Researchers
have developed a gene therapy which successfully prevents Alzheimer’s disease
in mice. Clumping of beta amyloid proteins/monomers lead to the formation of
beta amyloid plaques. Scientist started by adding gene PGC-1? to a modified
virus and when it was delivered to the brains of mice suffering from early
stages of Alzheimer’s disease; it was able to target specific cells. It is said
that this gene prevents the formation of beta amyloid peptides and therefore prevents
the formation of beta amyloid plaques. From the results produced it was shown
that the mice which were injected with gene PGC-1?, developed very few amyloid plaques
and the mice which were not injected with this gene had several plaques.

The effect
of PGC-1? gene was tested on transgenic mice (these are mice which have
been genetically modified to produced increased levels of beta amyloid plaques).
The destroying nature of Alzheimer’s disease first appears in the hippocampus (part
of brain involved in memory) and the cortex (part of the brain which stimulates
cognitive thinking and reasoning skills).

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The way that
scientists delivered this gene into these mice was through a virus known as
lentivrius which can inject genetic material into other cells. The lentivirus
then delivered       PGC-1? gene into cells in the hippocampus and
the cortex where it interfered with the production if beta amyloid peptides and
beta amyloid plaques, therefore prevented the development of Alzheimer’s
disease.

Researchers
examined the brain of mice in the study. 
They found that there was a 19.1% reduction in beta amyloid peptides in
the cortex and a 30% reduction in the hippocampus of the PGC-1? mice
in comparison with the control mice (mice not injected with gene). Beta
amyloid plaque buildup reduced by 43% in the cortex and 51% in the hippocampus
of the PGC-1? mice in comparison with the controls. 

There was
inflammation surrounding the beta amyloid plaques which contributed to the
destruction of neurons was reduced significantly in the mice where the gene had
been introduced compared to the mice which acted as controls. There was no
significant loss of neurons in mice treated with gene however control mice had
30% fewer neurons in hippocampus region of their brain. Therefore the results provide
strong evidence that PGC-1? could potentially to prevent the development
of Alzheimer’s disease in the future.

Reduction in
beta amyloid was achieved in mice injected with PGC-1? , through reducing the
expression of enzymes involved in beta amyloid production by preserving neurons
in the brain which resulted in mice performing as well as wild-type mice in
cognitive tests. We can therefore conclude that the PGC-1? selective delivery
shows promising results for decline Alzheimer’s disease through the use of gene
therapy. There are several Transcription factors which play a significant role
in regulating BACE1 gene expression and such regulation affects beta secretase
processing of APP and beta amyloid production.PGC-1?  regulates the transcription of beta amyloid
cleaving enzyme beta secretase (BACE1), which is the main enzyme involved in
beta amyloid production. Also its expression is decreased in patients suffering
from this disease.

Since it is
the mutation in the APP gene that produces beta amyloid plaques through beta
and gamma secretase enzyme activities. We can conclude that this form of
gene therapy plays a crucial role in possibly finding a cure for Alzheimer’s disease
in the future because it involves the implementation of the PGC-1? which
targets the processing of the APP gene through transcriptional factors which
therefore reduces the formation of  beta
amyloid through regulation of the enzyme. In this case I have learnt how the
gene therapy had a huge impact on the APP gene and regulated the production of
plaques which suggests that to possible treat/cure the disease.

It was shown
that mice which were injected with this form of gene therapy during the early
stages of Alzheimer’s disease did not develop any plaques. After four months
they performance in  memory tasks was
equivalent to the performance healthy mice. The senior author of research at
the department of medicine at imperial college stated that one day these
finding may contribute towards finding a cure for disease by halting it during
the early stages. She said, “Although these findings are very early they
suggest this gene therapy may have potential therapeutic use for patients” However
we have to consider the fact that further investigations need to take place as
there are many hurdles to overcome as the only way to directly deliver the gene
via injection into the brain. Clinical trials had been carried out on patients
suffering with Parkinson’s disease and it had proven to be successful however
the medcial team from imperial college believe that injections of the gene
would be most be most beneficial only in the early stages of the disease when
the symptoms first appear and although there is new research that explores gene
therapy as a possible treatment strategy for the disease, further studies are
required to establish whether gene therapy would be safe , effective and practical
to use in people with the disease. Before the effectiveness of this technology can
be conducted in Alzheimer’s patients several years of clinical trials and
safety studies need to be conducted. Beta amyloid plaques in transgenic mice
have a similar structure to those found in the human brain. They consist mainly
of mainly of A?42 and therefore develop a dense A?42 core, however also
have A?40 incorporated, as well as numerous other non beta amyloid components.
Many transgenic mouse models exhibit memory problems and usually cognitive deficits
appear occur earlier than the appearance of plaques. These observations led to
a search for earlier pathological species of beta amyloid that could be
mediating cognitive decline. However, in humans, unlike AD transgenic mice,
cognitive decline does not begin until there is a large quantity of beta
amyloid plaques accumulated in the brain. From this evidence I can conclude
that even though this technique has been proven to be successful in mice, we do
not know as of yet how this is going to work in humans so therefore further
investigations are required.