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ARRESTING ALZHEIMER’S
Drugs
that fight milder memory loss may prevent its onset. By Naomi Freundlich Business
Week. June 11, 2001 A new front has
opened in the battle against Alzheimer’s disease.
Coming up with a cure for this dreaded form of dementia has proven
devilishly hard, since by the time victims develop Alzheimer’s, their
brains are usually too damaged for any treatment to do much good.
So drug companies are increasingly turning their attention to a
different class of patients-those who suffer from noticeable memory loss
but otherwise function normally. The
theory is that treating patients with this condition, known as mild
cognitive impairment (MCI) might delay or deter full-blown Alzheimer’s.
MCI sufferers show no deterioration in IQ scores but they
experience “forgetfulness of a significant nature,” such as failing to
recall conversations held a short time before, says Dr. Ronald C.
Petersen, director of the Alzheimer’s Disease Research Center at the
Mayo Clinic in Rochester; Minn. This
is a more significant memory loss than forgetting a name or where you left
the car keys. Within six
years of a diagnosis for MCI, some 80% of such patients progress to
Alzheimer’s.
Consequently, the Food and Drug Administration has signaled its
willingness to overhaul its own criteria for judging brain-enhancing
drugs. On Mar.13, an FDA
advisory group ruled that experimental Alzheimer’s treatments can win
approval if they improve memory function in people with MCI, even if they
don’t alter the course of Alzheimer’s itself. This could mean a potential windfall for drug companies.
There are currently 4 million Americans suffering from MCI and
another 4 million with Alzheimer’s disease, says Vincent Simmon, CEO of
Cortex Pharmaceuticals Inc., a neuroscience company in Irvine, Calif.
Those numbers will go up as the baby boomers age.
In 2000, 35 million Americans were 65, and by 2025, there will be
63 million. Alzheimer’s
strikes about 10% of people over 65.
The National Institutes of Health is leading the way in MCI
research. In 1999, its
National Institute on Aging announced it would sponsor a three-year;
multicenter study over 700 MCI sufferers ranging in age from 55 to 90.
This trial is designed to see if Pzifer Inc.’s leading
Alzheimer’s drug, Aricept, or vitamin E, can delay the onset of
Alzheimer’s or other forms of dementia.
Other NIH-sponsored trials are testing estrogen and the popular
anti-inflammatory drugs that are known as cox-2 inhibitors for the same
purpose. If such treatments
can delay the onset of Alzheimer’s disease just for one year “it could
help between 220,000 to 440,000 people and save between $10 Billion and
$billion annually,” says Dr. Leon Thal, head of the Alzheimer’s
Disease Research Center at the University of California at San Diego.
It will be at least three years before the NIH trials produce
concrete results, and some scientists are already questioning the value of
the Aricept trial. “Pzifer
is dying to use Aricept on MCI,” says Harry M.Tracy, publisher of the
Newsletter NeuroInvestment. “But
there is a big question about whether it will work.”
The drug is one of three Alzheimer’s treatments on the market.
All of them block the breakdown of a brain chemical called
acetylcholine that is important in memory and other intellectual
functions. But there is no
proof the loss of acetylcholine plays as large a role in MCI as it does in
Alzheimer’s patients. And
these drugs aren’t even that effective against Alzheimer’s-they help
less than half of all Alzheimer’s patients, and then for a peiod of only
a few months or at most two years.
The problem, it seems, is that by the time a patient develops
Alzheimer’s the damage is done. The
disease is caused by a steady accumulation in the brain, over many years,
of an insoluble protein called beta-amyloid.
As it accumulates, it forms brain clogging plaque.
Victims eventually lose all mental and physical functions, until
they die, after about 10 to 12 years.
New drugs in the pipeline aim either to boost the brain’s ability
to form memories despite the plaque; or to slow the plaque buildup.
In the category are a group of drugs called ampakines, developed by
Cortex in partnership with the French company Servier, that increase the
activity of brain chemicals important to memory formation.
Cortex is testing one of its ampakines in a small study of
Alzheimer’s patients. The
company is planning a larger MCI trial with Servier for later this year.
Improved memory function is also the goal NeoTherapeutics Inc. in
Irvine, calif. Its lead
experimental drug, Neotrophin, stimulates the production and release of
growth factors in the brain’s memory centers.
These growth factors then coax neurons into making new connections
with other nerve cells. Neotrophin
has been tested more than 1,000 Alzheimer’s patients, with mixed
results. Still,
NeoTherapeutics President Rajesh C. Shrotriya says: “We believe that
Netrophin could have an effect in normal memory loss.”
Once the drug is approved for Alzheimer’s he plans to begin
testing it in patients with MCI. END RUN
The formation of memories, though, is a murky process.
As researchers in this field feel their way along, they are testing
a number of therapeutic approaches intended to aid the development of
memories. Memory
Pharmaceuticals Corp., a New York neuroscience company, is developing
drugs that will help the brain convert transient short-term memories into
stable long-term potentiation, is compromised in the aging brain and in
Alzheimer’s victims. Axel
Unterbeck, president of Memory Pharmaceuticals, says the company has
identified several promising drugs in hopes to start trials with
Alzheimer’s patients in two years.
Memory Pharmaceuticals is also trying to do an end run around the
disease, with experimental drugs that enhance the activity, and perhaps
the growth, of undamaged neurons in the brain’s memory centers.
This approach could have wide utility in treating memory problems
associated with dozens of diseases, including the normal forgetfulness
linked to aging. “It’s a
very important notion that even if companies succeed in prohibiting
amyloid production, the patient will still need treatment of memory
problems,” says Unterbeck. “We see using one drug that affects disease progression and
another that improves function and keeps the patient at home.”
Then there are the plaque-attackers.
Several groups are working on vaccines that would stimulate the
immune system to slough off the plaque deposits that lead to
Alzheimer’s. The leading
candidate is from Elan Corp. in South San Francisco.
In one test, Elan’s vaccine caused a 70% reduction in amyloid
plaques in the brains of mice genetically engineered to develop
Alzheimer’s. Elan, in
partnership with American Home Products, is now running early stage safety
trials of its vaccine in people with advanced Alzheimer’s disease.
“If the immunization works in Alzheimer’s patients, we will
move to MCI very rapidly,” says Dale B.Schenk, vice-president for
research at Elan.
Beyond vaccines are efforts by Bristol Myers Squibb, Eli Lilly, and
Elan to develop compounds that block the enzymes that help cause plaque.
Other drugs under development are likewise meant to interfere with
the process of plaque formation.
In three to five years, there may be more options for treating MCI
and new methods for slowing the onset of Alzheimer’s.
Researchers are also trying to devise ways of detecting who is at
risk for Alzheimer’s years before it becomes apparent.
In the end, the best chance of “curing” Alzheimer’s may be
targeting simple forgetfulness.
Copyright
© 2002 Global Action on Aging
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