Alzheimer's treatment makes mice brains bleed
Immunization used in halted human
trial may weaken blood vessels.
15 November 2002
JOHN WHITFIELD
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| Alzheimer's attacks blood
vessels, as well as brain tissue. |
| © SPL |
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Immunizing mice against a condition akin to Alzheimer's
disease makes their brains prone to bleeding, researchers have
found1. This hints at why cerebral
inflammation halted an experimental human vaccine trial early
this year.
The link between mouse and human symptoms is still unknown.
But both probably stem from the effects of immunization on
damaged blood vessels, says the study's leader, Mathias Jucker
of the University of Basel, Switzerland.
"These findings are pretty bad for the vaccine," comments
neuroscientist Christian Haass of Ludwig Maximilians University,
Munich, Germany. "The bleeding is terrible - it could be
deadly."
The results suggest that immunization may be more suited to
protecting healthy brains than curing diseased ones. Another
possibility would be to screen patients for vulnerable blood
vessels before vaccination.
But other Alzheimer's experts believe that the different
symptoms and side-effects in mice and humans make it impossible
to connect this research with the trials. "It would be a giant
leap to apply this to an Alzheimer's patient," says Roger Nitsch
of the University of Zurich, Switzerland.
This is the first time that bleeding has been seen in any
animal or human test of Alzheimer's therapies. "We've never seen
anything like this - and we've looked hard for it," comments
Dale Schenk, head of research at Elan Pharmaceuticals of South
San Francisco, the company behind the trial vaccine.
The mice that Elan use to study Alzheimer's do not have
damaged blood vessels, Jucker counters - so one would not expect
immunization to affect them in this way.
Despite the setback, Alzheimer's researchers are still
optimistic about the prospects for immunization. Most agree that
more results are needed from humans for us to truly understand
immunization's effects. Follow-up studies and post mortems of
the 375 people immunized in the aborted trial should still give
us invaluable information.
Beta test
The brains of Alzheimer's sufferers contain deposits of a
protein called amyloid beta. These are thought to relate to the
brain damage and dementia that are symptomatic of the disease.
Three years ago, researchers at Elan proposed that injecting
amyloid beta into the blood triggers an immune response that
fights the disease. No one is yet sure how this works.
Tests were spectacular in mice engineered to develop a form
of Alzheimer's. Amyloid deposits shrank, and the animals'
memories improved. The vaccine was made from a synthetic version
of amyloid.
But trials in Alzheimer's sufferers were halted in January,
when some patients developed symptoms similar to meningitis and
encephalitis. The new finding suggests how this may have come
about.
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It would be a giant leap to apply this to an
Alzheimer's patient
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Roger Nitsch
University of Zurich
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Jucker and his colleagues injected elderly mice with
antibodies against amyloid, rather than amyloid itself. Five
months later, the mice had smaller deposits of the protein in
their brains. But they also had many small haemorrhages in
cerebral blood vessels.
The mice - and most human Alzheimer's patients - have amyloid
deposits in the brain's blood vessels, as well as its tissue.
Clearing out the protein might weaken these vessels.
Vaccinating people before they get Alzheimer's, or in the
very early stages of the disease, might help, as amyloid would
not have had time to build up, says Richard Harvey, research
director of Britain's Alzheimer's Society.
But if immunized human patients bled, it is surprising that
none of them had a stroke, Harvey adds. "I doubt that the
bleeding is the whole story". Bleeding may be a second
side-effect to put alongside inflammation, agrees neuroscientist
Dave Morgan of the University of South Florida. |
