Athens Macedonian News Agency: News in English, 17-03-28

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From: The Athens News Agency at <http://www.ana.gr/>

CONTENTS

[01] Greek research team's findings spark new hope for Parkinson's cure

[01] Greek research team's findings spark new hope for Parkinson's cure

In an interview with the Athens-Macedonian News Agency (ANA) on Tuesday, the head of the team of researchers Demetrios Vassilatis, of the Biomedical Research Foundation of the Academy of Athens (BRFAA), noted that the discovery was still at a preclinical stage but might lead to a new treatment route in the future for the specific neurodegenerative disease, which affects millions of people worldwide.

ANA: What is it that your research team has succeeded in doing, exactly?

Vassilatos: My research team in the United States, in collaboration with the neurology team at Baylor College of Medicine, was the first to discover the mutations that supress the Nuclear receptor-related 1 (Nurr1) gene in patients with Parkinson's Disease. The research in my laboratory in Athens in recent years has focused on answering the question whether the activation of the Nurr1 can be therapeutic in animal models of Parkinson's Disease. Because in the dopaminergic neurons, Nurr1 creates a heterodimer (a molecule composed of paired proteins with some amino-acid sequence variations) with Retinoid X receptor A (RXRa), we decided to target Nurr1:RXR� chemically.

In collaboration with Dr. Demosthenes Fokas of Ioannina University, we discovered various chemical compounds, among them BRF110, that selectively activate Nurr1:RXR�. In my laboratory at the BRFAA with my colleague Dr. Athanasios Spathis, we showed that BRF110 not only has the capacity to protect dopaminergic neurons from degeneration but also to improve the symptoms in animal models of Parkinson's Disease.

ANA: What is the significance of your discovery compared to other research taking place worldwide related to Parkinson's Disease?

Vassilatos: The gradual degeneration of dopaminergic neurons typical of Parkinson's Disease leads to a loss of dopamine that is responsible for the disease's motor symptoms. The existing treatments replenish dopamine and improve the motor symptoms of patients.

They do not, however, stop the degeneration of the neurons and their long-term use induces dyskinesias (stiffness) that negate their beneficial action. Efforts to find neuroprotective factors stumble on their reliable assessment in clinical trials, partly due to their inability to offer improvement to patients' symptoms.

Our experiments show that activation of Nurr1 through BRF110 in pre-clinical animal models is simultaneously neuroprotective but also replenishes the lack of dopamine, with immediate improvement of symptoms. Furthermore, long-term use of BRF110 does not induce dyskinesias.

ANA: What will your next research steps be? Are clininal trials on people likely and, if so, in roughly how many years?

Vassilatos: The questions arising from our experiments are many and the research required has many levels, including the basic and translational research. The discovery of pharmaceuticals is a lengthy and multi-stage process and we are in a pre-clinical stage.

We would like to be the first to assess Nurr1 activators/antagonists in clinical trials. In this direction, we worked with Dr. Jens Schwamborn from the Luxembourg Centre for Systems Biomedicine (LCSB) and assessed BRF110 on dopaminergic neurons derived from the stem cells of a Parkinson's Disease patient with very positive results.

The next stages include improving the existing chemical compounds in potential clinical molecules, which could be developed in the next two to three years.

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