Czech scientists develop peptide with potential to treat obesity

Illustrative photo: Tobyotter via / CC BY

Czech scientists have developed a synthetic peptide that could help treat obesity as well as several diseases. The patent for the substance has already been purchased by a major pharmaceutical company focused on diabetes. If further research goes well, the scientists hope it could be developed into a drug within six to eight years.

It all began 15 years ago, when biochemist Lenka Maletínská from the Institute of Organic Chemistry and Biochemistry at the Czech Academy of Sciences filed an application for a grant that would support her research into diabetes and obesity.

It was evaluated by Dr. Martin Haluzík, a diabetologist at the Institute of Clinical and Experimental Medicine (IKEM), who had just returned from the United States.

“I was on a scientific internship where I worked on research looking into experimental diabetes. I thought it would be useful to have someone in the Czech Republic who is focused on this issue.

“I was very interested and found out that Dr. Maletínská along with her fellow scientists at her institute are capable of developing several molecules with interesting properties. At the same time, I had just arrived with new experience of testing on mice. It was a lucky coincidence.”

Martin Haluzík,  photo: archive of IKEM

He would only tell Dr. Maletínská several years later that it was he who had to act as an opponent to her grant application. By then, the two had forged a successful partnership, working on a peptide that had been identified as a naturally produced hormone within the body during the late 1990s.

Peptides are aminoacids that can be used for treatment, ranging from skin care to weight-loss. However, as Dr. Maletínská explains, hormones externally ingested by themselves have little effect on the body, which is why they need to be modified scientifically.

“You can observe this substance naturally, for example in the brain of a mouse. But, if you wanted to use its natural form for treatment, it would basically be impossible. It would quickly dissolve and not pass through the blood-brain barrier. You would have to inject the hormone directly into an obese patient’s brain. Therefore, we had to think of a way to make the substance more stable.”

This can be done via a chemical process and the modification of the substance’s chemical effects. If a molecule with the desired effects is developed, it can then be tested on cells and thereafter on animals, such as mice.

Through a joint project between the chemistry institute and IKEM, a team of several dozen scientists would go on to develop such a substance. It showed promise of being able to tackle the body’s craving to eat, says Dr. Maletínská.

“We add a fat component. After that we get the peptide into the blood via injection under the skin and it gets through the blood-brain barrier.

“We are currently looking into how it affects the body, but it looks like one effect might be a change in the lipogenesis of fats. In simple terms that means that the fats get slimmer. So does the liver for example, which gets fatty among obese mice or human patients.”

The substance is currently being tested on mice. Results have shown that when injected with the modified peptide, these animals can lose 20 percent of their bodyweight within a space of two weeks. It is hoped that if it were made simple to use by human patients, it could help tackle obesity, because the peptide makes the brain think that it is already full.

Lenka Maletínská,  photo: archive of ÚOCHB

It is not the first peptide capable of fighting obesity. Indeed, some are already being used to treat patients. However, the one developed by the Czech team could significantly boost the effectiveness of weight loss drugs, says Dr. Haluzík.

“The success story of using peptides for treating obesity has already begun. A similar substance, called Glucagon-like peptide-1, was successfully clinically modified and is already used as a drug to help tackle obesity as well as diabetes. However, these hormones work through a different receptor.

“Where I believe that the peptide we are developing could make a huge difference is through combined use with drugs that are already implemented in treatment today. This could result in a major increase in the effectiveness of weight loss and therefore also help in the fight against associated complications. After all, it is not obesity itself that causes patients to die, but the resulting cardiovascular diseases, cirrhosis, and others.”

The potential of the Czech developed molecule has already been noted by Novo Nordisk, a major pharmaceutical company that specialises in obesity and diabetes. It has bought the patent for the peptide and is currently working on modifying it for use, says Dr. Haluzík.

“They have a wide portfolio ranging from insulins to peptides. If a company of this size, which can choose among several thousand if not tens of thousands of molecules, selects this one for research, it shows that it is an incredibly interesting substance.”

Novo Nordisk currently shares the grant provided for researching the uses of the molecule with the Institute of Organic Chemistry and Biochemistry. The latter is currently focusing on researching the potential of these substances on diabetes, obesity and Alzheimer's disease.

However, Dr. Maletínská says that it is still too early to be sure that the project will be successfully concluded.

“The likelihood that this will all end successfully is still at around one in a hundred. That said, when we started the research it was close to zero, so there certainly is hope. In any case, I believe that if anyone is capable of making it work, it is this company.”

If the project does indeed prove successful, the two scientists hope that the substance could be developed into a prescription drug within six to eight years. Dr. Haluzík says that if long-term weight loss is proven to alleviate diseases associated with obesity, the chance that the drug will be subsidised by health insurance companies will be much higher.

For now, he says it is important to highlight the dangers of obesity and start regarding it more as a disease, because it can lead to severe complications for the patient.