Mount Sinai Discovers Novel Drug Combo Helps Replicate Insulin-Producing Beta Cells

Source: Mount Sinai Health System

Diabetes

About 463 million adults worldwide are estimated to be living with diabetes, according to the International Diabetes Federation’s Diabetes Atlas 2019—nearly 6% of the global population. By 2045, this number is projected to rise to 700 million patients globally

According to the CDC, more than 30 million people in the US have diabetes, and one-quarter of these people don’t know they have it. Over one-third of US adults—84 million people—has prediabetes, with blood sugar levels higher than normal but as yet below the threshold of a diabetes diagnosis. The CDC estimates that 90% of people with prediabetes don’t know they have it.

Diabetes occurs when there is insufficient insulin being produced by cells in the pancreas called ? cells, or beta cells, or when there are not enough beta cells present.

Researchers at Mount Sinai Take an Important Step Toward Restoring the Body’s Ability to Produce Insulin

Researchers at the Icahn School of Medicine at Mount Sinai have discovered a novel combination of two classes of drugs that cause adult human beta cells to proliferate at 5% to 6% per day, the highest rate ever observed without harming most other cells in the body.

We are very excited about this new drug combination because for the first time ever, we are able to see rates of human beta cell replication that are sufficient to replenish beta cell mass in humans with diabetes.

– Andrew Stewart, MD, Director of the Mount Sinai Diabetes, Obesity, and Metabolism Institute and lead author of the study.

Researchers combined two classes of drugs:

• Dual Specificity Tyrosine Phosphorylation Regulated Kinase 1A (DYRK1A) inhibitors, which are known to cause beta cells to proliferate
• Glucagon-like peptide 1 receptor (GLP1R) agonists, several of which have been FDA-approved and are widely prescribed for type 2 diabetes, including:
  • Ozempic (semaglutide) and Victoza/Saxenda (liraglutide) — Novo Nordisk
  • Trulicity (dulaglutiade) — Eli Lilly
  • Adlyxin (lixisenatide) — Sanofi
  • Byetta/Bydureon (exenatide) — AstraZeneca

These approved GLP1R agonists demonstrate reductions in A1C, body weight, lipids and blood pressure.

The researchers showed—using beta cells from healthy adults and from adults type 2 diabetes, both in tissue culture dishes and in beta cells transplanted into mice—that combining a DYRK1A inhibitor with any of the many GLP1R agonist drugs currently on the market for diabetes yields high rates of human beta cell replication, and does so without harming most other cells in the body.

The beauty here is that the combination of DYRK1A inhibitors with GLP1R agonists achieves the highest rate of human beta cell replication possible, and does so in a highly specific way. This is an important advance in the field of diabetes because we may have found a way to convert a widely used class of diabetes drugs into a potent human beta cell regenerative treatment for all forms of diabetes.

– Courtney Ackeifi, PhD, Postdoctoral fellow, Stewart Laboratory, whose PhD thesis at Icahn School of Medicine was the inspiration for the study.

The study is entitled, “GLP-1 receptor agonists synergize with DYRK1A inhibitors to potentiate functional human ? cell regeneration,” and was published online today in Science Translational Medicine (sciencemag.org/content/12/530/eaaw9996).

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Edward Kim is Managing Editor of Equities.com.

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Sources: Equities News