First photopharmaceutical testing on mice against Parkinson’s

Photo: The MRS7145 photopharmaceutical is effective in animal models of the disease, according to research published in the Journal of Controlled Release./UB

A team led by the University of Barcelona has designed the first photopharmaceutical with therapeutic potential to fight against Parkinson’s. The compound, which is activated by light from the visible spectrum, has been tested in animal models. According to the authors, photosensitive drugs can act with greater spatial and temporal precision without generating harmful effects in the organism.

Francisco Ciruela, a researcher at the Faculty of Medicine and Health Sciences of the University of Barcelona, ​​has led the development of MRS7145, a photopharmaceutical to treat Parkinson’s. The results have been published in the Journal of Controlled Release.
Parkinson’s is the second most common neurodegenerative disorder after Alzheimer’s, and affects more than 1% of the population. The action of conventional drugs is often limited by several factors, such as the lack of spatial specificity, slow and imprecise distribution, which can reduce their therapeutic efficacy.

The optofarmacología, used in the new compound, is based on the use of light with a certain wavelength to control the activity of medicines. The photosensitive drugs can act with greater spatial and temporal precision, and without generating harmful effects in the organism.

According to the authors, MRS7145, the first photopharmaceutical with therapeutic potential against Parkinson’s, is a photosensitive derivative of SCH442416, a selective A2A adenosine receptor antagonist. In the scientific literature, some antagonists of A2A receptors have been revealed as potential drugs to combat Parkinson’s, since they participate in the mechanisms involved in the fine control of movement.
This photopharmaceutical is an inactive chemical compound until it is activated with light from the visible spectrum (with a wavelength of 405 nm) that is not harmful to the organism. A series of optical fibers implanted in the striatum of laboratory animals facilitate the irradiation of this region of the brain, responsible for the control of motor activity.
As Ciruela explains, “when the striatum is irradiated with violet light, the active drug is released and blocks the A2A adenosine receptor. Blockade of adenosine receptors has a facilitating effect on the activity of dopamine). “
Improving the spatial and temporal precision of the drug and reinforcing the patient’s commitment to therapy are some of the benefits of optopharmacology
Therapeutic and neuroprotective purposes

Improving the spatial and temporal accuracy of the drug and reinforcing the patient’s commitment to therapy are some of the benefits of the application of optofarmacology to Parkinson’s. “A finer spatio-temporal precision will allow us to manipulate neuronal circuits in more detail and establish their functioning for therapeutic and neuroprotective purposes,” emphasizes Ciruela.
Nowadays, in addition, there are treatments based on the implantation of electrodes in the brain of patients with Parkinson’s disease to control the electrical activity of neurons. With the same premise, optical fibers could also bring light to almost any part of the body (spatial resolution), and these organs would be irradiated with light controlled by an electronic device that would regulate the intensity and duration of radiation (temporal resolution) .

Maintaining the commitment of patients with the long-term fixed therapeutic regimen is a challenge in the case of chronic diseases. “With a slow-release system of the photopharmaceutical, for example, a patch coupled with an irradiation system and remotely controlled by an app in the mobile, the clinician could accurately control the release of the most effective dose of the active drug in the place of action “, emphasizes Ciruela.

Although the clinical application of this photopharmaceutical in patients is a distant milestone, this pharmacological innovation could open the way to the investigation of new therapeutic solutions against this chronic pathology, according to the authors.

Bibliographic reference:
J. Taura, E. G. Nolen, G. Cabré, J. Hernando, L. Squarcialupi, M. Lopez-Cano, K.A. Jacobson, V. Fernández-Dueñas, F. Plum. “Remote control of movement disorders using a photoactivable adenosine A2A receptor antagonist”. Journal of Controlled Release 283 (2018). May 2018. Doi: 10.1016 / j.jconrel.2018.05.033