This points out the complete lack of stroke leadership. Leaders would take these promising ideas and run them to completion. My god, do we have incompetency in stroke, 6 years and nothing seems to have happened.
What happened to this?
Safety and efficacy of NA-1 in patients with iatrogenic stroke after endovascular aneurysm repair (ENACT): a phase 2, randomised, double-blind, placebo-controlled trial October 2012
Is this enough to push out to all stroke hospitals?
Who is going to do that? I want a name.
The future of stroke patients may depend on the part-time job of a Canadian surgeon
There are roughly 100 billion neurons
in the human brain.(Wrong, 80 billion) These microscopic cells transmit and process
information we receive from the outside world and turn our thoughts into
action. They are responsible for how we talk, how we move, and how we
think. Neurons are, in many ways, what make us us.
Strokes
kill neurons. By starving them of the blood that carries glucose and
oxygen, strokes trigger a biochemical cascade that destroys neurons in
vast numbers. Ischemic strokes—the most common form, caused by a blocked
blood vessel—kill an average of 1.9 million neurons for every minute
the patient is untreated. Those dead neurons add up, and in 10 hours,
stroke patients can lose as many neurons as they would in 36 years of normal aging.
Roughly
15 million men, women, and children suffer strokes every year, and
about half of them are fatal.(1/3 are fatal) Stroke is the second-leading killer
globally, after its close cousin, heart disease, and far more deadly
than cancer and the most life-threatening communicable diseases like
AIDS and malaria.
| Global Rank | Cause | Deaths (millions) | % of total deaths |
|---|---|---|---|
| 1 | Ischemic heart disease | 9.43 | 16.6 |
| 2 | Stroke | 5.78 | 10.2 |
| 3 | Chronic obstructive pulmonary disease | 3.04 | 5.3 |
| 4 | Lower respiratory infections | 2.96 | 5.2 |
| 5 | Alzheimer’s disease and other dementias | 1.99 | 3.5 |
| 6 | Trachea, bronchus, and lung cancers | 1.71 | 3.0 |
| 7 | Diabetes | 1.60 | 2.8 |
| 8 | Road injury | 1.40 | 2.5 |
| 9 | Diarrheal diseases | 1.38 | 2.4 |
| 10 | Tuberculosis | 1.29 | 2.3 |
Source: World Health Organization (2016)
Yet
despite the enormous toll of stroke, the pharmaceutical industry has
been virtually powerless to treat it. After decades spent pouring
billions of dollars into the pursuit of drugs to protect neurons after
strokes without success, most drug companies abandoned the field by the
mid-2000s.
Today, fewer than 5% of all stroke
victims worldwide receive any treatment beyond basic palliative care,
and the lack of effective stroke drugs remains one of the most glaring
unmet needs in medicine.
Stroke is a
maddeningly complex problem. The intricacy of the brain, the need for
immediate action, and the variability of both strokes and the people who
have them make designing and testing drugs an enormous challenge. But
the medical establishment has failed stroke patients not just because
the research is hard, but because of misaligned incentives, the
financial pressures of an industrial drug-development model, and sloppy
science.
Stroke nihilism
“Time is brain” is a longtime cliche among stroke professionals, but it’s largely true.
Death
follows when a stroke causes the brain to swell, starving it of oxygen,
or because the stroke destroys the body’s ability to regulate breathing
or blood flow. Others die from complications like pneumonia, which can
affect up to one-third of all stroke patients. Stroke weakens the immune system,
making it harder for the body to fight lung infections that can occur
when stroke victims, who can no longer swallow properly, wind up with
food, water, or saliva in their lungs.
For
most of history, health workers had no way to help stroke victims. Once a
stroke was identified, the patient was made comfortable and family
members were given the bad news. Stroke was viewed as a dead end—for
patients, for researchers, and for neurologists looking for
solutions—and stroke nihilism still permeates the medical establishment.
The
bulk of progress in reducing stroke deaths has come from prevention,
particularly the introduction of medicines to lower high blood pressure,
a leading cause of stroke.
The first—and to
date only—medical breakthrough for stroke treatment came when a drug
called tissue plasminogen activator (tPA, sold globally under the brand
names Activase and Actilyse) was approved by the US Food and Drug
Administration (FDA) in 1996.
The goal of tPA
is “reperfusion,” the act of returning blood flow to the injured part
of the brain. While neurons in the immediate vicinity of the stroke
can’t be saved, there’s a larger zone, called the ischemic penumbra,
that can be rescued if blood flow can be restored. The longer the
penumbra is deprived of blood, the less brain there is to save.
With
tPA, emergency-room doctors at last had a way to treat patients. But,
as with most things in the world of stroke, there were complications.
In
this case, the issue was that there are two kinds of stroke. While the
majority (about 85% in the US) are ischemic and caused by a blockage
that can potentially be treated with tPA, the rest are hemorrhagic,
caused by a ruptured blood vessel, and tPA can be be fatal in these
strokes because it prevents the blood from clotting. (For that reason,
the drug is also not given to patients on blood thinners or who have
other complications. As many as 65% ischemic stroke patients are not eligible for tPA).
Doctors
can’t administer tPA without determining the nature of the stroke and
that can only be done by examining the brain with a CT scan or some
other advanced brain-imaging device. There are less than 4.5 hours after
the onset of stroke for doctors to administer the drug—in many cases,
not nearly enough time for a patient to get scanned. For patients over
80 or those who had a previous stroke, the window is only three hours.
Read more: With the pharma industry’s repeated failures to develop stroke treatments, stroke doctors have turned to mechanical devices that can clear blocked blood vessels in the brain.
Further,
tPA is expensive. The drug, developed by Genentech, has no generic
competition, and a 100 milligram vial used in a typical treatment can
cost more than $8,300.
It also needs to be refrigerated, a challenge for clinics in some parts
of the world. As a result, the use of tPA is limited to affluent
nations with sophisticated healthcare systems, and even then it is only
rarely administered. Since its introduction, tPA has also been plagued by doubts about its safety,
stemming from long-standing criticisms of its initial clinical trials.
As a result, some doctors won’t prescribe it, even in eligible patients.
Fewer than 5% of patients diagnosed with ischemic stroke in the US
received the drug, according to a 2014 study. In poorer parts of the world, the number is closer to zero.
Despite tPA’s limited reach, it’s enormously profitable, estimated to make $1.5 billion (pdf) in revenue this year for Roche, the Swiss pharma giant that owns Genentech.
“The lesson they learned is that they should pursue something else.”
Given
tPA’s limitations—and the enormous potential market—researchers have
focused on finding a drug that preserves neurons until the brain is
reperfused. These drugs, called “neuroprotective agents,” could either
save the brain cells in the penumbra until the brain heals, or extend
the window of time to preserve neurons in stroke patients until a clot
is dissolved by tPA or removed with a mechanical device. In theory, a
neuroprotective drug that could be given safely to the 15 million
victims of ischemic and hemorrhagic stroke each year—and that
could be administered without scanning them first—could generate many
times tPA’s revenues.
Jeffrey Saver, a
University of California-LA neurologist at the forefront of stroke
research for decades, calls neuroprotection the “Holy Grail” of stroke
treatment, and like that sacred relic, its pursuit has been an epic tale
of frustration and failure.
According to one landmark study, 1,026 potential neuroprotective drugs were tested between 1957 and 2003, in 8,516 separate experiments. Researchers experimented with aged-garlic extracts, uric acid, and compounds engineered from pigs’ brains.
Their trials have alluring names, built out of complicated acronyms,
that suggest important science is taking place: VENUS, ACTION, SAINT.
None worked.
Those
failures cost billions of dollars and wasted the productive years of
thousands of scientists. Worse, they salted the ground for future
research, ushering in what one researcher called “the nuclear winter”
for neuroprotection research. The pharma industry saw more lucrative
opportunities elsewhere, and moved on.
“Sadly,
the lesson they learned is that they should pursue something else,”
says Myron Ginsberg, a neurologist at the University of Miami who has
studied the industry’s failures.
But not all
scientists accepted that conclusion. On the fringes of industrial
medicine, one neurosurgeon has spent the last two decades doggedly
developing a neuroprotective agent.
The great white north of neuroscience
The
best hope for stroke patients may come not from the giant research labs
of industrial pharma, or the biotech hotbeds of Boston or San
Francisco, but from the relative backwater of Toronto, Ontario.
Michael
Tymianski, now 55, has been working on his drug, called NA-1, since the
late 1990s, when researchers were still infused with optimism about
developing a stroke treatment. A tall, balding man with a furious work
ethic, Tymianski poured himself into developing NA-1 while holding down
his day job as a neurosurgeon at a Toronto hospital. His plan was always
to develop the drug to the point where it could be tested in humans,
then sell it to a pharma company. But no buyers materialized, and
eventually Tymianski stopped looking.
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