MRS7145: First photoactive drug to fight Parkinson’s

Institute of Neurosciences of the University of Barcelona
  • An international team of researchers designs a photoactive drug for the treatment of Parkinson’s disease
  • The developed photoactive drug, MRS7145, proves effective in animal models
  • The novel therapeutic development could be the foundation for new therapies against Parkinson’s disease

 

Parkinson’s disease and a few pharmacological considerations

Parkinson’s is the second most common neurodegenerative disease after Alzheimer’s, affecting more than 1 % of the population. In this disease, dopamine, the neurotransmitter that controls the motor activity, is reduced. The cause is the progressive death of dopaminergic neurons, responsible for the synthesis of dopamine. This condition of the nervous system currently affects over 6 million people worldwide, figures that according to estimates of the World Health Organization (WHO) could rise to 12 million by 2030.

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James Parkinson was the first person systematically describing Parkinson's, naming it "paralysis agitans" or "shaking palsy".

Not only in the context of Parkinson’s, the therapeutic efficacy of conventional drugs is sometimes diminished due to factors such as the lack of an adequate spatial specificity and speed in the drug distribution, or sufficiently well-localised place of action (in short, the arrival and action at the desired place). The efficacy in patients of the traditional treatment for Parkinson’s (levodopa or L-DOPA) diminishes over time. This forces to gradually increase the administered dose, or switch to alternative drugs. In addition to the previous, the adverse effects of new drugs as uncontrolled movements in the body, motor fluctuations, etc. are an undesired common denominator in numerous patients.

The reasons exposed highlight the value of the development of optopharmacology, an innovative discipline based on the use of light of specific wavelength to control precisely the place and time of action of photoactive drugs to treat diseases. Such light-sensitive drugs can act with a precise timing and a controlled location of their action. This entails, in practice, shielding parts of the body that do not need treatment against any undesired action of the medication. This has the clear potential to decrease dramatically the adverse effects experienced by patients.

 

MRS7145: A new photoactive drug?

An international team involving, among others, the Institute of Neurosciences of the UB (UB Neuro), has designed the drug MRS7145, the first potentially therapeutic photoactive drug to fight Parkinson’s disease. The research, published in the Journal of Controlled Release, had the participation of five other research institutions: locally, the Faculty of Medicine and Health Sciences of the University of Barcelona, the Bellvitge Biomedical Research Institute (IDIBELL), and the Chemistry Department of the Autonomous University of Barcelona, and internationally, the US National Institutes of Health and the Colgate University.

MRS7145 is the first potential therapeutic photoactive drug to fight Parkinson’s disease. It is a photosensitive derivate from SCH442416, a selective antagonist (essentially, an inactivator) of the adenosine receptor A2A. Some A2A antagonist receptors have been suggested as potential drugs to fight Parkinson’s, as they are involved in the mechanism controlling movement.

MRS7145 is an inactive chemical compound that, after delivery to the desired location, can be activated using non-harmful visible light radiation (at the 405 nm wavelength). In an experiment with laboratory animals, a series of optical fibers were planted into the striated body of the brain, responsible for motor activity. This provided a localised irradiation able to hit the inactive drug, transforming it into its active counterpart.

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Dr. Ciruela, leader of this research, with a few of his coworkers.

As describes the leader of this research, Lecturer Francisco Ciruela, “once the striated body is radiated with violet light, the active drug is released and blocks the adenosine A2A receptor. The blocking of adenosine receptors has an ‘administrating effect’ on the activity of dopamine”. This generates a pro-dopaminergic effect. That means that the dopamine-related activity in the brain, which is diminished in Parkinson’s patients, becomes effectively increased.

 

The impact on Parkinson’s treatment

Improving the precision of the space-time delivery of the actual drug to the desired site of action, and strengthening the adherence of the patient to the therapy are some of the benefits of optopharmacology in Parkinson’s. “A fine time-space precision will enable manipulating the neural circuits in close detail, enabling to direct their functioning for therapeutic and neuroprotective purposes”, said Dr. Ciruela.

“Nowadays, in addition, there are treatments that are based on the implementation of electrodes in the brain of patients with Parkinson’s to control the electric activity of neurons. In the same line, optical fibers could allow light to reach almost any part of the body (supplying spatial resolution). Organs could be radiated with light controlled by an electronic device regulating the intensity and time of radiation (providing time resolution).” Ciruela continues, “with a slow release system of the photoactive drug, such as a coupled patch with an irradiation device controlled remotely by a phone App, the doctor could control precisely the release of the most efficient dose of active drug in the place of action”.

Maintaining in the long run the commitment of patients to a set therapeutic regimen is a challenge in chronic diseases. Although the clinical application of this photoactive drug in patients is still far away, this pharmacological innovation could lead way to new therapeutical solutions for this chronic disease. It is therefore a step forward in the field of pharmacology to set innovative clinical protocols to improve patients’ quality of life.

 

 

Image credits:

Frontpage image Old Hands by Sharada Prasad CS downloaded and modified from Flickr and licensed with an Attribution 2.0 Generic (CC BY 2.0) license.

Image of James Parkinson, in the public domain, downloaded from Wikimedia Commons.

In-text image of researchers re-used with permission from the original article by the Institute of Neurosciences of the UB (UB Neuro).

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