They all share a common condition – Type I diabetes.

Type I diabetes is a chronic condition in which the body does not produce insulin. Patients with Type I diabetes need to monitor their sugar levels throughout the day and administer insulin at regular intervals. Patients are insulin-dependent throughout their lives.

Epidemiological evidence shows that Type I diabetes is diagnosed early in life. Families raising kids with Type I diabetes follow strict treatment regimens that are often at odds with the nature of activities that children seek and enjoy. In addition, studies have reported cognitive impairment in patients with Type I diabetes. Currently there are no treatment options other than constant blood glucose monitoring and insulin shots. Living with Type I diabetes takes its toll on families as they cope with their children as well as expensive treatment regimens. Unlike many such parents, Doug Melton decided to become a part of the solution. Melton, raising two children with Type I diabetes, decided to use his training as a molecular biologist to understand and identify therapeutics.

Type I diabetes is an autoimmune disease. Specifically, an autoimmune reaction kills the insulin-producing beta cells of the pancreas. Melton’s 30 personnel lab and his startup, Semma therapeutics started working on using embryonic stem cells to make new beta cells that could potentially allow patients to live lives independent of insulin pumps and glucose monitors. In his battle against Type I diabetes, Melton has also become one of the most lauded academic researchers in his field.

In 2013, Douglas.A. Melton’s lab at Harvard published a study on Betatrophin, a hormone found in the liver. The paper published in Cell, reported the hormone’s action to increase the number of insulin-producing beta cells in mice and a potentially new way to treat patients.

The very next year, an independent group of researchers from institutions across the US published a report refuting the study. In their study, Betatrophin was found to have no effect on regulation of blood glucose levels or beta cell numbers. In 2016, Melton and researchers from Baylor College of Medicine and the Joslin Diabetes center resolved the issue by publishing a strong refutation of their original idea. In a retraction notice published this month, Melton and his co-authors decided to retract the original paper as their initial conclusion could not be supported and reproduced by multiple independent studies by researchers across US.

Speaking to STAT News, Melton says, “It’s a disappointment, like any retraction, but the gradual teardown of the betatrophin hypothesis illustrates “how scientists can work together when they disagree, and come together to move the field forward.

“The history of science shows it is not a linear path,” he added.

As any molecular biologist, will tell you, contradicting results and frustrating outcomes are a way of life in science. It is common for post-doctoral fellows and graduate students to work on a lead for three months before realizing that it is a dead end.

It is perhaps ideal that a man familiar with these pitfalls is leading the effort to find a cure for Type I diabetes. In 2016, the Melton lab could demonstrate the use of transplanted human beta cells to maintain glucose levels in mice based on 15 years of research.

Melton’s startup Semma therapeutics is also developing protocols to make the various cells of the pancreas from embryonic stem cells. Despite numerous advances, scientists are no closer to a cure.

Until researchers find a cure, children including Melton’s own kids must stay insulin shot dependent.

Source: STAT news