Houston, Texas, USA : Millions of people take insulin every day to treat their diabetes. But diabetes is not the only disease on which insulin has an effect, it appears. Chronic bowel inflammation can be treated effectively by injecting insulin into the rectum, it appears from a new study, where researchers have tested the treatment on mice. The study is a collaboration between departments at the University of Copenhagen and Roskilde University.
‘Our new treatment with insulin on mice shows great potential against chronic bowel inflammation in humans like Colitis Ulcerosa, which causes a lot of people great discomfort. Existing treatments attack the bowel’s immune system, dampening it; instead our method strengthens the bowel cells’ own defence. It appears to work equally well, and it can probably be used in combination with existing treatments’, says Jørgen Olsen, co-inventor of the treatment and professor at the Department of Cellular and Molecular Medicine, University of Copenhagen.
The new study has just been published in the scientific Journal of Crohn’s and Colitis, and it has examined the effect of the treatment in a series of tests on mice with chronic colitis of the type Colitis Ulcerosa, among others, from which 20.000 Danes suffer. The cause of these bowel disorders is unknown, but they cause patients great discomfort and can involve bloody diarrhoea, anaemia, stomach ache and weight loss.
Strengthened Defence and Weakened Attack
The researchers have studied the effect of the insulin treatment in various ways. First, they have shown that the amount of inflammation, expressed as the level of the marker Cox2, drops by 50 per cent compared to the saltwater control treatment. That is more or less the same effect shown in tests on mice prior to the launch of the existing treatment in the market.
Second, the researchers have measured the body weight of the mice – we know that people suffering from colitis typically lose a lot of weight because they do not eat much. As this marker is relatively crude, some studies of the existing treatment have shown no effect at all. However, using the new insulin treatment the mice lose 15-20 per cent less weight than the control group, and following treatment they gain weight 50 per cent faster, which is an important sign of health.
The insulin works because it activates a gene inside the bowel cells, which, according to other studies, has an antioxidant effect and thus may be able to protect the bowel cells from inflammation. This makes the new treatment different from existing medication, which instead of strengthening the bowel’s defence weakens the immune system’s attack on the bowel. And therefore the researchers hope the new treatment can be combined with the existing.
Hope for Fast Authorisation
Based on the positive results the researchers have now set up a company that will test the treatment in clinical trials on humans and hopefully eventually make the technology available to patients.
Together with the researchers, the University of Copenhagen has applied for a patent on the treatment method. The patent application has been published and will be processed by the European and US patent authorities. The researchers’ company and the University of Copenhagen are currently negotiating a licence agreement on commercial exploitation of the patent.
According to Professor Jørgen Olsen the researchers should, using traditional research funds, be able to initiate the so-called phase one trials, which are the first safety tests performed on humans closely monitored by healthcare personnel.
At the same time, the researchers are currently looking for investors willing to help them once they are ready for phases two and three, as they expect the authorisation process to be swift compared to brand new drugs, because injection in the rectum with existing drugs is a method that is already being used by these bowel patients, and because insulin is already a widely approved drug for diabetes patients.
The study is funded by the Lundbeck Foundation, among others.
Video : Diabetes is not the only disease on which insulin has an effect, it appears. In a new study that involved tests on mice researchers from the University of Copenhagen, among others, have discovered a new method for treating chronic colitis with regular insulin. The researchers have set up a company with a view to testing the treatment and hopefully making it available to patients.
Video credit : University of Copenhagen, Faculty of Health and Medical Sciences
In a separate study, researchers treated inflammatory bowel disorder by delivering microRNAs
Citation: Mohammad Yassin et al, Rectal insulin instillation inhibits inflammation and tumor development in chemically-induced colitis, Journal of Crohn’s and Colitis. DOI: 10.1093/ecco-jcc/jjy112
Treating inflammatory bowel disorder by delivering microRNAs
Inflammatory bowel disease (IBD), such as Crohn’s disease and ulcerative colitis, are chronic inflammatory diseases of unknown cause, and the number of IBD patients is on the rise.
Various inflammatory cytokines, including TNF-α and interleukin-6 (IL6), damage the intestinal wall, causing IBD. Thus, the cytokine signaling pathway has become a therapeutic target.
Several types of microRNAs (miRNAs) to suppress the production of inflammatory cytokines have been clarified; however, there were no methods for efficiently and stably delivering miRNAs to the affected area. miRNAs can be unstable in the blood, reducing their transfection efficiency to the target cells, so the use of miRNAs for treating IBD has rarely been attempted.
Osaka University researchers efficiently delivered miRNAs to immune response cells in inflamed intestinal tracts using a super carbonate apatite (sCA), which had been shown to be highly effective in the delivery of nucleic acids to solid tumors, demonstrating the efficacy of sCA in the prevention and treatment of colitis in mice. Their research results were published in Molecular Therapy-Nucleic Acids.
The researchers performed systemic administration of RNA (miR)-29a and miR-29b (both of which suppress inflammatory cytokines) loaded on sCA to IBD model mice. Although miRNAs didn’t accumulate much in the inflamed intestinal tracts, inflammatory cytokines were reduced, exhibiting the effects of prevention and treatment of colitis.
In addition, it was found that miRNAs loaded on sCA were efficiently delivered to the inflamed intestinal tracts’ dendritic cells (DCs), which play a central role in immune responses, suppressing the production of inflammatory cytokines.
This study clarified that the sCA functioned as a unique system for delivering nucleic acid-based medicines such as miRNAs to DCs in the affected area to suppress inflammatory reaction at the molecular level, exhibiting the effects of prevention and treatment of colitis.
Corresponding author Hirofumi Yamamoto says, “Our technique to deliver miRNAs to DCs, major players in immune responses, will shape the future of medical care. sCA can be used to treat a wide range of immunity and allergic disorders caused by immune responses. The results of our study will lead to the development of new drugs for treating these disorders.”
Citation for second study: Tadafumi Fukata et al. The Supercarbonate Apatite-MicroRNA Complex Inhibits Dextran Sodium Sulfate-Induced Colitis, Molecular Therapy – Nucleic Acids. DOI: 10.1016/j.omtn.2018.07.007