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Two novel therapeutic candidates for the treatment and reversal of various morbidities associated with diabetes mellitus, obesity, and gastrointestinal motility disorders.

Description:

BACKGROUND

According to data from the World Health Organization, there are over 425 million diabetic patients in the world, and that number has been rapidly increasing as the prevalence of obesity also increases. Obesity and diabetes are closely interconnected as 90% of diabetics are also obese. People with type 1 diabetes (T1D) don’t produce insulin while people with type 2 diabetes (T2D) don’t respond to insulin. T2D accounts for up to 95% of all diagnosed cases of diabetes. T2D is a complex and heterogeneous polygenic disease, known as adult diabetes which mainly occurs in adults over 40 years old. Interestingly, about half of diabetic patients also have gastrointestinal (GI) complications, including gastroparesis (delayed gastric emptying). It is known that an abnormally high blood glucose level (hyperglycemia), a hallmark sign of diabetes, leads to gastroparesis.

Due to the complexity and induction mechanisms of both T1D and T2D, successful prevention and long-term treatments have been difficult to develop.    

DESCRIPTION

Researchers at the University of Nevada, Reno have discovered two novel microRNA (miRNA) therapeutic candidates that have been shown to have profound and prolonged effects in the treatment and prevention of T1D, T2D, obesity, fatty liver disease, hyperlipidemia, inflammation, gastroparesis, and constipation.

ADVANTAGES AND THERAPEUTIC EFFECTS
 

  1. Both candidates lower blood glucose to normal levels in obese and diabetic mice fed a high-fat and high-sucrose diet (HFHSD). 
     
  2. Both candidates lower body weight for extended time periods in obese and diabetic mice fed a HFHSD. They lowered body weight by 50% and 5%, respectively and mice that lost 50% body weight remained healthy for up to 5 months without regaining weight.
     
  3. One candidate dramatically reverses fatty, fibrous, inflamed, and damaged liver conditions. Healthy liver functions were restored with a single injection in obese and diabetic mice fed a HFHSD.
     
  4. One candidate improves heart function in obese and diabetic mice fed a HFHSD.
     
  5. One candidate restores healthy cholesterol levels in obese and diabetic mice fed a HFHSD. It increased LDL (bad cholesterol) but increased HDL (good cholesterol).
     
  6. Both reduces inflammation in obese and diabetic mice fed a HFHSD.
     
  7. Both improve gastrointestinal (GI) function [total GI transit, gastric emptying (gastroparesis), and colon transit (constipation)] in obese and diabetic mice fed a HFHSD.
     
  8. These two novel therapeutic candidates may be used to treat T1D and T2D. One candidate increases insulin production while the other candidate increases insulin sensitivity.
     
  9. Injections of these novel candidates in healthy mice do not decrease their body weight or blood glucose beyond normal levels (no underweight or low blood glucose risk).
     
  10.  These novel candidates prevent the development of all aforementioned diseases in mice fed a HFHSD.
     
  11.  These novel candidates induce proliferation of adult stem cells or progenitor cells in the damaged tissue of obesity and diabetes and enhance regeneration of the damaged cells.
     
  12. Both of these novel therapeutic candidates were shown to have a more profound effect in lowering blood glucose in HFHSD induced obese and diabetic mice than the four most commonly prescribed antidiabetic medications as well as an investigational miRNA which just finished phase 2 in patients with diabetes and non-alcohol fatty liver disease.  In addition, both candidates were shown to have a more profound effect in improving GI function (gastroparesis and constipation) in HFHSD induced obese and diabetic mice than a commonly prescribed prokinetic medication.

 

RELATED INFORMATION

US Provisional Application No. 62/837,988

US Provisional Application No. 62/964,382

UNR18-017 & UNR20-023                                   

Patent Information:
For Information, Contact:
Cara Baird
Licensing Associate
University of Nevada, Reno
carab@unr.edu
Inventors:
Seungil Ro
Keywords: