A LINK between Alzheimer鈥檚 disease and herpes simplex virus 1, which
causes cold sores, has raised fears about the safety of proposed gene therapy
treatments using the virus. The findings, published last week in The
Lancet, could dent the hopes of research groups who plan to use modified
herpes viruses to ferry beneficial genes into the brains of patients suffering
from brain tumours or Parkinson鈥檚 disease.
Ruth Itzhaki and her colleagues at the University of Manchester Institute of
Science and Technology examined brain tissues from 46 patients who died of
Alzheimer鈥檚 disease and 44 elderly people who died of other causes. As they had
expected, the researchers found that Alzheimer鈥檚 patients were more likely to
carry a gene known as &egr;4, a variant of a gene that makes a protein called
apolipoprotein E. The &egr;4 variant was already known to increase the risk of
developing Alzheimer鈥檚. But analysis of brain tissue from the patients revealed
a second risk factor: the presence of HSV1.
鈥淭he connection between the two was very strong, and in our Alzheimer鈥檚
samples, tissue from 53 per cent of the patients contained the virus and the
gene,鈥� says Itzhaki. In the Manchester team鈥檚 sample of patients, neither the e4
gene nor the virus alone seemed to increase the risk of Alzheimer鈥檚. But
together, they appeared to make a deadly combination.
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In the light of these results, suggests Itzhaki, the safety of gene therapy
using HSV1 should be reconsidered. She believes that the virus should not be
used in patients with the &egr;4 gene.
But gene therapists who intend to use HSV1 remain undaunted. 鈥淚t鈥檚 not going
to put us off,鈥� says Moira Brown of the Southern General Hospital in Glasgow,
who notes that HSV1, in a latent form, is found in the peripheral nervous system
of 80 per cent of the population. Brown plans to use HSV1 to introduce genes to
combat brain tumours. These patients face death if gene therapy is
unsuccessful.
David Latchman of University College London, who intends to use HSV1 variants
to treat Parkinson鈥檚 disease, says that larger studies are needed to confirm any
link between the virus and Alzheimer鈥檚. 鈥淚t鈥檚 an interesting piece of work, but
it would require much more work by other groups to establish a link,鈥� he
says.
Stephen Ingles, research director of Cantab Pharmaceuticals in Cambridge,
which also plans to use HSV1 in gene therapy, adds that in most proposals the
virus would be genetically 鈥渃rippled鈥� so that it cannot reproduce.