New Device For Administering Parkinson’s Treatment Shows Promise

There are two major stumbling blocks to developing effective drugs for Alzheimer's, Parkinson's,
and other diseases that destroy the brain. The first is overcoming the blood-brain barrier, and the
second is delivering the drug to a precise location and ensuring that it does not spread to the rest
of the brain.
Now, a new approach that uses ultrasound beams and microbubbles could be a noninvasive way
to deliver drugs safely to precise locations in the brain.
The technique is called focused ultrasound (FUS) and promises to open the door to thousands of
drugs that could treat a range of brain conditions if they could cross the blood-brain barrier.
The scientists at Columbia University in the city of New York who developed the FUS device
have now shown that it helped to curb early Parkinson's disease progression and improve brain
function in mice.
They describe the results in a recent Journal of Controlled Release study paper.
The FUS technique temporarily opens the blood-brain barrier in a specific part of the brain to
allow drugs to reach just that part.
The blood-brain barrier is a complex feature of the blood vessels that feed the brain and the rest
of the central nervous system.
The barrier prevents pathogens and potentially harmful substances crossing over from the
bloodstream into the parenchyma, or functional tissue, of the brain.
The FUS technique beams ultrasound pulses through the skull to a precise location in the brain.
When the pulses meet microbubbles that scientists have injected into the bloodstream, they cause
the microbubbles to oscillate between the walls of the tiny blood vessels.
The oscillating microbubbles cause a reversible increase in the permeability of the blood-brain
the barrier in that location.
When the FUS beams stop, the microbubbles stop oscillating, and the temporary access through
the blood-brain barrier closes.
For the recent study, the team focused on Parkinson's disease. They showed that they could use
FUS to deliver brain-altering genes and proteins across the blood-brain barrier.
Once across the barrier, the genes and proteins partly restored dopamine-releasing pathways in
the brain. Loss of ability to make dopamine — a chemical messenger that is important for
controlling movement — is an early feature of Parkinson's disease.
The researchers also saw reductions in some of the behavioral symptoms of Parkinson's disease
in the mice.

We found both behavioral and anatomical neuronal improvements in the brain,  says, Elisa
Konofagou, one of the senior study authors who is a professor of biomedical engineering and
also of radiology.
Prof. Konofagou says that she and her team are the first to use available drugs to restore a
dopamine-releasing pathway in early Parkinson's disease.
The Food and Drug Administration (FDA) in the United States has just granted the researchers
an Investigational Device Exemption so that they can safely test it as a way to deliver drugs in
people with Alzheimer's disease.
Prof. Konofagou' team is the only group in the U.S. that has gained approval from the FDA to
trial opening the blood-brain barrier using ultrasound. Others that are working in this field use
nanoparticles to open the blood-brain barrier or MRI for guiding the procedure.
The FUS device that Prof. Konofagou and her team have developed is smaller, faster, and
cheaper. It uses a single-element transducer instead of a helmet housing over 1,000 elements.
Also, its neuronavigation system" does not require MRI. The team likens it to the one that
neurosurgeons use except that it uses an ultrasound transducer instead of a surgical instrument.
The team envisages a portable FUS system that doctors can easily wheel in and out of patients'
rooms in a hospital, and one day, even in and out of their homes. In addition, treatment time lasts
only around half an hour instead of the 3 or 4 hours necessary for an MRI-guided procedure.
After the trial in people with Alzheimer's, Prof. Konofagou plans to test the device in people
with Parkinson's disease. We were able to curb the rapid progression of neurodegeneration
while improving the neuronal function. We expect our study will open new therapeutic avenues
for the early treatment of central nervous system diseases."


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