Researchers have prevented the development of
Alzheimer's disease in mice by using a virus to deliver a specific gene into
the brain
Newswise, October 17, 2016— Researchers have prevented the
development of Alzheimer's disease in mice by using a virus to deliver a
specific gene into the brain.
The early-stage findings, by scientists from Imperial College
London, open avenues for potential new treatments for the disease.
In the study, published in the journal Proceedings of
the National Academy of Sciences, the team used a type of modified virus to
deliver a gene to brain cells.
The research was funded by Alzheimer's Research UK and the
European Research Council.
Previous studies by the same team suggest this gene, called
PGC1 - alpha, may prevent the formation of a protein called amyloid-beta
peptide in cells in the lab.
Amyloid-beta peptide is the main component of amyloid plaques,
the sticky clumps of protein found in the brains of people with Alzheimer's
disease. These plaques are thought to trigger the death of brain cells.
Alzheimer's disease affects around 520,000 people in the UK.
Symptoms include memory loss, confusion, and change in mood or personality. Worldwide
47.5 million people are affected by dementia - of which Alzheimer's is the most
common form.
There is no cure, although current drugs can help treat the
symptoms of the disease.
Dr Magdalena Sastre, senior author of the research from the
Department of Medicine at Imperial, hopes the new findings may one day provide
a method of preventing the disease, or halting it in the early stages.
She explained: "Although these findings are very early
they suggest this gene therapy may have potential therapeutic use for patients.
There are many hurdles to overcome, and at the moment the only way to deliver
the gene is via an injection directly into the brain. However this proof of
concept study shows this approach warrants further investigation."
The modified virus used in the experiments was called a
lentivirus vector, and is commonly used in gene therapy explained Professor
Nicholas Mazarakis, co-author of the study from the Department of Medicine:
"Scientists harness the way lentivirus infects cells to produce a modified
version of the virus, that delivers genes into specific cells. It is being used
in experiments to treat a range of conditions from arthritis to cancer. We have
previously successfully used the lentivirus vector in clinical trials to
deliver genes into the brains of Parkinson's disease patients."
In the new study, the team injected the virus, containing the
gene PGC-1 - alpha, into two areas of the brain in mice susceptible to
Alzheimer's disease.
The areas targeted were the hippocampus and the cortex, as
these are the first regions to develop amyloid plaques in Alzheimer's disease.
Damage to the hippocampus affects short-term memory, and leads
to a person forgetting recent events, such as a conversation or what they ate
for breakfast. The hippocampus is also responsible for orientation, and damage
results in a person becoming lost on familiar journeys, such as driving home
from the shops.
The cortex, meanwhile, is responsible for long-term memory,
reasoning, thinking and mood. Damage can trigger symptoms such as depression,
struggling to work out how much money to give at a checkout, how to get dressed
or how to cook a familiar recipe.
The animals were treated at the early stages of Alzheimer's
disease, when they still had not developed amyloid plaques. After four months,
the team found that mice who received the gene had very few amyloid plaques,
compared with the untreated mice, who had multiple plaques in their brain.
Furthermore, the treated mice performed as well in memory
tasks as healthy mice. The tasks included challenges such as replacing a
familiar object in the mouse's cage with a new one. If the mice had a healthy
memory, they would explore the new object for longer.
The team also discovered there was no loss of brain cells in
the hippocampus of the mice who received the gene treatment. In addition to
this, the treated mice had a reduction in the number of glial cells, which in
Alzheimer's disease can release toxic inflammatory substances that cause
further cell damage.
The protein PGC-1 - alpha, which is coded by the gene, is
involved in metabolic processes in the body, including regulation of sugar and
fat metabolism.
Dr Sastre added that other studies from different institutions
suggest physical exercise and the compound resveratrol, found in red wine, may
increase levels of PGC-1 - alpha protein. However, resveratrol has only been
found to have benefits as a pill, rather than in wine, as the alcohol
counteracts any benefit.
The team suggest injections of the gene would be most
beneficial in the early stages of the disease, when the first symptoms appear.
They now hope to explore translating their findings into human
treatments, said Dr Sastre.
"We are still years from using this in the clinic.
However, in a disease that urgently needs new options for patients, this work
provides hope for future therapies."
Dr David Reynolds, Chief Scientific Officer at Alzheimer's
Research UK, said: "There are currently no treatments able to halt the
progression of damage in Alzheimer's, so studies like this are important for
highlighting new and innovative approaches to take us towards that goal.
“This research sets a foundation for exploring gene therapy as
a treatment strategy for Alzheimer's disease, but further studies are needed to
establish whether gene therapy would be safe, effective and practical to use in
people with the disease.
“The findings support PGC-1-alpha as a potential target for
the development of new medicines, which is a promising step on the road towards
developing treatments for this devastating condition."
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