GENE therapy to treat neurological disorders such as Parkinson鈥檚 disease
or Alzheimer鈥檚 disease could damage the brain, warn researchers in Oxford. They
found that rats suffered severe brain damage after being given an experimental
form of gene therapy that relies on a common adenovirus to ferry in the
genes.
The researchers, from the department of human anatomy at the University of
Oxford, found that injections directly into the brain appeared to be harmless.
But when the same animals were injected with the adenovirus in the foot two
months later, they developed severe inflammation in the brain. At the moment,
the team has little idea why the rats鈥� immune systems reacted so violently to
the second injection, when the brain had already been exposed to the adenovirus
with no ill effects.
The experiments suggest that damage could be severe. As the rats鈥� immune
systems went to work on areas of the brain harbouring the virus, it led to the
type of inflammation found in people with multiple sclerosis. Brain and nerve
tissue became badly inflamed, and the myelin sheaths that protect brain cells
were stripped off.
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In healthy people, adenoviruses seldom cause much more than a mild cold or
diarrhoea. But attempts to use adenoviruses as gene shuttles to treat cystic
fibrosis have run into problems as patients suffered severe immune reactions.
One almost died.
The brain and the nervous system are relatively insulated from the body鈥檚
immune system by a membrane called the blood-brain barrier. This membrane gives
extra protection to the brain and nervous system, reducing their reliance on the
immune system for keeping infectious agents at bay. So attacks on the brain by
the body鈥檚 own immune system were unexpected. 鈥淚t鈥檚 bad news,鈥� says Matthew
Wood, a member of the team.
鈥淢ost people think that the immune system does not act very strongly in the
brain, but [our research] shows that it does,鈥� says Wood, who presented the
findings last week at a conference on gene therapy.
The experiments did yield some good news. The team, led by Harry Charlton,
found that the adenovirus delivered genes very efficiently when injected
directly into the brain. The inserted gene, which makes a 鈥渕arker鈥� protein
called b-galactosidase, carried on working for up to two months. And as long as
the adenoviruses were injected directly into the brain, there was no
inflammation.
But a second dose of the virus arriving in the animals鈥� bloodstream triggered
an unexpected backlash from the their immune system. The big worry for gene
therapists is that a patient鈥檚 immune system may already have been primed by a
natural infection to attack the adenovirus. Or patients might pick up an
infection after therapy, with equally devastating results.