Can an experimental diabetes drug change how we treat heart disease?
In a new study, researchers tout the drug trodusquemine’s ability to “melt away” arterial fat in preclinical trials involving mice.
“We could show that using the drug chronically, once a week for five weeks or just once toward the end of the study, both resulted in significantly lower atherosclerotic plaque area. It also lowered serum lipids (triglycerides and cholesterol),” Mirela Delibegovic, a study author and a professor in diabetic medicine at the University of Aberdeen, told Healthline.
Mice in the study were treated with either saline (for the control group), a single trodusquemine dose, or multiple doses.
For mice receiving single or multiple doses, there was a decrease in the measured plaque formation while the control group remained unchanged.
The study at Aberdeen is exciting because, in Delibegovic's words, “[The drug] seemed to completely reverse the effects of” atherosclerosis.
Tackling a major killer
Heart disease is the leading cause of death for both men and women in the United States, according to the Centers for Disease Control and Prevention (CDC).
An estimated 610,000 people die per year from heart disease in the United States, accounting for roughly 25 percent of all deaths annually.
Additionally, more than 700,000 Americans will have a heart attack each year.
Atherosclerosis, the narrowing of arteries caused by a buildup of fatty plaque, is a leading cause of heart attack and stroke.
While the condition is present in all people to some degree, it gets worse as you get older.
It can be affected by many lifestyle factors, including diet, activity level, and smoking.
Atherosclerosis slows blood flow to and from the heart, leading to coronary heart disease, angina, and other, more severe, health complications.
Occlusion, the blocking of a blood vessel, can result in serious, sometimes fatal cardiac incidents. Plaque can also dislodge from the blood vessel resulting in a blood clot (thrombosis).
How the drug works
Trodusquemine works by inhibiting PTP1B, an enzyme in the body that has a role in insulin regulation.
It may also help in treating diabetes — which makes the drug’s potential even more intriguing.
“Cardiovascular disease is the most prevalent cause of mortality in diabetic patients, due to accelerated atherosclerosis. Thus drugs that could improve both the diabetic status and decrease atherosclerotic progression may hold promise for future therapies,” said Delibegovic.
There is also a strong connection between diabetes, heart disease, and atherosclerosis.
Being able to treat obesity, diabetes, and atherosclerosis with one drug would be groundbreaking.
Atherosclerosis is considered a chronic, low-level inflammatory disease, which is accelerated by diabetes.
Prior studies showed that diabetes worsened atherosclerosis. In 2008, a study from the University of Rochester identified the biological mechanisms for why this occurred.
“We have known for a number of years that inhibition of the protein PTP1B should result in positive outcomes on whole-body insulin sensitivity. We have now added to the evidence that it is also positive in regards to atherosclerosis development,” said Delibegovic.
At this point, trodusquemine is in early clinical trials for the treatment of diabetes and breast cancer.
Further studies will be required to test whether or not the drug’s ability to reverse atherosclerosis is possible in humans.
Delibegovic and her colleagues are looking forward to continuing their research on the drug.
She says they are currently applying for funding to conduct human trials.
“We plan to continue our research moving onto the human setting now that we have the positive preclinical data,” Delibegovic said.