Pro-inflammatory cytokine production can be beneficial to the human body, as it is part of the body’s biological response. However, overproduction of these proteins promotes the development of many deteriorating neurological diseases, such as Alzheimer’s disease (AD) and the neurological damages that are aftereffects of traumatic brain injury (TBI) and stroke. High levels of pro-inflammatory cytokines inhibit proper synaptic communication and function, which eventually leads to damages in the cortex and hippocampus of the brain.

In a study from Northwestern’s Feinberg School of Medicine and University of Kentucky, a new set of drugs have been developed that targets this issue by preventing the overproduction. These drugs target neuroinflammation, a type of brain inflammation that is believed to be a major factor in the injurious nature of diseases ranging from Alzheimer’s to Parkinson’s, as well as brain injuries. The drugs, currently represented by MW151 and MW189, have been tested in previous animal studies. MWI151 was given to a six-month old (the time at which the level of pro-inflammatory cytokines being to increase) mice that are genetically engineered to develop AD for three times a week; then, their brains were examined at eleven months of age, the time at which the conditions of AD are visible. The development of the full-blown AD was avoided as the level of cytokines had returned to normal levels and their synapses were working properly. Mice that were not given the drug still had high levels of pro-inflammatory cytokines and had synaptic malfunction.  In another cases, it has also helped decrease the nerve damage caused by TBI by preventing overproduction of pro-inflammatory cytokines and blocking the activation of glia cells. Success was also met when the drug was tested in mice to prevent the development of multiple sclerosis.

Phase one of the first human clinical trial has been completed, but these current studies have shown that the therapy time window is limited, so for future clinical trials, further studies involving models of other diseases and time windows will be conducted. With this new development, the future of early therapy to prevent the development of neurological diseases and the long-term complications of TBI and strokes seems promising.

Keywords: inflammation; pro-inflammatory cytokines; drug; Alzheimer’s disease; traumatic brain injury



      (Early Stage Drug Treatment That Normalizes Proinflammatory Cytokine Production Attenuates Synaptic Dysfunction in a Mouse Model That Exhibits Age-Dependent Progression of Alzheimer’s Disease-Related Pathology)

Wendy Liu

July 25, 2012