Fasudil, cerebral blood flow and Michael J. Fox
July 31, 2011 at 1:36pm
In the news today, Michael J. Fox's foundation for Parkinson's research has awarded a grant to study a relatively new drug that improves cerebral blood flow after ischemic injury. What is interesting is that this drug is also being studied as a treatment for MS. This is the kind of drug that makes sense; one that helps after axonal death due to ischemia. Let's also hope that CCSVI and the International Society for Neurovascular Disease research provides more answers for those with Parkinson's.
____________________________________________________________________
GRAND RAPIDS -- Actor Michael J. Fox's foundation for Parkinson's research has awarded a $400,000 grant to fund research by Grand Rapids scientists into a drug that has the potential to halt the progression of the disease.
The focus of their efforts is Fasudil, a drug already approved in Japan to improve blood flow to the brain in stroke victims. It has shown similar positive outcomes in the U.S. in late-stage clinical trials.
Fasudil also showed potential for improving learning and memory and reducing the risk of Alzheimer's in a 2009 study by TGen and Arizona State University. VARI investigators discovered its potential for treating Parkinson's while testing drugs to reduce the toxicity caused by a gene implicated in Parkinson's disease.
"Fasudil has a very favorable safety profile in humans and is already available in Japan as an oral tablet, so upon successful milestone completion, we could be seeing clinical trials within two to three years," MacKeigan said in a statement.
http://news.msu.edu/story/9622/
______________________________________
The reason it is also news for those of us in CCSVI, is because of Fasudil's affect on the endothelium, cerebral blood flow and nitric oxide. This compound could be very helpful in recovery from brain and spinal cord injury due to CCSVI. Here are some more studies on this drug:
Fasudil protects hippocampal neurons against hypoxia-reoxygenation injury by suppressing microglial inflammatory responses in mice.
Rho kinase (ROCK) may play an important role in regulating biological events of cells, including proliferation, differentiation and survival/death. Blockade of ROCK promotes axonal regeneration and neuron survival in vivo and in vitro, thereby exhibiting potential clinical applications in spinal cord damage and stroke. Our previous studies have demonstrated that Fasudil, a selective ROCK inhibitor, induced neuroprotection in vitro. Here we used an in vivo model of hypoxia/reoxygenation (H/R) injury to examine the neuroprotective effect of Fasudil, and explore its possible mechanism(s) in vivo. H/R resulted in the loss of hippocampal neurons, accompanied by increased apoptosis of neurons in hippocampus. The expression of ROCK II and activity of ROCK in the brain were increased after H/R, and located only in microglia, but not in astrocytes and neurons. The administration of Fasudil inhibited the activity of ROCK in brain tissue and cultured microglia, and protected hippocampal neurons against H/R injury. Further immunohistochemical analysis and cytokine determination revealed that Fasudil inhibited inducible nitric oxide synthase immunoreactivity in microglia and pro-inflammatory factors in brain tissue after H/R, which is consistent with the observation wherein Fasudil reduced the pro-inflammatory factors nitric oxide, IL-1β, IL-6 and TNF-, and increased anti-inflammatory factor IL-10 in cultured microglia under normoxic or hypoxic conditions. Our results indicate that inhibition of ROCK by Fasudil may represent a useful therapeutic perspective by inhibiting microglial inflammatory responses in the CNS
http://www.ncbi.nlm.nih.gov/pubmed/20882700
Rho kinase inhibitor Fasudil induces neuroprotection and neurogenesis partially through astrocyte-derived G-CSF
Abstract
Rho-kinases (ROCK) are serine/threonine kinases that play an important role in fundamental processes of cell migration, proliferation and survival. Blockade of ROCK promotes axonal regeneration and neuroprotection, thereby exhibiting therapeutic potentials for clinical application to spinal cord damage and stroke. Here we explored the mechanisms of Fasudil, a ROCK inhibitor, in neuroprotection and neurogenesis by using oxygen–glucose deprivation (OGD) as an in vitro ischemia model. Fasudil stimulates astrocytes to produce granulocyte colony-stimulating factor (G-CSF). Astrocyte-conditioned medium treated with Fasudil (ACM-F) contributes to the generation of neurospheres, and decreases neuron death. Neutralization of G-CSF in ACM-F and blocking of G-CSF receptor in neuronal cell cultures revealed that Fasudil-induced neuroprotection and/or neurogenesis are mediated partially through astrocyte-derived G-CSF. Our results indicate that ROCK inhibition by Fasudil, protecting neurons and mobilizating neural stem cells, might represent a useful therapeutic perspective for various neurological disorders characterized by neuron death.
No comments:
Post a Comment