THERAPEUTIC STRATEGIES USING SULINDAC AND G-CSF GENE THERAPY FOR NEUROLOGICAL DISEASE

Alzheimer’s disease is a neurodegenerative disease that causes cognitive dysfunction and leads to progressive memory loss and behavioral impairment. About 60% to 80% of dementia cases are attributed to Alzheimer’s disease and currently afflict about 50 million people worldwide. Although it primarily affects people over the age of 65, a person’s risk for developing Alzheimer’s disease earlier can depend on factors such as a family history (genetic inheritance) or experiencing an ischemic stroke event. Current treatments for Alzheimer’s disease include behavioral therapy and drug treatment that can lessen the severity of symptoms but cannot stop progression indefinitely. Sulindac is a non-steroidal anti-inflammatory drug that, by a mechanism independent of its anti-inflammatory properties, has shown to express a preconditioning response to protect from oxidative damage. Granulocyte colony stimulating factor is a hematopoietic glycoprotein that can stimulate the production of granulocytes and stem cells that has proven to provide neuroprotection in models of ischemic stroke via mechanisms including anti-apoptosis and anti-inflammation. In this in vitro study, the potential neuroprotective effects of Sulindac is measured against the effects of oxidative stress when subjected to hypoxia and reperfusion. Regarding un-transfected SHSY-5Y cells, hypoxia was demonstrated to lower cell viability starting at a period of 12 hours. It was found that a low concentration of Sulindac (200 uM) was effective in protecting SHSY-5Y cells against oxidative stress and overall lowering the rate of cell death in the event of hypoxic and reperfusion injury. When SHSY-5Y cells were transfected with Swedish APP mutation, cell viability was also markedly decreased in hypoxic conditions. However when treated with a concentration of 600 uM of Sulindac, cell viability levels were near matched with its normoxic counterparts