Anti-inflammatory therapy shows promise in slowing progression of
multiple sclerosis
Study shows using intranasal delivery method may reduce inflammation in
the brain

Date:
October 20, 2020
Source:
University of Alberta Faculty of Medicine & Dentistry
Summary:
Intranasal administration of an anti-inflammatory drug helped reduce
disease progression in a preclinical model of multiple sclerosis,
according to recent research.



FULL STORY ========================================================================== Intranasal administration of an anti-inflammatory drug helped reduce
disease progression in a preclinical model of multiple sclerosis,
according to recent research out of the University of Alberta.


========================================================================== Christopher Power, professor in the Faculty of Medicine & Dentistry,
and Leina Saito, a graduate student on his team, showed that delivering
an anti- inflammatory drug to mice helped prevent damage to brain cells, effectively slowing the progression of the disease.

MS is a devastating illness with no known cause and no cure. Power's lab
seeks to better understand the disease to develop effective treatments.

"Nerves in the brain are like insulated wires, but in MS there is
initially a loss of the insulation [called myelin], and then the eventual
loss of the wire.

Those losses are caused by inflammation. That inflammation, which we think
is the driving force for MS, is our main research interest," said Power,
a neurologist in the Northern Alberta MS Clinic, co-director of the U of
A's MS Centre and member of the Neuroscience and Mental Health Institute.

His research group is particularly interested in inflammasomes, molecules
that are responsible for the activation of an inflammatory response in
the body. For a disease such as MS, that response must be controlled to
halt the progression.

Power's lab identified a drug called VX-765 as a strong candidate therapy
for MS patients.

The drug works by inhibiting caspase-1, a component of inflammasomes
that promotes harmful inflammation in the body. In previous research,
Power's group saw beneficial results by delivering insulin intranasally
in other models of brain inflammation, and he decided to go with that
delivery route again. Using mouse models, Power dissolved VX-765 in a
fluid and then injected the mixture into the nose.

"It's a lot easier for patients because you need less of the drug. It's
a direct delivery into the brain, it doesn't go into the circulatory
system and it's not broken down as quickly," said Power of the intranasal delivery method.

To examine the impact of VX-765 on the nerves, Power collaborated
with researcher Frank Wuest, interim chair in the U of A's Department
of Oncology and member of the Cancer Research Institute of Northern
Alberta. Wuest is a world expert on positron emission tomography (PET) scanning, an imaging technique that uses radioactive substances to
visualize changes in the body.

Wuest used PET scans to look at brain metabolism and was able to document whether the insulation had been stripped or not after the therapeutic
was delivered.

"The study shows intranasal therapy is effective in preventing
demyelination and axon injury and loss, so that's a real tonic for
us to keep going," said Power. "The loss of myelin and loss of nerves
are irreversible processes, so any therapeutic that helps to slow or
prevent that from happening is an exciting advance for MS research. The particular delivery method also allows the therapy to be delivered in
a more precise and targeted way." The research was supported by an
Alberta Innovates-Health Solutions Collaborative Research and Innovation Opportunities Team grant, the University of Alberta Hospital Foundation
and the MS Society of Canada.


========================================================================== Story Source: Materials provided by University_of_Alberta_Faculty_of_Medicine_&_Dentistry.

Original written by Adrianna MacPherson. Note: Content may be edited
for style and length.


========================================================================== Journal Reference:
1. Leina B. Saito, Jason P. Fernandes, Mackenzie J. Smith, Matthew
A. L.

Doan, William G. Branton, Laura M. Schmitt, Melinda Wuest, Maria C.

Monaco, Eugene O. Major, Frank Wuest, Christopher Power. Intranasal
anti‐caspase‐1 therapy preserves myelin and glucose
metabolism in a model of progressive multiple sclerosis. Glia,
2020; DOI: 10.1002/glia.23896 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/10/201020131338.htm

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