An experimental drug may help restore insulin production

  • The researchers investigated whether they could reprogram pancreatic stem cell-like cells into insulin-producing beta cells for a potential diabetes treatment.
  • They discovered that genes that regulate insulin expression could be reactivated using a drug previously studied for the treatment of patients with lymphoma and multiple myeloma.
  • The research results suggest a possible new treatment option for diabetic patients who depend on daily insulin injections.

According to the World Health Organization, there are about 422 million people with diabetes worldwide, with some researchers estimating this figure will reach 700 million by 2045. In the United States, approximately 1 out of 10 people had diabetes in 2018, making diabetes the number one seventh main cause of death.

There are two main types of diabetes:

  • Type 1 (formerly known as insulin-dependent or juvenile diabetes) – The body does not produce the hormone insulin or makes very little of it. This form of diabetes is more common in children and young adults.
  • Type 2 (formerly known as adult-onset diabetes) – The body does not produce enough insulin or cannot use insulin properly. It is the most common form of diabetes (90-95% of all cases) and often begins later in life.

Insulin-producing beta cells typically make up 50-70% of pancreatic islets (groups of cells in the pancreas). In both types of diabetes, there is a significant reduction in beta cells primarily due to autoimmune destruction.

People with type 1 diabetes and some people with type 2 diabetes must take insulin injections daily to survive. The alternative is whole pancreas or pancreatic islet transplantation, which is limited by the shortage of organ donors and the associated side effects of immunosuppressants.

Research on the regeneration of insulin-producing beta cells could lead to the development of a new therapy for people who depend on insulin injections.

In a recent study, the human epigenetics team at Monash University in Melbourne, Australia found that the experimental drug GSK-126 can potentially restore insulin-producing beta cells in type 1 diabetes patients by inhibiting pancreatic EZH2.

The study appears in the Nature log, Signal transduction and targeted therapythere.

The enzyme EZH2 inhibits the genes responsible for the development of insulin-producing beta cells. The researchers hypothesized that blocking EZH2 activity might restore insulin production.

Researchers examined the effect of the highly selective EZH2 inhibitor GSK-126 on specific genes related to insulin production using ex vivo human pancreatic tissue from three donors, two non-diabetic donors and one diabetic donor. type 1.

When the researchers analyzed the type 1 diabetes donor pancreas, as expected, they noted absolute destruction of beta cells. Genes that regulate beta cell development and insulin production in these pancreatic cells were “silenced.”

Researchers found that stimulating pancreatic cells with GSK-126 could restore characteristic genes responsible for the development of pancreatic progenitor cells (stem cell-like cells) into insulin-producing beta cells.

The researchers observed that GSK-126 also restored insulin gene expression in cells taken from the type 1 diabetic donor, despite the absolute destruction of beta cells. The study is the first reported example of restored insulin gene transcription and provides strong evidence for beta cell regeneration.

Professor Sam El-Osta, Ph.D., head of the Epigenetics of Human Health and Disease Laboratory at Monash University and lead author of the study, described this method of restoring insulin production as “fast and cost effective”.

“Our preliminary studies show vital insulin expression as early as 2 days of drug therapy compared to 3-4 months with alternative approaches using human embryonic stem cells,” Dr. El-Osta said. DTM.

By avoiding the use of embryonic stem cells, the study authors also avoided the ethical concerns typically associated with such techniques. Another benefit of this potential diabetes treatment is that it is “less vulnerable to the risks associated with organ or islet transplantation,” he added.

Commenting on the limitations of their study, the researchers noted that they used cells from a single type 1 diabetes donor. Further studies are needed to determine if the approach is successful in a larger type 1 diabetes population. wide.

Autoimmune attacks on insulin-producing beta cells also present another obstacle to the development of a new therapy, according to Dr. Matthias von Herrath, professor and founder of the Type 1 Diabetes Center at the La Jolla Institute of Immunology. in the USA.

“In type 1 diabetes (and some cases of type 2 diabetes), there is a fairly strong (auto)immune reactivity towards islets and insulin-producing beta cells, [which] will not be avoided by doing more. So, although this is an interesting progress, we would still have to deal with the reduction of this autoim[m]a reaction (ideally w[i]without systemic immunosuppression of patients), which [is] not an easy task. said Dr. Von Herrath.

While this potential new diabetes treatment offers hope for people with type 1 diabetes, it’s “not ideally targeted” at type 2 diabetes, according to Dr. John Buse, Ph.D., director from the Diabetes Center at the University of North Carolina. . “In the most common cases [T]type 2 diabetes, usually the biggest problem is that the insulin doesn’t work very well,” Dr Buse said. DTM.

When asked how soon this treatment option could be made available to the public, Dr Buse said: “With a lot of focus, funding and luck, human drug therapy based on early demonstration of the benefits, as in this article, usually takes 7-10 years. . And in this case, the path to drug development is complicated by the need to get the cells out of the body and into the lab, and then get them back to the patient.


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