Comparative Efficacy of Neuroprotective Agents for Improving Neurological Function and Prognosis in Acute Ischemic Stroke: A Network Meta-Analysis

 First of all, stop using the term, neuroprotection! Neuronal cascade of death is the correct term! It gives absolutely NO SENSE OF URGENCY! If you tell your patients, you know nothing about stopping  the 5 causes of the neuronal cascade of death in the first week thus letting die hundreds of millions to billions of neurons.  They might just get angry with your incompetence!

Send me hate mail on this: oc1dean@gmail.com. I'll print your complete statement with your name and my response in my blog. Or are you afraid to engage with my stroke-addled mind? I would like to know why you aren't solving stroke to 100% recovery, because this doesn't solve stroke recovery at all!

You'll have to ask your competent? doctor why the hell edaravone is approved in Japan since 2001 but not the US.

Has your stroke hospital done anything with any of these in the last decade? OR ARE THEY COMPLETELY FUCKING INCOMPENT AT EVERYTHING IN STROKE? 

 You can easily see how much research is out there to be implemented and your hospital is totally incompetent if not done. 

• Cerebrolysin (12 posts to June 2014)
• citicoline (15 posts to October 2011)

• minocycline (17 posts to May 2012)

• dl-NBP (1 post to April 2017)
• 
  
• NA-1 (5 posts to October 2012) 

• edaravone (12 posts to November 2011)

• Role of vinpocetine in ischemic stroke and poststroke outcomes: A critical review 2020

• Anti-inflammatory effects of vinpocetine in atherosclerosis and ischemic stroke: a review of the literature 2014

• A systematic review of vinpocetine therapy in acute ischaemic stroke 1999

• Vinpocetine inhibits NF-κB-dependent inflammation in acute ischemic stroke patients 2018

The latest here:

Comparative Efficacy of Neuroprotective Agents for Improving Neurological Function and Prognosis in Acute Ischemic Stroke: A Network Meta-Analysis

Yuchen Wang ^1,2 Mengqi Li ^1,2 Yuye Jiang ^1,2 Qiuhong JI ^1*

• ¹ Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China
• ² School of Medicine, Nantong University, Nantong, Jiangsu Province, China

The final, formatted version of the article will be published soon.

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cause of combined disability and mortality globally. While reperfusion therapies play a critical role in the management of acute ischemic stroke (AIS), their applicability is limited, leaving many patients with significant neurological deficits and poor prognoses.Neuroprotective agents have garnered attention for their potential as adjunct therapies; however, their relative efficacy remains unclear. This study utilized a network metaanalysis (NMA) to systematically compare the efficacy of neuroprotective agents in improving neurological function and prognosis in stroke patients. Methods: This study adhered to PRISMA guidelines and the Cochrane Handbook for systematic reviews. Randomized controlled trials (RCTs) were identified through comprehensive searches of the PubMed, Embase, and Cochrane Library databases. Two independent reviewers conducted the selection process, data extraction, and quality assessment. Outcomes included 90-day modified Rankin Scale(90d-mRS)、change of National Institutes of Health Stroke Scale score from baseline to 90-day/14-day/7-day (90day/14d/7d-NIHSS) and 90-day/14-day Barthel Index (90d/14d-BI).Data analyses were performed using RevMan 5.4 and Stata 14.0. Results: A total of 42 RCTs involving 12,210 participants were included in this analysis. The interventions assessed included Cerebrolysin, Citicoline, Edaravone, Edaravone Dextranol, HUK, Minocycline, NA-1, NBP, Vinpocetine, and Control. The NMA results demonstrated that NBP ranked highest for the 90d-mRS, 90d-NIHSS, 14d-NIHSS, and 14d-BI outcomes. Edaravone was found to be the most effective intervention for the 7d-NIHSS and 90d-BI outcomes.The findings of this study indicate that different neuroprotective agents exhibit distinct advantages at specific stages of recovery. NBP showed outstanding performance in improving 90d-mRS and 90d-NIHSS, underscoring its potential in long-term rehabilitation. Edaravone demonstrated significant superiority in 7d-NIHSS scores, highlighting its role in early neuroprotection. These results provide valuable insights for individualized clinical treatment. To further validate the efficacy and safety of neuroprotective agents, future studies should involve larger sample sizes and conduct multicenter, large-scale randomized controlled trials.

Keywords: Neuroprotective Agents, Network meta-analysis, n-Butylphthalide, Edaravone, Neurological function, stroke rehabilitation

Received: 19 Nov 2024; Accepted: 13 Dec 2024.

Copyright: © 2024 Wang, Li, Jiang and JI. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.   

What Golden Hour for Stroke? Introducing the 'Platinum Half-Hour'

Wrong,wrong, wrong. This research on mice suggests you have 3 minutes to get fully recovered. Let's see you meet that goal. And since that is impossible you'll have to stop the 5 causes of the neuronal cascade of death in the first days saving billions of neurons, vastly reducing your 30-day death rate and making your rehab much more likely to succeed. 

In this research in mice the needed time frame for tPA delivery is 3 minutes.

Electrical 'storms' and 'flash floods' drown the brain after a stroke

The latest here:

 

What Golden Hour for Stroke? Introducing the 'Platinum Half-Hour'

Higher stakes for a neuroprotectant to be found someday

by Nicole Lou, Senior Staff Writer, MedPage Today May 13, 2022

Researchers have upped the ante on the "golden hour" concept in stroke with their finding that ultra-early stroke intervention is a reachable target.

The FAST-MAG trial, originally designed to test magnesium as a neuroprotective agent, had 12.1% of 1,680 stroke patients treated by paramedics within 30 minutes of the time they were last known to be well, according to Fatima Pariona-Vargas, MD, of Peru's National University of Cajamarca School of Medicine, and colleagues.

Magnesium administration within this "platinum half-hour" did not result in better 3-month functional outcomes. "However, once a beneficial therapy able to be started in ambulances becomes available, platinum half hour treatment is likely to be associated with maximal intervention benefit," the authors argued in their paper in Stroke.

Given the precious minutes spent waiting for EMS to arrive on the scene and transport the patient, prehospital treatment is probably the only practical way to employ stroke interventions within the platinum half-hour, the researchers acknowledged.(So if your hospital touts their door to needle time, they don't understand the actual time needed.)

The 12.1% rate of treatment within 30 minutes by the FAST-MAG paramedics is "very impressive," said James Grotta, MD, a vascular neurologist at Memorial Hermann Health System and director of the Houston Mobile Stroke Unit.

"The study underscores the importance and potential value of moving treatment into the prehospital setting," he told MedPage Today.

Neuroprotective agents would theoretically fit the bill for safe, ultra-early prehospital treatment of hemorrhagic and ischemic strokes alike. The hope is that the agents would allow regular ambulances to skip the imaging required to distinguish between the two when applying intravenous (IV) thrombolysis and other treatments.

A good neuroprotectant might buy rescuers more time for other therapies once they confirm that the patient has a hemorrhagic or ischemic stroke, said stroke neurologist Tudor Jovin, MD, of Cooper Medical School of Rowan University in Camden, New Jersey, in an interview.

Yet researchers have failed, time and time again, to identify a good agent.

NA-1 is one neuroprotectant still currently under investigation in the FRONTIER trial.

Although FAST-MAG had failed to show efficacy for prehospital IV magnesium ≤2 hours of stroke onset, magnesium, being a glutamate antagonist, might still have neuroprotective effects revealed if administered very early and studied in a larger sample, Grotta suggested.

So is this trying to say that magnesium might tackle one of the 5 causes of the neuronal cascade of death

As for speedy reperfusion therapy, he said that tenecteplase (TNKase) shows promise for fast administration -- perhaps feasible in the first 30 minutes.

"I think that in acute stroke treatment, we're entering a new era where these kinds of approaches are becoming feasible," Jovin said.

He noted that besides prehospital therapies, there also needs to be faster detection of stroke in the field. To that end, devices are being developed to detect strokes when they happen. "That's something we used to think was science fiction. It looks more and more like reality -- not yet in wide use, but hopefully soon," he said.

Pariona-Vargas and colleagues had conducted an exploratory analysis of the phase III FAST-MAG trial.

Study participants had a median age of 69 years, and the group included approximately 45% women. Patients scored a median 4 on the prehospital Los Angeles Motor Scale and 8 on early-hospital NIH Stroke Scale deficits.

In FAST-MAG, certain patients were more likely to be treated in the platinum half-hour:

• Acute cerebral ischemia: those with severe motor deficits on first prehospital assessment and younger age

• Intracranial cranial hemorrhage: women, non-Hispanic people, and people with more severe motor deficits

Jovin highlighted the paramedics' high rate of correct diagnosis of vascular emergency, as only 2.5% of FAST-MAG patients turned out to be stroke mimics.

The study authors acknowledged that they lacked routine early vessel imaging results after hospital arrival and follow-up imaging. This prevented them from assessing the impact of large vessel occlusion on early presentation, and also left them in the dark regarding post-arrival infarct growth and hematoma expansion.

"These data set the stage for future clinical trials to test the type of prehospital treatments that will be required to reach stroke patients during this crucial platinum time window," maintained Anthony Kim, MD, MAS, medical director of the University of California San Francisco Comprehensive Stroke Center.

He said that in the meantime, EMS agencies and emergency medicine departments are already using other strategies -- from improving public awareness of stroke symptoms to revamping prehospital triage and routing protocols -- to cut down time to treatment for stroke patients.

"The bottom line is one would expect better outcomes with earlier treatment," Grotta said.

• 

  Nicole Lou is a reporter for MedPage Today, where she covers cardiology news and other developments in medicine. Follow

Disclosures

FAST-MAG had been funded by an NIH grant.

Study co-authors disclosed relationships with Cerenovus, Medtronic, BrainsGate, BrainQ, Rapid Medical, Genentech, and Stryker.

Pariona-Vargas, Jovin, and Kim had no relevant disclosures.

Grotta reported consulting for companies that make mobile stroke units.

Primary Source

Stroke

Source Reference: Randhawa AS, et al "Beyond the golden hour: treating acute stroke in the platinum 30 minutes" Stroke 2022; DOI: 10.1161/STROKEAHA.121.036993.

 

Neuroprotectant delivered to brain in nanoparticles may improve stroke treatment, outcomes

Nothing will be done with this. No human testing. All because we have NO STROKE LEADERSHIP OR STRATEGY.  Also your stroke hospital doesn't know about this research and would do nothing to initiate research even if it did know about it.  When stroke size decreases by 70% using this just maybe all hands should be on deck to get this into human use. Just think of your children and grandchildren recovering much better than you if YOU start screaming at your stroke hospital to DO SOMETHING WITH THIS.

Your responsibility.

 

Neuroprotectant delivered to brain in nanoparticles may improve stroke treatment, outcomes

American Stroke Association International Stroke Conference - Presentation 65

American Heart Association

Research News

DALLAS, March 11, 2021 -- When NA1, a neuroprotectant, was delivered to the brain in nanoparticles, it reduced stroke severity and improved survival in a mouse model of stroke, according to preliminary research to be presented at the American Stroke Association's International Stroke Conference 2021. The virtual meeting is March 17-19, 2021 and is a world premier meeting for researchers and clinicians dedicated to the science of stroke and brain health.

In an earlier human trial (the ESCAPE-NA1 trial), NA1, a small peptide designed to save brain cells from death after stroke, showed mixed results when NA1 was administered to patients undergoing clot removal for severe stroke. Some patients in the trial also received the intravenous clot-busting medication tissue plasminogen activator (tPA), and these patients in particular showed a lack of improvement in functional outcomes from NA1.

"NA1 binds many organs, cells and proteins in the body. Without protection, it cannot get into the brain with high efficiency and specificity and may otherwise get into cells where we don't want it, or bind and deactivate other treatments, such as the clot-busting medicine tPA," said Jiangbing Zhou, Ph.D., co-senior author of the study and associate professor of neurosurgery and biomedical engineering at Yale University in New Haven, Connecticut.

To deliver NA1 precisely where it is needed, the research team in this study created stroke-targeting nanoparticles to encapsulate and deliver NA1 to portions of the brain being deprived of oxygen in a stroke mouse model.

In the mouse model study conducted from 2016 to 2020, researchers compared the ability of nanoparticles filled with NA1 and non-encapsulated NA1 to improve survival, reduce stroke size and reduce brain swelling. Both treatments contained the same dose of NA1 (50 micrograms) delivered intravenously to mice with blockage of a brain artery.

Researchers found:

• Stroke size was reduced 69.8% among mice treated with NA1-loaded nanoparticles, compared with 0.7% for those treated with NA1 that was not encapsulated.
• Brain swelling was reduced 60.3% among mice treated with NA1-loaded nanoparticles, compared with 3.3% for those treated with NA1 that was not encapsulated.
• Median days of survival were more than 14 days among mice treated with NA1-loaded nanoparticles (mice in this model usually survive significantly less than 14 days), compared to 6 days for those treated with NA1 that was not encapsulated.

"When delivered by nanoparticles, the same dose of NA1 that was not effective in an earlier study reached the stroke area and provided a surprising degree of effectiveness. The use of nanoparticles in stroke treatment may open new doors to delivering NA1 and other promising therapies to the brain," said Kevin N. Sheth, M.D., co-senior author of the study and professor of neurology and neurosurgery at Yale University.

Since the nanoparticles themselves act as antioxidants and may improve stroke outcome, some of the mice were also treated with nanoparticles not containing NA1. Those mice had intermediate improvements: stroke size reduced by 52.2%, brain swelling reduced by 30.2% and a median survival of 10 days.

"We have not had any recent major advances in the delivery of brain-protective agents for stroke. These results suggest a significant effort to change that landscape," Sheth said.

###

Additional co-authors are Shenqi Zhang, M.D., Ph.D.; Zeming Chen, Ph.D.; Gang Deng, M.D., Ph.D.; W. Taylor Kimberly, M.D., Ph.D.; and J. Marc Simard, M.D. Author disclosures are listed in the abstract.

The study was funded by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health and the American Heart Association.

Additional Resources:

Multimedia is available on the right column of release link https://newsroom.heart.org/news/neuroprotectant-delivered-to-brain-in-nanoparticles-may-improve-stroke-treatment-outcomes?preview=9b6b220108514c32edc3be315ac30bfe

 

Stroke-Targeting Nanoparticles Deliver Neuroprotectant to Mouse Brain

Nothing will be done with this. No human testing. All because we have NO STROKE LEADERSHIP OR STRATEGY.  Also your stroke hospital doesn't know about this research and would do nothing to initiate research even if it did know about it.  When stroke size decreases by 70% using this just maybe all hands should be on deck to get this into human use. Just think of your children and grandchildren recovering much better than you if YOU start screaming at your stroke hospital to DO SOMETHING WITH THIS.

Your responsibility.

Stroke-Targeting Nanoparticles Deliver Neuroprotectant to Mouse Brain

Written by AZoNanoMar 12 2021

According to a new study, the delivery of NA1, a neuroprotectant, to the brain in nanoparticles decreases stroke severity and enhances survival in a mouse model of stroke.

Image Credit: Alexandros A Lavdas/shutterstock.com

This is a preliminary study to be presented at the American Stroke Association’s International Stroke Conference 2021. The virtual meeting will be held from March 17^th to 19^th, 2021, and is a world premiere meeting for clinicians and researchers committed to the science of stroke and brain health.

In a previous human trial (the ESCAPE-NA1 trial), NA1, a small peptide that has been particularly developed to save brain cells from death following stroke, exhibited combined outcomes when NA1 was given to patients who were undergoing clot removal for severe stroke.

During the trial, a few patients were administered the intravenous clot-busting medication tissue plasminogen activator (tPA), and these patients specifically exhibited a lack of improvement in functional results from NA1.

NA1 binds many organs, cells and proteins in the body. Without protection, it cannot get into the brain with high efficiency and specificity and may otherwise get into cells where we don’t want it, or bind and deactivate other treatments, such as the clot-busting medicine tPA.

Jiangbing Zhou, PhD, Study Co-Senior Author and Associate Professor of Neurosurgery and Biomedical Engineering, Yale University

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In this study, to deliver NA1 accurately where it is required, the researchers made stroke-targeting nanoparticles to enclose and deliver NA1 to portions of the brain that are being deprived of oxygen in a stroke mouse model.

In the mouse model study performed from 2016 to 2020, the team matched the potential of nanoparticles loaded with NA1 and non-encapsulated NA1 to enhance survival and decrease brain swelling and stroke size. Both treatments included the same dose of NA1 (50 μg) administered intravenously to mice with a brain artery blockage.

The team discovered that:

• Stroke size decreased by 69.8% for mice treated with NA1-filled nanoparticles, compared to 0.7% for those treated with non-encapsulated NA1.
• Brain swelling decreased by 60.3% for mice treated with NA1-filled nanoparticles, compared to 3.3% for those treated with non-encapsulated NA1.
• Median days of survival were over 14 days for mice treated with NA1-filled nanoparticles (mice in this model generally live considerably less than 14 days), compared to 6 days for those treated with non-encapsulated NA1.

When delivered by nanoparticles, the same dose of NA1 that was not effective in an earlier study reached the stroke area and provided a surprising degree of effectiveness. The use of nanoparticles in stroke treatment may open new doors to delivering NA1 and other promising therapies to the brain.

Kevin N. Sheth, MD, Study Co-Senior Author and Professor of Neurology and Neurosurgery, Yale University

As the nanoparticles themselves have the tendency to serve as antioxidants and might enhance stroke outcome, few of the mice were also treated with nanoparticles without NA1. Those mice exhibited intermediate enhancements: stroke size decreased by 52.2%, brain swelling decreased by 30.2%, and the median survival was 10 days.

We have not had any recent major advances in the delivery of brain-protective agents for stroke. These results suggest a significant effort to change that landscape.

Kevin N. Sheth, MD, Study Co-Senior Author and Professor of Neurology and Neurosurgery, Yale University

The additional co-authors of the study are Shenqi Zhang, MD, PhD; Zeming Chen, PhD; Gang Deng, MD, PhD; W. Taylor Kimberly, MD, PhD; and J. Marc Simard, MD.

The research was financially supported by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health and the American Heart Association.

Source: https://www.heart.org/

 

The future of stroke patients may depend on the part-time job of a Canadian surgeon

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

By Oliver StaleyMarch 30, 2019

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.

NA-1 stroke drug a victory for basic research, says UPEI team

So I wonder which of the 5 causes of neuronal cascade of death this drug is addressing? Without that knowledge we really are just throwing darts in the dark.
http://www.cbc.ca/news/canada/prince-edward-island/na-1-stroke-drug-a-victory-for-basic-research-says-upei-team-1.3011749

A new stroke drug, which takes a new approach to treatment, shows the value of basic research, says a group of researchers at the University of Prince Edward Island.

The NA-1 drug treatment for stroke could change the landscape for the development of new drugs, says UPEI researcher Andy Tasker. (Maggie Brown/CBC)

The researchers did some of the research that led to the creation of the new drug. NA-1 will be tested by paramedics at five hospitals across the country as part of phase three clinical trials. Some members of the UPEI team also maintain part ownership of NoNO Inc., the company that is working to develop the drug and paying for the trials.
In previous trials, there was evidence the drug reduced cell death in stroke victims with minimal side-effects. NA-1 has so far shown to be beneficial for all types of stroke, not just ones caused by blood clots. Other medications are designed to break down clots in the brain, while NA-1 acts as a neuroprotectant, which enhances the brain's ability to withstand stroke.
Andy Tasker, one of the researchers who worked on the early stages of the drug at UPEI, said the latest trial is a watershed moment.
"If NA-1 proves effective in this trial it will change the landscape for the development of neuroprotectant drugs and is a wonderful endorsement of the value of investigator-driven, basic research in universities," said Tasker.
Tasker said this phase three trial is also a proud moment for the team at UPEI.
"To know that the part we played was critical in the development of this drug, to demonstrate that fundamental research really can lead to tangible benefits that benefit people in the real world in real time, and also frankly to show that a small university way out in the edges of the country can actually contribute to something which has the enormous potential to be a major impact worldwide," he said.
The trial began March 16 in Toronto and will then expand to other cities across Canada.

New drug trial puts possible stroke treatment in the hands of paramedics - in Canada - NA-1

The latest here:
http://www.healthcanal.com/brain-nerves/stroke/61247-new-drug-trial-puts-possible-stroke-treatment-in-the-hands-of-paramedics.html

The earlier trial of the drug here:

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

Only a year and a half between the two trials. I have no idea if that is fast or slow and since we have nobody in charge of the stroke strategy there is no one who can be asked.  We have absolutely NO leaders in stroke. Nature abhors a vacuum.

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

Is this enough to push out to all stroke hospitals?
Who is going to do that? I want a name.
http://www.thelancet.com/journals/laneur/article/PIIS1474-4422%2812%2970225-9/abstract

Background

Neuroprotection with NA-1 (Tat-NR2B9c), an inhibitor of postsynaptic density-95 protein, has been shown in a primate model of stroke. We assessed whether NA-1 could reduce ischaemic brain damage in human beings.

Methods

For this double-blind, randomised, controlled study, we enrolled patients aged 18 years or older who had a ruptured or unruptured intracranial aneurysm amenable to endovascular repair from 14 hospitals in Canada and the USA. We used a computer-generated randomisation sequence to allocate patients to receive an intravenous infusion of either NA-1 or saline control at the end of their endovascular procedure (1:1; stratified by site, age, and aneurysm status). Both patients and investigators were masked to treatment allocation. The primary outcome was safety and primary clinical outcomes were the number and volume of new ischaemic strokes defined by MRI at 12—95 h after infusion. We used a modified intention-to-treat (mITT) analysis. This trial is registered with ClinicalTrials.gov, number NCT00728182.

Findings

Between Sept 16, 2008, and March 30, 2011, we randomly allocated 197 patients to treatment—12 individuals did not receive treatment because they were found to be ineligible after randomisation, so the mITT population consisted of 185 individuals, 92 in the NA-1 group and 93 in the placebo group. Two minor adverse events were adjudged to be associated with NA-1; no serious adverse events were attributable to NA-1. We recorded no difference between groups in the volume of lesions by either diffusion-weighted MRI (adjusted p value=0·120) or fluid-attenuated inversion recovery MRI (adjusted p value=0·236). Patients in the NA-1 group sustained fewer ischaemic infarcts than did patients in the placebo group, as gauged by diffusion-weighted MRI (adjusted incidence rate ratio 0·53, 95% CI 0·38—0·74) and fluid-attenuated inversion recovery MRI (0·59, 0·42—0·83).

Interpretation

Our findings suggest that neuroprotection in human ischaemic stroke is possible and that it should be investigated in larger trials.