Three potential new targets for treating epilepsy

Date:
June 25, 2020
Source:
RCSI
Summary:
A major international study has uncovered three molecules that have
the potential to be developed into new drugs to treat epilepsy. The
findings are an important step towards discovering new drugs for
people with epilepsy whose seizures cannot be controlled with
current treatments.



FULL STORY ==========================================================================
A major international study has uncovered three molecules that have
the potential to be developed into new drugs to treat epilepsy. The
findings are an important step towards discovering new drugs for people
with epilepsy whose seizures cannot be controlled with current treatments.


==========================================================================
The study was led by researchers at FutureNeuro, the SFI Research
Centre for Chronic and Rare Neurological Diseases and RCSI University
of Medicine and Health Sciences. It is the result of seven years of
research, involving contributions from 35 scientists, based in eight
different European countries, across the fields of neuroscience, genetics, computer science and synthetic chemistry. The research is published in
the Proceedings of the National Academy of Sciences (PNAS) USA.

In one of the largest sequencing projects of its kind, researchers
identified and measured levels of over a billion strands of microRNAs,
small molecules that control gene activity in the brain, to investigate if
they were changed in epilepsy. They discovered a small set of microRNAs
which were always elevated in epilepsy and designed drug-like molecules, synthesized by chemists from the group, to target these. Three of the
synthetic molecules were found to stop seizures in preclinical tests.

Computer simulations demonstrated how the potential treatments influenced molecule networks inside brain cells by changing the inflammatory
response, part of the brain's immune system which is thought to contribute
to seizures.

"Our approach to drug discovery has led us to new types of molecules
that can be targeted to prevent seizures with hopefully fewer side
effects." said Dr Cristina Reschke, FutureNeuro Research Fellow and
Honorary Lecturer at RCSI, and Co-Lead Author. "Currently, most drugs
used to treat epilepsy work by blocking the signals brain cells use
to communicate. This results in many of the side effects experienced
by people with epilepsy." Epilepsy is one of the most common chronic
brain diseases, affecting over 40,000 people in Ireland and 65 million
people worldwide. People with epilepsy are prone to repeated seizures,
but for the majority of people, these can be well controlled. There are
more than 20 medicines available to prevent seizures in people with
epilepsy, but progress has slowed in recent years and new treatments
offer little benefit over those that have been around for decades.

"By characterising and targeting an entire new class of molecules
in epilepsy, we hope to develop novel and innovative treatment
strategies for temporal lobe epilepsy." said Dr Gareth Morris, Marie Sklodowska-Curie Actions Fellow at FutureNeuro and Co-Lead Author of
the paper. "This is an important step closer to fulfilling the urgent
and unmet clinical needs for the one third of people whose seizures are resistant to currently available drugs." Senior author on the study,
Professor David Henshall, Director of FutureNeuro and Professor of
Molecular Physiology and Neuroscience at RCSI said: "The project is
a great example of team science, where groups with different areas of
expertise combine to create innovative solutions that keep people with
epilepsy as the central focus. The discoveries here may be just the
tip of the iceberg for new strategies in the treatment of epilepsy. I'm optimistic this can be translated to the clinic."

========================================================================== Story Source: Materials provided by RCSI. Note: Content may be edited
for style and length.


========================================================================== Journal Reference:
1. Morten T. Veno/, Cristina R. Reschke, Gareth Morris, Niamh M. C.

Connolly, Junyi Su, Yan Yan, Tobias Engel, Eva M. Jimenez-Mateos,
Lea M.

Harder, Dennis Pultz, Stefan J. Haunsberger, Ajay Pal, Janosch
P. Heller, Aoife Campbell, Elena Langa, Gary P. Brennan, Karen
Conboy, Amy Richardson, Braxton A. Norwood, Lara S. Costard,
Valentin Neubert, Federico Del Gallo, Beatrice Salvetti, Vamshidhar
R. Vangoor, Amaya Sanz- Rodriguez, Juha Muilu, Paolo F. Fabene,
R. Jeroen Pasterkamp, Jochen H.

M. Prehn, Stephanie Schorge, Jens S. Andersen, Felix Rosenow,
Sebastian Bauer, Jo/rgen Kjems, David C. Henshall. A systems
approach delivers a functional microRNA catalog and expanded targets
for seizure suppression in temporal lobe epilepsy. Proceedings
of the National Academy of Sciences, 2020; 201919313 DOI:
10.1073/pnas.1919313117 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/06/200625115917.htm

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