Researchers study new drug for the treatment of Parkinson’s

A team of researchers from Department of Chemistry and Biochemistry from the Faculty of Sciences of the University of Porto (FCUP) is working on a new drug for the treatment of Parkinson’s diseasemore efficient and with fewer side effects than those currently used.

Parkinson’s disease is a neurodegenerative disorder that results from the loss of neurons that produce an important neurotransmitter, dopamine, responsible for physiological processes such as cognition, memory, emotions and movement control.

The drugs on the market aim to increase the production of dopamine in the central nervous system. However, over the years, these medications lose their effectiveness, making it necessary to administer higher doses, which results in side effects that, in many cases, can even exacerbate the symptoms of the disease.

“Our target is different: we focus on modulating dopamine receptors”, he begins by explaining Ivo Dias, researcher at the Associated Laboratory for Green Chemistry (LAQV-REQUIMTE) at FCUP who leads the research team. “What happens in Parkinson’s disease is that low levels of dopamine are not sufficient to activate the receptors appropriately and, therefore, compromise the activation of dopaminergic circuits. What we want is to increase the affinity of these receptors for dopamine and, thus, ensure that motor symptoms are attenuated even at low concentrations of this neurotransmitter”, he highlights.

Improve in the laboratory a potential drug that exists naturally in our body

To this end, FCUP researchers are developing, in the laboratory, within the scope of the DynaPro project, funded by the Foundation for Science and Technology, analogues of a neuropeptide, melanostatin. Melanostatin, discovered in the 70s, exists naturally in our body, and is known for its anti-Parkinson’s activity, already proven in clinical trials. The aim is to improve its therapeutic potential, making it a drug candidate: with greater biological stability and improved gastrointestinal absorption.

“We discovered that one of the three amino acids that make up this substance can be modified at a structural level without harming the modulating activity of dopamine receptors: proline”, describes the researcher.

And it is based on this modification that the FCUP team, within the scope of the DynaPro project, has already achieved promising results. Together with partners from the University of Santiago de Compostela, they verified that the compounds developed in the laboratory are not only more efficient, but also do not present toxicity in neuronal cells. “We found that some of our analogues are even more potent than melanostatin, managing to activate receptors at an even lower concentration of dopamine”, he says.

A pioneering therapeutic approach with promising results

With this new pharmacological approach, there is also an advantage in terms of side effects: “they are very reduced because melanostatin has no activity in the absence of dopamine”.

The FCUP team is one of the few in the world working on this therapeutic approach and is the only one in Portugal to focus on dopamine receptor modulators, which include melanostatin.

The DynaPro project ends later this year and the researchers are preparing, given the promising results, to submit a patent application.

As next steps, they intend to carry out tests with models in vivo to test the therapeutic potential of these compounds in different animal species.

This project is led by LAQV-REQUIMTE at FCUP and also includes researchers from the Faculty of Science and Technology of the University of the Basque Country and the Faculty of Pharmacy of the University of Porto and the University of Santiago de Compostela.

The FCUP team is part of Ivo Dias It is José Enrique Borgesprofessors at FCUP and integrated researchers at LAQV-REQUIMTE, and researchers at LAQV-REQUIMTE Sara Reis, Hugo Almeida It is Beatriz Lima, PhD students in Sustainable Chemistry at FCUP It is Xavier Correia, alumnifrom FCUP and also a researcher at this research center.

It also includes the participation of researcher Vera Costa, from the Faculty of Pharmacy of the University of Porto and professors Xerardo Mera from the University of Santiago de Compostela and Humberto Díaz, from the University of the Basque Country.

Faculty of Sciences of the University of Porto