Researchers aim to 'reverse' juvenile diabetes

By Wai Lang Chu

- Last updated on GMT

Related tags: Dendritic cells, Insulin, Immune system, Diabetes

New diabetes trials scheduled to start this spring have been
heralded as groundbreaking as researchers aim to reverse juvenile
diabetes of which numbers have been steadily on the rise in
developed nations.

Type 1 diabetes is known as insulin-dependent diabetes mellitus (IDDM) or juvenile-onset diabetes. While type 2 diabetes typically strikes adults, the National Institutes of Health (NIH) reports that more than 1 million children and teenagers (age 19 and younger) in the US have type 1 diabetes.

According to the NIH, 5 per cent to 10 per cent of diagnosed diabetes cases in the US are type 1 diabetes.

Researchers from Pittsburgh's Children's Hospital, Pittsburgh University and Pittsburgh Medical Center observed marked amelioration of diabetes in a mouse model by the novel treatment strategy involving specific modification of the animal's own dendritic cells, thereby reversing diabetes in animal studies.

Massimo Trucco and Nick Giannoukakis found by removing dendritic cells from the blood during a two- to four-hour procedure, some 20 million dendritic cells could be harvested.

Dendritic cells are cells found in the bloodstream and normally function as one of nature's most efficient immune function cells. The cells identify foreign substances such as cancer cells, process these foreign substances, and then jumpstart the immune response by bringing these foreign substances to the attention of T cells.

Once harvested, researchers then combine the dendritic cells with specific blockers of molecules, known as CD40, CD80 and CD86, all of which can be synthesised in a laboratory.

This treatment strategy was found to inhibit the interaction and destructive effect of T cells on the insulin-producing beta cells of the pancreas, a process that is known to be a critical part of how diabetes occurs.

Subcutaneous injection of dendritic cells into the abdominal/pelvic area near the pancreas and lymph nodes, blocks the T cells as they travel to the pancreas to destroy beta cells.

"We did this in mice, giving them six injections over the course of several weeks. The injections interrupted the T cell and beta cell interaction, allowing the beta cells in the pancreas to regenerate. This enabled the pancreas of the mice to begin producing insulin again,"​ said Dr. Trucco.

"The injections proved capable of stopping this vicious cycle, and through this process curing type 1 diabetes in a mouse."

Until now, scientists weren't sure why the immune system attacks the beta cells, but the result is that the body stops producing insulin. When that happens, glucose builds up in the blood, but the body's cells starve to death.

"We are very excited to begin the clinical trials and see if this process will work in patients with type 1 diabetes,"​ he said.

"A type 1 diabetes diagnosis can be devastating for children and their families. We hope this trial will have results that are life-altering for patients who suffer from this disease."

The US Food and Drug Administration (FDA) approved the start of a clinical trial to evaluate the safety and feasibility of the treatment (Phase 1 trial).

The trial is expected to begin sometime this spring and will include at least 15 patients over the age of 18, with type 1 diabetes.

In addition, Dr. Trucco and his team want to combine the dendritic cells with small portions (i.e. peptides) of insulin. Dr. Trucco believes that adding small doses of insulin to the dendritic cells will help guide the dendritic cells directly to the T cells.

Adding the insulin ensures the dendritic cells are used specifically to block the T cell destruction of the beta cells, and not otherwise interrupt a person's immunity.

In other words, the dendritic cells are led directly to the target, the T cells that are causing the malfunction of the pancreas, and not to another part of the body.

Type 1 diabetes is regarded as an autoimmune disease because a person's immune system attacks and destroys the beta cells in the pancreas that produce insulin.

Symptoms of type 1 diabetes usually develop over a short period of time and include increased thirst, frequent urination, constant hunger, weight loss, blurred vision and extreme fatigue.

People with type 1 diabetes require numerous daily injections of insulin to survive

Related topics: Preclinical Research

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