Cancer drug shows promise in treating metabolic syndrome

The research group at The Microsoft Research - University of Trento Centre for Computational and Systems Biology. Silvia Parolo, Pranami Bora, Lorena Leonardelli, Enrico Domenici. Image Credit: Alessio Coser.

A metabolic syndrome is a group of health problems characterized by the presence of elevated blood pressure, increased levels of triglycerides, high blood sugar, excess body fat around the waist, and obesity. If it’s left untreated, it can increase the risk of heart disease, stroke, and type 2 diabetes. Usually, treating metabolic syndrome involves targeting individual risk factors and modifying lifestyle practices.

Now, a team of researchers at the University of Trento found that the syndrome, which affects more than 35 percent of patients more than 50 years old in Western countries, could be treated with Ibrutinib, a drug used to treat some cancers.

Existing drugs to develop new ones

The study, published in the journal Nature Communications, emphasizes how science and medicine work to provide treatments for health problems that are considered difficult to manage. Metabolic syndrome, since it involves a cluster of various health conditions, can be a challenge to treat. New drugs can be developed from old ones, and these drugs can provide therapeutic effects for other diseases, too.

The researchers, who came from two teams, one from Cosbi, the Microsoft Research at the University of Trento Center for Computational and Systems Biology, focusing on big data and IT, and the other one from Cibio Department, which focuses on genomics and biology, wanted to investigate the connection between diseases and pharmacological effects at the molecular level.

They studied information from existing drugs and their molecular properties. From there, Cosbi designed an algorithm to determine if these drugs can be utilized for other health problems. They used this algorithm to see if some of these drugs designed for specific illnesses can be used for hard to treat conditions.

Using drug positioning

Drug positioning is a method that has been used in the past. Today, technology has evolved and became more effective. It can now aid in the fast and efficient analysis of large data to achieve results.

The algorithm has searched for new therapies to treat metabolic syndrome, a health condition that heightens the risk of cardiovascular disease, including heart disease, heart attack, and stroke, and type 2 diabetes.

With the use of the new algorithm, the team determined that mutated genes are responsible for alternations in the body of a person with metabolic syndrome. Then, they searched for already approved substances and ingredients that could interrelate with the networks the genes make in the liver, muscles, and adipose tissue.

Cancer drug shows promise

They found that a drug called Ibrutinib, which was originally developed to treat certain conditions, particularly B-cell tumors, including Waldenström macroglobulinemia, B-cell tumors, and chronic lymphocytic leukemia. The drug is used as an inhibitor of Bruton's tyrosine kinase (BTK).

To confirm the efficacy of the drug, the team validated the computational analysis of zebrash larvae. The researchers wanted to see the response to the drug. They found that the drug has limited the impact of obesity caused by consuming a high-diet. Further, the drug was successful in limiting the inflammatory condition tied to high lipid levels in the body.

The researchers reiterated that using previously approved drugs for other conditions makes it possible to find treatment while skipping the long and tedious stages of drug approval. The drug has already passed clinical trials and approval from regulatory agencies.

“Our data are just a start and more in-depth studies, and clinical tests are required, but they demonstrate that combining experience in big data analysis and the ability to develop models for biological validation can boost drug repurposing research,” Maria Caterina Mione, head of the research team at Cibio department, said.

What is metabolic syndrome?

Metabolic syndrome is a cluster of health problems that, when joined together, increase the risk of cardiovascular disease and type 2 diabetes. It has become a social problem over the past decades, mainly due to the consumption of a high-fat diet, foods high in added sugars, and having a sedentary lifestyle.

Usually, the disease affects people more than 50 years old, about 30 percent of the male population, and approximately 35 to 40 percent of women.

Metabolic syndrome becomes a diagnosis in people with a waist circumference of at least 37 inches among European men and at least 31.5 inches among European women. In Asians, the waist circumference in men is 35.5 inches and 31.5 inches in women.

Also, people have metabolic syndrome if they have an elevated blood pressure of more than 140/90 mmHg, increased triglyceride levels and low high-density protein (HDL) levels, poor blood glucose level control, and a higher risk of developing blood clots.

Journal reference:

Misselbeck, K., Parolo, S., Lorenzini, F. et al. A network-based approach to identify deregulated pathways and drug effects in metabolic syndrome. Nat Commun 10, 5215 (2019) doi:10.1038/s41467-019-13208-z, https://www.nature.com/articles/s41467-019-13208-z#citeas