Friday, March 02, 2012

New Experimental Drug Offers Hope for Early Stroke Treatment

Number of deaths for leading causes of death
Heart disease: 599,413
Cancer: 567,628
Chronic lower respiratory diseases: 137,353
Stroke (cerebrovascular diseases): 128,842
Accidents (unintentional injuries): 118,021
Alzheimer's disease: 79,003
Diabetes: 68,705
Influenza and Pneumonia: 53,692
Nephritis, nephrotic syndrome, and nephrosis: 48,935
Intentional self-harm (suicide): 36,909 _CDC US Leading Causes of Death
As shown above, stroke -- cerebrovascular accident (CVA) -- is the 4th ranking cause of death in the US. Besides mortality, there is also significant morbidity and disability associated with stroke worldwide.

Recent research at Toronto Western Hospital provides reason to hope for better drug treatments for stroke in the near future. The researchers tested a new type of drug -- a PSD-95 inhibitor -- in primates, in an acute stroke setting. Some of their results are pictured below.

A phase 2 clinical trial in humans was also recently completed in Ontario.

Nature

In a series of experiments, Michael Tymianski and colleagues at Toronto Western Hospital in Ontario, Canada, replicated the effects of stroke in macaques before intravenously administering a PSD-95 inhibitor, or a placebo. PSD-95 inhibitors interfere with the process that triggers cell death when the brain is deprived of oxygen.

To test its effectiveness the team used MRI to measure the volume of damaged brain for 30 days following the treatment, and conducted behavioural tests at various intervals within this time.

Monkeys treated with the PSD-95 inhibitor one hour after stroke had 55 per cent less damaged tissue in the brain after 24 hours and 70 per cent less after 30 days, compared with those that took a placebo. These animals also did better in behavioural tests. Importantly, the drug was also effective three hours after stroke.

...An early stage clinical trial in humans, run by firm NoNO in Ontario has also seen positive results. _NewScientist
Nature study abstract

PSD-95 Overview

PSD-95 complex as drug target for antidepressant development

The Role of PSD-95 and Cypin in Morphological Changes in Dendrites Following Sublethal NMDA Exposure Interesting abstract providing information on underlying factors involved.

This is a line of treatment which has been obvious for decades, but which has lacked the proper basic science backing up until now. Although PSD-95 inhibitors will not prevent all brain damage from occurring in stroke, nor will they restore damaged brain to normal function afterward, they do seem to limit the amount of damage that occurs, for each stroke.

It is a type of stop-gap measure, meant to prolong relative normal function as long as possible. More optimal developments for the future will involve better preventive measures and ways to rejuvenate damaged brain after the insult occurs. Full spectrum medical care will eventually involve all avenues of treatment, prevention, and restoration.

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