The rodent testing from 2011 here: In 24 hours sounds pretty good.
https://www.jci.org/articles/view/46358
When systemically administered 24 hours after stroke, domain V was well tolerated, reached infarct and peri-infarct brain vasculature, and restored stroke-affected motor function to baseline pre-stroke levels in these multiple stroke models in both mice and rats.
Perlecan Domain V Therapy for Stroke: A Beacon of Hope?
The sad reality is that in the year 2012, people are
still dying or suffering from the extreme morbidity of ischemic stroke.
This tragedy is only compounded by the graveyard full of once promising
new therapies. While it is indeed true that the overall mortality
from stroke has declined in the United States, perhaps due to increased
awareness of stroke symptoms by both the lay public and physicians,
it is clear that better therapies are needed. In this regard, progress
has been tremendously slowed by the simple fact that experimental
models of stroke and the animals that they typically employ, rats
and mice, do not adequately represent human stroke. Furthermore, the
neuroprotective therapeutic approach, in which potential treatments
are administered with the hope of preventing the spread of dying neurons
that accompanies a stroke, typically fail for a number of reasons
such as there is simply more brain matter to protect in a human than
there is in a rodent! For this reason, there has been somewhat of
a shift in stroke research away from neuroprotection and toward a
neurorepair approach. (What goddamn wimps, just because something is hard is no reason to run away)This too may be problematic in that agents that
might foster brain repair could be acutely deleterious or neurotoxic
and vice versa, making the timing of treatment administration after
stroke critical. Therefore, in our efforts to discover a new stroke
therapy, we decided to focus on identifying brain repair elements
that were (1) endogenously and actively generated in response to stroke
in both human and experimental animal brains, (2) present acutely
and chronically after ischemic stroke, suggesting that they could
have a role in acute neuroprotection and chronic neurorepair, and
(3) able to be administered peripherally and reach the site of stroke
brain injury. In this review, I will discuss the evidence that suggests
that perlecan domain V may be just that substance, a potential beacon
of hope for stroke patients.
Keywords: Stroke, perlecan, neurogenesis, angiogenesis, neuroprotection, astrogliosis
Having a stroke, or any brain
injury for that matter, has the potential to rob us of what makes
us uniquely human. Whether the injury causes unilateral weakness,
an inability to speak or process language, or other severe morbidity,
the final outcome can profoundly reduce one’s quality of life.
Despite this sobering reality, our tools to combat ischemic stroke,
that kind of stroke caused by the blockage of a cerebral blood vessel
(typically from a blood clot/thrombus), are very limited. If a stroke
patient is “lucky” and they are quickly attended to
in a capable hospital environment, they may receive tissue plasminogen
activator (tPA) within a limited therapeutic window, measured in hours,
in an attempt to bust the blood clot causing the stroke, re-establish
blood flow to the affected brain area (which is not without its own
risks of reperfusion injury1,2), and potentially have
a good outcome. More recently, it has been demonstrated that tPA administered
after a so-called “wake-up” stroke, where a patient
has had a stroke while asleep and wakes up with stroke symptoms, may
be efficacious even when the exact time of stroke onset cannot be
pinpointed (the patient was asleep after all when the stroke occurred!).3 Of course, tPA is only effective if one suffers
a stroke due to a thrombus, which is the case about 85% of the time,
the remainder being due to bleeding in the brain (hemorrhagic stroke),
thereby necessitating that health care providers prove the type of
stroke, ischemic versus hemorrhagic, before tPA can be administered.
Furthermore, tPA carries the risk of so-called “hemorrhagic
transformation”, that is, causing a brain bleed, with potentially
lethal consequences (the risks and benefits of tPA therapy for ischemic
stroke are nicely reviewed in ref (4)). Finally, for exceptionally large clots that
tPA would not be able to completely lyse or when the therapeutic window
for tPA is missed, the option to mechanically retrieve the clot is
often available (review in ref (5)). Again, this runs the inherent risk of reperfusion injury
in a patient that is already hemodynamically unstable. Clearly, additional
and better stroke treatment options are needed.
No comments:
Post a Comment