Meet The Real Heroes Of The Fight To Treat Alzheimer’s – BuzzFeed News


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Abbi Fox at her home in
Tiburon, California, on Dec. 21. Brian
L. Frank for BuzzFeed News

ID: 10222015

“Can you get me tickets for Hamilton?” Abbi Fox, until
recently a realtor
selling swanky homes in Marin County, north of San Francisco,
knows how to break the ice.

Her opening gambit instantly dissolved any tension about
talking over what for months she dodged discussing with even
her closest friends. Abbi had known that something was wrong
when her memory started to fail. Today she has been diagnosed
with a condition called mild cognitive impairment, and is
enrolled in a clinical trial of a drug for Alzheimer’s disease.
And that places Fox, 72, and her family on the front lines of
the fight against the leading cause of dementia.

“Abbi didn’t want to talk about it with anyone,” explained her
husband, Rob, when I met with the couple a few days later. He
recalled fielding calls from anxious friends. “When she’s
ready, she’ll talk about it,” he told them.

Abbi mustered the courage to send her friends an email
explaining her condition a few months ago. “The reaction has
just been amazing,” she said. “I happen to have an amazing
group of lady friends. And my two daughters and my husband.
They are all so supportive.”

She is in a clinical trial for aducanumab,
being tested by the biotech firm Biogen of Cambridge,
Massachusetts. The
drug attacks a protein called amyloid-beta, which builds up
in the brains of people with Alzheimer’s disease. This buildup
is thought to trigger a cascade of problems that lead to
dementia.

Aducanumab is one of a handful of experimental drugs that
biomedical scientists hope will not just alleviate symptoms,
but also slow the disease’s progress.

Days before BuzzFeed News first spoke with Abbi, however,
another of these drugs — called solanezumab
or “sola” — had hit the headlines, for the wrong reasons. “Eli
Lilly’s Experimental Alzheimer’s Drug Fails in Large Trial,”

wrote the New York Times.

News reports discussed what the failure meant for scientists’
understanding of Alzheimer’s, a disease that has proved far
more complicated than once thought, and looked at the prospects
for other drugs in the pipeline. Others framed the story as a
huge business blow for the pharma giant Lilly — its shares lost
10% of their value overnight.

Few spoke about the families grappling with the erosion of
their loved ones’ minds, or to the patients who have
volunteered to take part in clinical trials. Yet without them,
there will never be an effective treatment, however brilliant
the scientists involved, and however determined Big Pharma is
to find the next blockbuster drug.

Abbi’s diagnosis of mild cognitive impairment is
described by the Mayo Clinic as an “intermediate stage
between the expected cognitive decline of normal aging and the
more-serious decline of dementia.” Not everyone who gets this
diagnosis goes on to develop Alzheimer’s disease. But many,
sadly, do.

Abbi is now a volunteer in the war against Alzheimer’s because
of a sobering realization that doctors had in the last decade:
By the time dementia sets in, the damage that has accumulated
in the brain is at an advanced stage, and may be impossible to
reverse. Scientists now think that the best hope of making a
real difference lies in intervening early, as soon as problems
start to emerge — or even before, for people with a family
history of dementia that places them at high risk.

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PET scans can detect the
proteins that build up in the brains of people with
Alzheimer’s disease. Evan
Vucci / AP Photo

ID: 10222032

Abbi knew that something was wrong more than a year ago when
she started struggling with the legal paperwork for her real
estate deals. “I was not happy to give it up,” she said,
sitting with Rob in their living room. “It was the definition
of who I am.”

There was a weekly rhythm. Each Monday she would pull all the
new ads and match listings to the requirements of her wealthy
clients. Later in the week, she’d meet other realtors over
lunch and shoot the breeze. Abbi knew that she couldn’t stay in
the business. “These people were relying on me to buy $2 or $3
million homes,” she said. “I could screw it up for the person
I’m buying for.”

Rob had already begun to notice that Abbi was having problems
with her short-term memory — for example, repeatedly offering
more vegetables when family or friends gathered for a meal.

As Rob explained about his wife’s symptoms, my mind flashed
back to my initial telephone conversation with Abbi. During a
brief pause, as I caught up with my note-taking, Abbi had
stepped in to jog things along: “Can you get me tickets for
Hamilton?”

“I wish that I could,” I quickly replied, not wanting her to
notice that I’d been thrown by being asked the question again.
(When we talked about it later, Abbi teared up, agreeing that
the repetition was a symptom of her condition.)

Forced retirement was dispiriting enough, but Abbi’s first
encounter with a medical specialist was devastating: “He was
this rude, hideous man.” When Abbi mentioned that she wanted to
take her two grandchildren to Paris, the doctor said, “You’d
better hurry up and do it.”

“He had no bedside manner,” Rob observed.

When she got home after the consultation, Abbi was
hyperventilating. Her youngest daughter, Marcy, said, “Mom,
he’s an idiot.” So Abbi went back to her primary care doctor,
and was referred to the Memory and Aging Center at the
University of California, San Francisco, where she had a much
better experience. Staff at the center broached the possibility
of joining a clinical trial.

Abbi and Rob came home with reams of paperwork describing the
clinical trials recruiting patients at the UCSF center —
typically there are eight to ten trials enrolling at any time.

Some, like the Biogen trial that Abbi opted for, are massive
“phase 3” trials running at dozens of medical centers
worldwide. These are the make-or-break, final stage of testing,
needed to show whether a drug actually works well enough to win
approval from the Food and Drug Administration as a new
treatment. (Eli Lilly’s disappointing announcement about sola
came after it failed to meet its goals in another phase 3
trial.)

Patients learn the goals of the research before enrolling, and
then are told to go away and digest the informed-consent
documents at their leisure. “I call it the period of
contemplation,” Mary Koestler, clinical trials coordinator at
the UCSF Memory and Aging Center, told BuzzFeed News. Potential
volunteers can’t be put under any pressure to take part — and
are also free to withdraw from a trial at any point if they
decide it’s not for them.

Even after volunteering to test an experimental Alzheimer’s
drug, there’s no guarantee that you’ll be accepted. First come
exhaustive cognitive and medical tests to make sure that
patients meet the inclusion criteria. For Abbi, these included
a spinal tap, an MRI, and a special type of PET scan that can
actually detect amyloid-beta in the brain.

Abbi did meet the criteria, and now makes monthly visits to
UCSF for a one-hour infusion of what might be aducanumab — or
might be an inert placebo. Neither Abbi nor any of the clinical
trials staff at UCSF are allowed to know whether she’s on the
active drug, as part of the rigorous “double-blind” procedures
required for phase 3 clinical trials.

While sola and aducanumab both target amyloid-beta, they work
in different ways. Sola was supposed to mop up the protein from
the blood, while aducanumab attacks “plaques” of amyloid-beta
that build up in the brain. So there’s reason for optimism in
that difference, despite sola’s failure: In August, a
paper in the science journal Nature reported that
aducanumab reduced amyloid-beta plaques in the brains of 165
patients in the early stages of Alzheimer’s disease. It also
seemed to slow their cognitive decline — although there weren’t
enough patients to make a statistically definitive judgment on
that.

Now Biogen is running
two phase
3 trials, which will involve 2,700 patients and bring the total
cost of developing the drug, together with investment in
manufacturing, to
some $2.5 billion.

Drug development is a long haul. Results from Biogen’s phase 3
trials aren’t expected until 2020. If aducanumab disappoints,
then hope will shift to drugs in earlier stages of development
that target another brain protein called tau. In the brains of
people with Alzheimer’s, tau forms tangles that are toxic to
nerve cells.

Volunteers in Biogen’s trials must be watched closely. Despite
the positive results so far, 27 of the patients in the trial
published in August developed brain swelling, and 12 were taken
off the drug. But Abbi has had no ill effects, and enjoys her
trips to UCSF with Rob. “It’s our date day,” she said. “We get
lunch.”

It’s the cognitive assessments, which must be given every few
months to monitor her progress, that Abbi finds burdensome and
somewhat humiliating. These involve pencil-and-paper tests and
verbal tasks like counting backward in nines from 100. Many
volunteers dislike the tests, Cynthia Barton, a nurse
practitioner on the UCSF clinical trials team, told BuzzFeed
News: “It’s not always easy to do two hours of cognitive
testing that you’re not very good at anymore.”

Still, there are benefits to being enrolled in a clinical
trial, not least the extended contact with nurses and doctors
that isn’t part of everyday medical care. For patients with
only basic medical insurance, that’s especially welcome. But
for everyone, including caregivers like Rob, it eases the
pressure.

“You can’t undervalue the burden that some caregivers are
under,” Adam Boxer, a neurologist who heads the UCSF clinical
trials team, told BuzzFeed News. “Not just the amount of time
and physical effort they put into it, but just emotionally.”

View this image ›

Abbi Fox with her husband, Rob,
at their home in Tiburon, California, on Dec. 21.
Brian
L. Frank for BuzzFeed News

ID: 10222035

For William and his wife Barbara — not their real names — the
stigma associated with Alzheimer’s disease is such that they
only agreed to be interviewed for this article on condition of
anonymity. William, aged 68, is a retired surgeon who is also
enrolled in one of Biogen’s aducanumab trials. As a former Army
reservist in the Medical Corps, William said that he applies
the military doctrine of “need to know” to his condition.

“I don’t need to stand on the rooftop and shout it to the
neighborhood,” he told BuzzFeed News.

But William’s biggest concern is that going public might create
problems for his younger family members. He was one of 12
siblings, and dementia runs in the family. All five sisters,
and all but one brother, have been affected. William’s current
diagnosis is mild cognitive impairment, but he is realistic
about what probably lies ahead. “It has a high propensity to
progress,” he said.

William has good reason to be worried about the consequences of
revealing a family history of Alzheimer’s for relatives who are
still at work. That’s usually where the earliest signs of the
condition get noticed. A public diagnosis is often a
career-ender, and no one wants to be under a spotlight, with
their bosses looking for the first hints of mental decline.

Even if they aren’t looking for signs of dementia, human
resources departments can create distress for employees
beginning to experience symptoms. Barton, the UCSF nurse
practitioner, said that patients can have the humiliating
experience of being counseled for substance abuse — another
common cause of sudden problems with job performance.

As a medical man, William went into the Biogen trial with his
eyes wide open. “There are advantages and disadvantages to how
much you know about something,” he said. While he holds hope
that aducanumab may help him, he also knows that drugs can fail
in clinical trials.

Abbi and Rob, meanwhile, hadn’t given much thought to the
possibility, until the news about Lilly’s sola trial broke on
Nov. 23. “It hit me really hard,” Rob said. “What if someday we
get a phone call …”

In reality, that isn’t how these things work. Nobody in the
sola trial got a call. Neither did Boxer, even though he was
one of the senior doctors running the trial. Instead, reporters
and Wall Street investors were the first to know, when Lilly
put out a
press release.

This is unavoidable, Lilly spokesperson Nicole Hebert told
BuzzFeed News by email, adding that the company did post an

online video to thank research volunteers.

“Manufacturers like Lilly are not allowed to have direct
communication with clinical trial participants,” Hebert said,
adding that communication must go through the lead researchers
at each trial site, and be run through a local ethics board.
“As you can imagine, this can take time and is not a practical
way of delivering a timely message,” she said. Companies must
also avoid early leaks of information about clinical trial
results to avoid the risk of insider trading.

But getting the news secondhand adds to the blow. William and
Barbara are members of separate support groups, for patients
and caregivers respectively. Barbara’s includes two men whose
wives were enrolled in the failed sola trial. One was watching
CNBC, and noticed a sudden drop in Lilly’s stock price flash
across the screen. He went online to find out what had
happened, and learned that the drug his wife was taking had
failed its big test.

One of the two men couldn’t bring himself to tell his wife what
had happened — and just said that doctors had decided to
discontinue the drug. The other man’s wife cried when she
learned the news. “He said his wife enjoyed going to get the
infusions. She thought it was helping her,” Barbara told
BuzzFeed News.

“It’s a tough thing,” William said.

When an experimental drug fails, clinical trials staffers at
UCSF face the difficult task of discussing volunteers’ options.
Some want to sign up for another trial. But that isn’t always
possible — their condition may have progressed to a point where
they no longer meet the eligibility criteria for the trials
that are recruiting.

Most painful, for Boxer, is that some patients decide to
purchase unproven “brain supplements” advertised online. “At
some point one becomes desperate enough that one becomes
susceptible to these charlatans peddling snake oil,” he said.
But he understands the perspective of patients: “The best of
scientific medicine hasn’t got me very far.”

Despite the disappointments of past trial failures, and the
knowledge that experimental drugs may come with unknown risks,
as well as uncertain benefits, William said he was determined
to keep following the scientific path.

“I have no change at all in my feeling about the importance of
clinical trials,” he said. “It’s just not in my nature to give
in.”



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