Published Monday 11 June 2018
Fact checked by
Jasmin Collier
For
the very first time, scientists have developed a light-activated drug for
treating Parkinson's disease directly in a targeted part of the brain.
A new light-activated drug could help to treat
Parkinson's disease.
The drug — which is activated by shining light
down an optical fiber implanted in the brain — reduced Parkinson's symptoms and
improved motor function in mice.
In a paper about
the work now published in the Journal of Controlled Release, the
international team suggests that the "light-operated" drug could
potentially treat other movement disorders.
When activated by
light, the drug — called MRS7145 — blocks a protein called the "adenosine
A2A receptor."
Previous studies have already suggested that
the adenosine A2A receptor is a promising target for brain disorders such
as Parkinson's disease.
However, as the authors explain in their
paper, adenosine receptors are located throughout the brain, making it
difficult to use them for selecting and targeting only specific parts of the
brain.
By allowing "the spatiotemporal control
of receptor function," the new light-activated drug overcomes "some
of these limitations," note the authors.
Parkinson's and photopharmacology
In excess of 10 million of
the world's population has Parkinson's disease, including 1 million people in
the United States alone.
The disease is lifelong and gets worse with
time. It mainly affects movement, producing tremors, stiffness, slowness, and
problems with balance and coordination. Nonmovement symptoms can also arise,
such as constipation, disturbed
sleep, depression, anxiety,
and fatigue.
Parkinson's disease does not usually strike
before the age of 50; only around 10 percent of cases are diagnosed at an
earlier age.
It arises due to
death of nerve cells, or neurons, in a part of the brain called the substantia
nigra. These neurons make a chemical messenger called dopamine, which, among
other things, is important for controlling movement.
The goal of many drugs intended to treat
Parkinson's disease is to restore dopamine levels in the brain. The blocking of
adenosine receptors has been suggested as a target for such treatments, because
it can raise dopamine levels.
Photopharmacology is a relatively new medical
field that develops drugs whose power can only be switched on
and off using light.
The approach offers the possibility of
controlling the precise location of drug release in the body, thereby limiting
any off-target side effects. An example is the precise targeting of chemotherapydrugs to specific cancer cells.
It also allows precise timing of the release
of the drug. The release of type 2 diabetes drugs that
individuals can switch on and
off as and when required is an example of this.
Precisely timed dosing is a distinct advantage
in the use of drugs that gradually lose their efficacy and thus require bigger
doses to work. This is what happens with levodopa, the most common drug for
treating Parkinson's disease.
Light-activated drug tested in mice
MRS7145 is a light-sensitive derivate of
"SCH442416, [which is] a selective antagonist of adenosine A2A
receptor."
The compound is chemically inactive until it
is irradiated with light of wavelength 405 nanometers, which is in the violet,
visible part of the spectrum and not harmful to tissue.
For their study, the researchers ran a series
of tests. First, they showed that the drug responded to being triggered by
light in cells expressing the adenosine A2A receptor and blocked the receptor.
Then they tested the drug's effect on motor
function in live mice. They implanted an optical fiber into the appropriate
part of the mice's brains: the striatum.
When they shone
light of the correct wavelength down the fiber, the mice showed
"significant hyperlocomotion." This treatment also reduced the effect
of drug-induced rigidity and tremor.
Finally, they showed that the approach also
reversed "motor impairment" in a mouse model of Parkinson's disease.
Remote-controlled 'patch'
Co-corresponding author Dr. Francisco Ciruela,
of the Institute of Neurosciences at the University of Barcelona in Spain,
explains that there are already treatments for Parkinson's disease that use
wires implanted into the brain.
He and his colleagues caution that it is still
very early days yet, and that there is a lot of work to do before the
light-activated drug is ready for clinical use in a similar way.
Nevertheless, he envisages a future in which
the patient has a light-generating "patch" connected to the implanted
fiber.
Activation of the light, and thereby the
timing of drug release, could be controlled remotely by the doctor through a
smartphone app.
Such an approach may also help to minimize
dose-timing problems that typically occur in treating long-term illnesses, when
commitment to treatment schedules can begin to flag.
"A fine
time-space precision will enable manipulating the neural circuits in detail and
set the functioning of those with therapeutic and neuroprotective
purposes."
Dr. Francisco Ciruela
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