Stroke, a cardiovascular event, occurs when the brain's supply of blood is obstructed, meaning that an area of the brain does not receive enough oxygen.
The most common type of stroke is ischemic stroke, which is caused by a blood clot obstructing a blood vessel.
In the United States, more than 795,000 people have a stroke per year, according to the Centers of Disease Control and Prevention (CDC). Stroke is also responsible for 1 in 20 deaths every year.
Treatment for acute ischemic stroke is done by administering tissue plasminogen activator (tPA), which is the only drug approved by the Food and Drug Administration (FDA) for the treatment of stroke. This drug type acts by dissolving obstructive blood clots, in order to allow blood to flow normally again.
However, tPA has a number of shortcomings, including the fact that it has to be administered within a fairly short window of time — 4.5 hours from the event — and that it is sometimes accompanied by serious complications, such as intracranial hemorrhage.
The road to a reliable treatment
In an effort to find an additional treatment that may protect against some of these effects, scientists from The Scripps Research Institute (TSRI) in La Jolla, CA, have developed a new drug called 3K3A-APC.
The drug is an engineered variant of activated protein C, which humans normally produce. It has been linked to the regulation of blood clotting and to certain aspects of the body's inflammatory response.
A preliminary phase II clinical trial of 3K3A-APC has so far suggested that the drug is safe to use in humans.
"These results lay the groundwork for the next steps toward FDA approval," says John Griffin, who was one of the researchers involved in the development of the experimental drug.
Preclinical studies testing the efficacy and safety of the newly developed drug were conducted by Griffin's laboratory at TSPI, in collaboration with that of Dr. Berislav Zlokovic, from the Zilkha Neurogenetic Institute at the University of Southern California in Los Angeles, CA.
Initial tests suggest that the experimental drug not only decreased any damage consistent with stroke, but it also shielded the brain from the complications normally caused by tPA.
Experimental drug has protective effects
This new clinical trial was placebo-controlled, meaning that the drug's actual efficacy was tested against a placebo. It also set out to confirm how high a dose of the experimental drug would be safe for human participants.
Therefore, the scientists recruited 110 people who had had acute ischemic stroke and who were following treatment with tPA, intra-arterial thrombectomy, or both of these therapies.
The participants — all aged between 18 and 90 — were followed for a period of 90 days, as they were administered varying doses of the experimental drug.
The scientists experimented with four different dosages — 120, 240, 360, and 540 micrograms per kilogram. All four dose levels — including the highest one — were tolerated well by the subjects, so the researchers declared them safe for human use.
Also, the drug was seen to perform well in terms of results related to intracranial hemorrhage, or brain hemorrhage.
It was found that the drug helped to reduce both total hemorrhage volume, or how much blood "leaked," and hemorrhage incidence, or how often the participants experienced this event, significantly.
"The observed trend toward lower hemorrhage rates is consistent with our expectations based on the drug's mechanism of action and activity in animal studies," says Dr. Patrick Lyden, one of the researchers involved with the current clinical trial.
But he adds that "[t]hese results should be confirmed in a larger clinical trial." This, the researchers explain, will be their next step. They aim to eventually get FDA approval for the experimental drug.