Using RNA to target islet beta cells and hopefully get rid of insulin!

News

Using RNA to target islet beta cells and hopefully get rid of insulin!

The ability to detect and target beta cells in vivo could dramatically refine how diabetes is studied and treated. However, the lack of specific probes still hinders the precise characterization of human beta cell populations and the delivery of therapeutics in clinical settings.

Recent studies have designed RNA molecules to target pancreatic beta cells, creating new opportunities for targeted therapy that encourages beta cell proliferation or locally suppresses immunity without causing systemic side effects. And adequate treatment is expected to reverse diabetes and get rid of insulin.

Researchers at the University of Miami Miller School of Medicine have engineered RNA molecules that home to human pancreatic beta cells , the cells that produce insulin and are destroyed in people with type 1 and type 2 diabetes.

This targeted approach could help researchers study how these diseases progress and provide new ways to deliver treatments. The study, ” RNA aptamers specific for transmembrane p24 trafficking protein 6 and Clusterin for the targeted delivery of imaging reagents and RNA therapeutics to human beta cells ,” was published April 5 in Nature Communications .

Using RNA to target islet beta cells and hopefully get rid of insulin! https://www.nature.com/articles/s41467-022-29377-3

Associate Professor Paolo Serafini , Ph.D., the paper’s senior author, said: “We have created a tool to specifically deliver an agent to human beta cells. This gives us new capabilities. We can use PET or CT scans to count beta cells and By measuring disease progression, we can deliver treatments directly to beta cells without causing side effects elsewhere in the body. “

Type 1 diabetes is caused by an autoimmune response that targets pancreatic beta cells. Over time, the immune system destroys these key insulin-producing cells, and the body can no longer control glucose levels, leading to severe blood vessel and organ damage. While insulin can be an effective treatment, it is not a cure.

Type 2 diabetes progresses differently. Cells develop insulin resistance, which means beta cells have to work harder to produce more hormones. Eventually, beta cells die from exhaustion, again dysregulating glucose metabolism.

Researchers studying these diseases have never been able to get a good census of how many beta cells are alive in the pancreas at any given moment. They rely on surrogate indicators, such as glucose levels, which provide only limited information about how these conditions evolve.

Scientists trying to develop treatments are often hampered by the toxicity and other side effects associated with systemic treatments— they want a system that can deliver treatments directly to beta cells.

“If we treat patients with non-targeted drugs that encourage beta cell proliferation, those drugs affect many other tissues and can lead to cancer,” Dr. Serafini said. “Similarly, if we were trying to protect beta cells from an autoimmune response, non-targeted therapy would cause systemic immunosuppression, leaving patients vulnerable to pathogens that again lead to cancer.”

Dr. Serafini and colleagues solved these problems by creating two distinct RNA aptamers. In turn, scientists can attach additional molecules to illuminate beta cells (for imaging) or treat disease.

This will give scientists new opportunities to create targeted therapies that encourage beta cell proliferation or suppress immunity locally without causing systemic side effects. Furthermore, the ability to precisely measure beta cell mass will improve future studies.

Dr Serafini said: “It will be cheaper and easier to conduct clinical trials because we will be able to see in real time what is actually happening in the beta cells . In the past, we had to measure glucose or insulin to infer what was going on in the pancreas. Now, we can actually see it.”

Researchers have already begun testing potential treatment options. They are conducting preclinical research in collaboration with WiNK Therapeutics and the Juvenile Diabetes Research Foundation (JDRF), hoping to advance these approaches into human trials in the coming years.

“We are working with JDRF on follow-up studies to block the autoimmune response and encourage beta cell proliferation, ” said Dr. Serafini. ” Theoretically, with adequate treatment, we could increase beta cell mass to reverse diabetes and also protect beta cells from autoimmunity so that people no longer need insulin. “