“The results of recent
trials that tested much-anticipated Alzheimer's disease drugs dashed the hopes
of patients with the debilitating condition. The most recent disappointment
came from the large trial for solanezumab, by Eli Lilly, announced
last month.
“But experts across the field say hope is not lost. They believe
we will have some form of drug against the disease by 2025, albeit most likely
a pilot version that will need to be upgraded.
“This
target, in less than a decade, is the goal set by world leaders at the G8
dementia summit in 2013. Researchers believe there are enough competitors in
the race to get at least a few to the finish line on time. ‘There are still a
number of late-stage trials in progress,’ said Heather Snyder, senior director
of medical and scientific operations at the Alzheimer's Association. ‘2025 is a
realistic target in terms of where we are with the science. ... We're not off-track
at this point in time.’
“Twenty-four
drug candidates are currently in phase 3 trials on humans -- trials that
involve larger numbers of people and a comparator to see a drug's true effect
-- and many more potential drugs are in earlier stages of development. Speaking
from the Clinical
Trials on Alzheimer's Disease conference in San Diego this week, Snyder is
hopeful that a few drug options -- not just one -- may surface to one
day treat Alzheimer's at various stages of the disease.
“The
question now is, which trials will they be? Unlike with many other diseases,
scientists don't fully understand the underlying causes of Alzheimer's, meaning
drugs now in development are targeting different aspects of what is theorized
to cause symptoms. ‘This is a complex disease,’ Snyder said. ‘If you think of
HIV or cancer ... we don't treat those diseases with one drug.’ The end result
may have to be a combination therapy.
“It's
estimated that 46.8 million people were living with dementia worldwide in
2015, of which Alzheimer's disease is considered to be the leading cause. More
than 5 million people are
living with the condition in the United States.
“On Thursday, Biogen presented at the San Diego conference
and announced further promising results from its experimental drug aducanumab,
an antibody-based therapy, which saw significant reductions in amyloid plaques
in the brain of patients when compared against a placebo. This is one of three drug candidates in trials led by the company.
“More
than half of the drugs in current late-stage trials target these β-amyloid
proteins, which stick together to form plaques between nerve cells in the
brain's of Alzheimer's patients. The plaques destroy surrounding cells and
impair cognition.
“Drugs
reducing the existence of these plaques are one of the big goals to provide an
effective therapy, and Biogen's trial on patients with mild or pre-symptomatic
Alzheimer's disease saw a statistically significant reduction in these plaques,
as well as a slowing of mental decline, at the 12-month mark. This followed
strong results announced
earlier this year.
“‘It's
our most developed program in Alzheimer's disease,’ said Samantha Budd
Haeberlein, vice president of clinical development at Biogen. ‘The degree of
effect we had regarding the reduction of amyloid plaques ... was very exciting.’ The
drugs will soon enter into a new trial including almost 3,000 people across 20
countries to test the outcome on multiple populations. ‘It's a global clinical
trial,’ said Budd Haeberlein.
Budd
Haeberlein believes that targeting plaques is key to getting the first
therapies going, as the plaques appear in the brain up to 20 years before
symptoms begin. ‘It's important in reducing the impact of the disease,’ she
said.
“Another approach many in the field are picking as the
favorite in terms of potency to fight plaques in the brain is the use of drugs
known as BACE inhibitors, which block the production of an enzyme --
β-secretase -- needed for the production of β-amyloid proteins.
“By
blocking the production of the protein itself rather than killing it once it's
formed, it's hoped the impact could be more potent within the brain. ‘I think
BACE is a great target,’ said John Hardy, professor of neuroscience at
University College London in the UK, who first proposed that these
proteins, and plaques, were to blame for the development of Alzheimer's
disease. Twenty-five years after he first thought up the theory, he believes a
drug preventing their formation could be the winning formula. But Hardy worries
that drugs are being targeted at patients too late. ‘To attack amyloid
is to attack earlier,’ he said. ‘It might be being given too late.’
“One
of many companies testing this method is Eli Lilly. It hasn't let the failure
of its solanezumab drug hold it back. ‘We've seen that BACE inhibitors can
decrease amyloid protein production,’ said Dan Skovronsky, senior vice
president of clinical and product development at Eli Lilly. Its candidate in
this group, known only as AZD3293 for now, is in phase 3 trials and was bumped
ahead in the drug race this year. It was given fast-track designation from the US Food and Drug
Administration, which should help expedite its route to the market.
“Although they may be talked about more often, plaques are
not the only theory among scientists to explain how Alzheimer's disease occurs.
Another suspect thought to play a key role is a protein known as tau, which
forms tangles inside cells in the brain. The twisted tangles are thought to
block the transport of nutrients in cells, causing them to die. But these are
formed much later in the disease than the plaques, resulting in faster
cognitive decline. ‘Tangles
actually spread across the brain,’ said Skovronsky, whose colleagues at Eli
Lilly have developed imaging technologies to identify their presence inside the
brain. ‘Our aim is to block their spread ... but it's been more difficult to
attack the tangles.’
“Two
of eight drugs Eli Lilly has in development are targeting these tangles
inside the brain. ‘We didn't have a way of seeing them until now,’ he said. ‘(They)
develop later, and as people progress through the disease, they get more
tangles.’ The Alzheimer's Association's Snyder believes the tangles are an
important target for effective drug therapies, as they act as a better
predictor of dementia symptoms.
“A
drug recently trialed to bust these tangles was LMTM, by TauRx pharmaceuticals.
It failed to reveal significant benefits to patients, but a small group did see
improvements in cognitive testing, meaning all was not lost. Presenting
at the conference on Thursday, the company announced it was conducting trials
specific to populations that are most likely to benefit -- in this case,
patients with mild or probable Alzheimer's disease. ‘We're hoping for
optimistic results coming out of these trials,’ said Snyder.
“But
Hardy is not so optimistic, believing that although tau proteins are a good
target, this is not the drug to do the job. ‘Tau is the right target ... (but)
that's a terrible drug,’ he said, questioning the approach of bursting the
tangles apart.
With
so much in the pipeline, two points are clear: There is unlikely to be one drug
that will beat Alzheimer's in all patients affected, and the aging population
around the world means a greater number will need them once they become
available.
“‘We
will still see millions with the disease ahead. ... It might be then, that in
the future, we need to target multiple therapies,’ Skovronsky said. ‘We're not
giving up on Alzheimer's patients, that's for sure.’”
from Mary Richie:
ReplyDeleteYes, I know that the pundits think they might soon find a pill that might work to combat the onset of Alzheimer's. They continue to approve of a varied lifestyle that I'm trying to follow, a diet full of a variety of foods, including seasonal fruits and vegetables, physical exercise, intellectual stimulation, and a wide variety of socialization.
The researchers testing me yearly as part of the Rush Alzheimer’s study also spend a considerable amount of time questioning to see whether I've remained having a positive outlook on life in general. With this recent national election many of us find it hard to remain positive, but researchers studying Alzheimer’s believe that those managing to maintain a positive attitude manage to resist dementia longer.
Let's try to remain positive. Let's sit back and watch how the republican legislators who thwarted Obama most every step of the way for the last eight years deal with this "republican" president.
Mary