January 26, 2018 - Dr Zara Kassam (European Pharmaceutical Review)
Miniaturised system could be used to treat neurological disorders that affect specific brain regions…
Researchers have devised a miniaturised system
that can deliver tiny
quantities of medicine to brain regions as small as 1 cubic millimetre. This
type of targeted dosing could make it possible to treat diseases that affect
very specific brain circuits, without interfering with the normal function of
the rest of the brain, the researchers say.
The MIT team set out to
develop a miniaturised cannula that could target very small areas. Using
microfabrication techniques, the researchers constructed tubes with diameters
of about 30 micrometres and lengths up to 10 centimetres. These tubes are contained
within a stainless steel needle with a diameter of about 150 microns. “The
device is very stable and robust, and you can place it anywhere that you are
interested,” says Canan Dagdeviren, the LG Electronics Career Development
Assistant Professor of Media Arts and Sciences.
The researchers
connected the cannulas to small pumps that can be implanted under the skin.
Using these pumps, the researchers showed that they could deliver tiny doses
(hundreds of nanoliters) into the brains of rats. In one experiment, they
delivered a drug called muscimol to a brain region called the substantia nigra,
which is located deep within the brain and helps to control movement.
Even if scientists and clinicians can identify a therapeutic
molecule to treat neural disorders, there remains the formidable problem of how
to deliver the therapy to the right cells
Previous studies
have shown that muscimol induces symptoms similar to those seen in Parkinson’s
disease. The researchers were able to generate those effects, which include
stimulating the rats to continually turn in a clockwise direction, using their
miniaturised delivery needle. They also showed that they could halt the
Parkinsonian behaviour by delivering a dose of saline through a different
channel, to wash the drug away.
“Since the device
can be customisable, in the future we can have different channels for different
chemicals, or for light, to target tumours or neurological disorders such as
Parkinson’s disease or Alzheimer’s,” Prof Dagdeviren says.
This device could
also make it easier to deliver potential new treatments for behavioural
neurological disorders such as addiction or obsessive-compulsive disorder,
which may be caused by specific disruptions in how different parts of the brain
communicate with each other.
“Even if scientists and clinicians can identify a
therapeutic molecule to treat neural disorders, there remains the formidable
problem of how to deliver the therapy to the right cells — those most affected
in the disorder. Because the brain is so structurally complex, new accurate
ways to deliver drugs or related therapeutic agents locally are urgently
needed,” says Ann Graybiel, an MIT
Institute Professorand a member of MIT’s McGovern Institute for
Brain Research, who is also an author of the paper.
The researchers
also showed that they could incorporate an electrode into the tip of the
cannula, which can be used to monitor how neurons’ electrical activity changes
after drug treatment. They are now working on adapting the device so it can
also be used to measure chemical or mechanical changes that occur in the brain
following drug treatment.
The cannulas can
be fabricated in nearly any length or thickness, making it possible to adapt
them for use in brains of different sizes, including the human brain, the
researchers say.
Using this
device, which consists of several tubes contained within a needle about as thin
as a human hair, the researchers can deliver one or more drugs deep within the
brain, with very precise control over how much drug is given and where it goes.
In a study of rats, they found that they could deliver targeted doses of a drug
that affects the animals’ motor function.
“We can infuse
very small amounts of multiple drugs compared to what we can do intravenously
or orally, and also manipulate behavioural changes through drug infusion,” says
Prof Dagdeviren.
“We believe this tiny microfabricated device could have a
tremendous impact in understanding brain diseases, as well as providing new
ways of delivering biopharmaceuticals and performing biosensing in the brain,”
says Robert Langer, the
David H. Koch Institute Professor at MIT and one of the paper’s senior authors.
The research has been published in Science Translational
Medicine.
https://www.europeanpharmaceuticalreview.com/news/72127/miniaturised-neural-system/
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