Metabolic syndrome: New use for an old drug

November 18, 2019

New drugs can be developed from old ones. This revolutionary pharmacological approach that has been gaining ground recently was confirmed by a study conducted by two major research centres of the University of Trento that was published today in Nature Communications. The study, which investigated the relationship between diseases and pharmacological effects at molecular level, was jointly carried out by two research teams of the University: one at Cosbi (Fondazione The Microsoft Research - University of Trento Centre for Computational and Systems Biology), which is specialized in IT and big data, and one at Cibio Department, which is focused on biology and genomics.

First of all, the researchers examined the data: the existing drugs and, in particular, their molecular properties, were analyzed with a new algorithm designed by Cosbi, to see whether they could be used to treat other conditions, to bring benefits to patients with conditions that are difficult or impossible to treat. This technique, known as 'drug repositioning', has been already used in the past, but it has become even more effective today thanks to new technologies, which facilitate the quick and systematic analysis of a vast amount of data. We have achieved promising results, explained Enrico Domenici, president of Cosbi: "We have tested the new algorithm to search for new therapies to treat metabolic syndrome, a condition that increases the risk of heart disease and type 2 diabetes and which is characterized by obesity, elevated levels of cholesterol and/or triglycerides, high blood pressure and diabetes. We identified the mutated genes that are responsible for these alterations and then searched pharmaceutical databases for already approved molecules that could interact with the networks that these genes create in the adipose tissue, liver and muscles. To carry out such a complex study we adopted a new computational approach that measures the "distance" between the proteins targeted by the drug and those found in the networks affected by the disease. That is how we found a new purpose for an already existing drug: Ibrutinib, which was originally developed to treat completely different conditions, and specifically B-cell tumors like mantle cell lymphoma, chronic lymphocytic leukemia, and Waldenström macroglobulinemia. Other studies on this drug are under way to determine if it could be used to treat autoimmune diseases".

The results of the computational analysis were validated at Cibio on zebrafish larvae to confirm the response to the drug. The head of the research team at Cibio department, Maria Caterina Mione, explained how it worked: "When we tested this drug in the laboratory we saw that the devastating impact of obesity caused by a high-fat diet could be limited. The drug succeeded in limiting the inflammatory condition associated with lipid accumulation. Testing the effectiveness of a drug that is already on the market makes it possible to skip a number of long and complex stages of the approval process for new medical products, because their tolerance and safety have already been demonstrated. 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".

Finding out that a market approved drug can potentially be used to treat metabolic syndrome is great news. The incidence of the disease and seriousness of its consequences on health (cardiovascular diseases and diabetes complications), have made metabolic syndrome a social problem in recent decades, especially in wealthy societies, where many people have a diet high in sugars and fats and a sedentary lifestyle. In particular, the disease affects people over 50 years of age, about 30% of the male population and 35-40% of women. The metabolic syndrome becomes more common in women after menopause.

The study skipped a few phases of the drug development process and proved effective for repurposing a drug that was originally developed to treat other conditions. However, more needs to be done in the years to come as the research work will move to clinical trials.
-end-


Università di Trento

Related Diabetes Articles from Brightsurf:

New diabetes medication reduced heart event risk in those with diabetes and kidney disease
Sotagliflozin - a type of medication known as an SGLT2 inhibitor primarily prescribed for Type 2 diabetes - reduces the risk of adverse cardiovascular events for patients with diabetes and kidney disease.

Diabetes drug boosts survival in patients with type 2 diabetes and COVID-19 pneumonia
Sitagliptin, a drug to lower blood sugar in type 2 diabetes, also improves survival in diabetic patients hospitalized with COVID-19, suggests a multicenter observational study in Italy.

Making sense of diabetes
Throughout her 38-year nursing career, Laurel Despins has progressed from a bedside nurse to a clinical nurse specialist and has worked in medical, surgical and cardiac intensive care units.

Helping teens with type 1 diabetes improve diabetes control with MyDiaText
Adolescence is a difficult period of development, made more complex for those with Type 1 diabetes mellitus (T1DM).

Diabetes-in-a-dish model uncovers new insights into the cause of type 2 diabetes
Researchers have developed a novel 'disease-in-a-dish' model to study the basic molecular factors that lead to the development of type 2 diabetes, uncovering the potential existence of major signaling defects both inside and outside of the classical insulin signaling cascade, and providing new perspectives on the mechanisms behind insulin resistance in type 2 diabetes and possibly opportunities for the development of novel therapeutics for the disease.

Tele-diabetes to manage new-onset diabetes during COVID-19 pandemic
Two new case studies highlight the use of tele-diabetes to manage new-onset type 1 diabetes in an adult and an infant during the COVID-19 pandemic.

Genetic profile may predict type 2 diabetes risk among women with gestational diabetes
Women who go on to develop type 2 diabetes after having gestational, or pregnancy-related, diabetes are more likely to have particular genetic profiles, suggests an analysis by researchers at the National Institutes of Health and other institutions.

Maternal gestational diabetes linked to diabetes in children
Children and youth of mothers who had gestational diabetes during pregnancy are at increased risk of diabetes themselves, according to new research published in CMAJ (Canadian Medical Association Journal).

Two diabetes medications don't slow progression of type 2 diabetes in youth
In youth with impaired glucose tolerance or recent-onset type 2 diabetes, neither initial treatment with long-acting insulin followed by the drug metformin, nor metformin alone preserved the body's ability to make insulin, according to results published online June 25 in Diabetes Care.

People with diabetes visit the dentist less frequently despite link between diabetes, oral health
Adults with diabetes are less likely to visit the dentist than people with prediabetes or without diabetes, finds a new study led by researchers at NYU Rory Meyers College of Nursing and East Carolina University's Brody School of Medicine.

Read More: Diabetes News and Diabetes Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.