June 16, 2017 University of Veterinary Medicine -- Vienna
Gene transfer as a treatment of
neurodegenerative diseases
Where viral vectors 'travel' and which types of neural cells they infect, can be visualized by fluorescent Proteins being transmitted.
Gene transfer is seen as
a hopeful therapy for Alzheimer's and Parkinson's patients. The approach
involves using harmless laboratory-produced viruses to introduce important
genes into the brain cells. In a study on mice, a team of researchers from
Vetmeduni Vienna for the first time investigated how far these viruses spread
in the brain and which cells they infect. Some of the artificial viruses
travelled from the injection site in the brain as far as the olfactory bulb or
the cerebellum and infected not only neurons but also other cells. The results,
which were published in the journal Histochemistry and Cell Biology,
could help to improve the selection of suitable viral "gene
transporters" for custom therapies using gene transfer. Purposefully
infecting brain cells with viruses may seem somewhat odd. But for patients
suffering from neurodegenerative diseases such as Alzheimer's or Parkinson's,
this type of therapy could be a glimmer of hope. The viruses used in this
approach do not trigger any disease themselves. They serve as harmless
transporters for genes specifically intended to treat these disorders. The
therapy, called gene transfer, uses the ability of viruses to insert their
genes into the genome of a host cell. This method could therefore be used to
purposefully introduce helpful genetic information into neurons.
Viral vectors don't stay
put
Viruses suitable for gene
transfer are injected into the brain. Previously, however, there had been no
studies of how far the viral transporters can spread from the injection site.
Earlier studies had usually only investigated the immediate area around the
injection canal. A new study with mice has now shown for the first time that
some of the tested viruses can travel long distances into different areas of
the brain. "In our study, we injected the viral vectors into key areas of
the cerebrum responsible, among other things, for the coordinationof body
movement ," explains Kirsti Witter from the Institute for Anatomy,
Histology and Embryology at Vetmeduni Vienna. From there, some of the viruses
spread into distant areas such as the cerebellum or the olfactory bulb.
"This information is important because, depending on the type of
neurodegenerative disease, it may be desirable to have as broad a distribution
of the virus as possible or to infect a specific, strictly delimited
area," says first author Juraj Hlavaty. "This study also shows that
all tested viruses can infect the neurons and the surrounding glial cells as
expected. Depending on the type of virus, however, there were differences in
the number and ratio of the infected cell types."
Inflammation could influence
which brain cells are infected
Depending on the virus
strain used, the injection triggered a mild or more pronounced reaction of the
nerve tissue in the treated mice. The stronger the immune response, the more
glial cells were infected. "The fact that individual viruses infected
these cells better than the neurons must, however, still be confirmed in future
experiments," says Hlavaty. The results of the work, achieved in
collaboration with the University of West Bohemia, Pilsen, Czech Republic, and
the Paul-Ehrlich-Institute, Langen, Germany, should contribute to improve the
selection of viral transporters. "The goal is to create a toolbox of
possible viruses in order to choose exactly the right transporter for the
custom treatment of a neurodegenerative disease," says Witter.
Artificial copies of
viruses as hopeful therapy
Copies of lentiviruses
are especially well-suited for gene transfer therapy. "The genome of
laboratory-produced lentiviruses consists only of areas that are necessary for
the infection and incorporation into the genome. This represents a fundamental
difference between these viruses and naturally occurring pathogenic
viruses," explains Hlavaty. Through the ability of the artificial viruses
to enter a host, the inserted human genes are introduced into the infected
cells to assume the tasks that the patients' cells no longer perform
themselves.
Story Source:
Materials provided
by University of Veterinary Medicine --
Vienna. Note: Content may be edited for style and
length.
Journal Reference:
1.
Juraj Hlavatý, Zbyněk Tonar, Matthias Renner, Sylvia Panitz,
Helga Petznek, Matthias Schweizer, Silke Schüle, Björn-Philipp Kloke, Rudolf
Moldzio, Kirsti Witter. Tropism, intracerebral distribution, and
transduction efficiency of HIV- and SIV-based lentiviral vectors after
injection into the mouse brain: a qualitative and quantitative in vivo study. Histochemistry
and Cell Biology, 2017; DOI: 10.1007/s00418-017-1569-1
http://www.sciencenewsline.com/news/2017061614340086.html
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