Metabolic Compound Reduces Stroke Damage

A new study reports that a drug under development for the treatment of metabolic disease disorders, including obesity, has been found effective in reducing stroke damage, even when administered post-stroke.

Researchers at the University of Connecticut Health Center (USA) evaluating the safety of 5' adenosine monophosphate-dependent protein kinase (AMPK)--a fatty acid synthase inhibitor--discovered that not only was the compound non-toxic in the brain, but that it also provided significant neuroprotection in the case of ischemic stroke. The researchers induced focal stroke by reversible middle cerebral artery occlusion in male wild-type mice, as well as mice deficient in one of the isoforms of the catalytic subunit of AMPK, AMPK alpha-1 or alpha-2. They found that mice deficient in AMPK alpha-2 demonstrated significantly smaller infarct volumes compared with wild-type littermates, whereas deletion of AMPK alpha-1 had no effect.

"AMPK activation is detrimental in a model of focal stroke,” concluded lead author assistant professor Louise McCullough, M.D., Ph.D., and colleagues of the department of Neurology. "The AMPK catalytic isoform alpha-2 contributes to the deleterious effects of AMPK activation. AMPK inhibition leads to neuroprotection even when these agents are administered post-stroke.”

The compound, labeled C75, is intended for the treatment of metabolic disease disorders, and regulates appetite by fatty acid synthase inhibition (FASi) in the hypothalamus. The compound is under development by FASgen (Baltimore, MD, USA). FASgen has also designed and synthesized other compounds that selectively inhibit fatty acid biosynthesis. One group of these compounds is intended for new highly specific therapeutics for cancer; additional compounds have the potential of specific therapeutics for obesity and related metabolic disorders; and an additional group of compounds have the potential of specific therapeutics for tuberculosis (TB), including multiple drug resistant TB (MDR-TB) and latent TB infections that affect one third of the world's population.


Related Links:
University of Connecticut Health Center
FASgen