A new compound that becomes therapeutically active when stimulated by light was able to reverse motor symptoms in a mouse model of Parkinson’s disease.
The distinctive features of this investigational compound, called MRS7145, include more control when delivering the therapy and fewer side effects.
The study about MRS7145, “Remote control of movement disorders using a photoactive adenosine A2A receptor antagonist,” was published in the Journal of Controlled Release.
Levopoda is considered the gold standard to treat Parkinson’s disease, as it counteracts the reduced levels of dopamine caused by the death of brain cells that characterize this disease. However, the inability to specifically deliver the drug to targeted sites, as well as its generalized negative effect on the body, can limit levopoda’s therapeutic activity and effectiveness.
So, for the past two decades, alternative non-dopaminergic drugs, such as adenosine A2A receptor (A2AR) antagonists, have emerged as promising anti-Parkinsonian therapies.
A2AR antagonists can modulate the release of key neurotransmitters in the brain, which modulates motor activity. Unfortunately, A2ARs are expressed throughout the body, which can cause A2AR-based drugs to have off-target effects, and limiting the use of A2AR antagonists therapeutically.
To overcome some of these limitations, a new class of compounds that can be activated — or inactivated — using light have emerged. These compounds allow physicians to control the specific location of drug release, leading to targeted administration and, consequently, limiting side effects.
MRS7145 is the first photoactive selective antagonist of adenosine A2A receptor designed for the treatment of Parkinson’s and other disorders characterized by uncontrolled movement (dyskinesia).
MRS7145 is generally chemically inactive. However, when exposed to non-harmful violet light MRS7145 turns “on” and is able to carry out its function.
Using cells in the laboratory, researchers showed that MRS7145 could effectively bind and block the activity of A2A receptors upon light activation.
Next, MRS7145 was put into a mouse model of Parkinson’s disease. By applying the violet light directly to the striatum area of the mice’s brains — the region most affected by Parkinson’s disease — the compound was activated in that location only.
Treatment led to significant improvements in mice’s ability to walk, while also reducing tremor and seizures. Importantly, it enhanced the effects of levodopa treatment in these animals.
“A fine time-space precision will enable manipulating the neural circuits in detail and set the functioning of those with therapeutic and neuroprotective purposes,” Francisco Ciruela, PhD, said in a press release. Ciruela is a researcher at the Faculty of Medicine and Health Sciences of the University of Barcelona, and senior author of the study.
“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 lines, optical fibers could make light getting to almost any part of the body (spatial resolution), and these organs would be radiated with light controlled by an electronic device that would regulate the intensity and length of radiation (time resolution),” Ciruela said.
“With a slow release system from the photoactive drug, such as a coupled patch with a radiation system remotely controlled by a phone app, the doctor could control in a precise manner the release of the most efficient dose of the active drug in the place of action,” he said.