An experimental anti-inflammatory drug has positive effects on neuron function and amyloid plaques in a mouse model of Alzheimer’s disease, Emory neuroscientists report. The findings are published in the journal Neurobiology of Disease.
Inflammation’s presence in Alzheimer’s is well established, but it is usually thought of as an accelerator, rather than an initiating cause. While everybody argues about the amyloid hypothesis, there’s a case to be made for intervening against the inflammation. Exactly how is an open question.
The drug tested, called XPro1595, targets the inflammatory signaling molecule tumor necrosis factor (TNF). Commercialized drugs such as etanercept and infliximab, used to treat autoimmune diseases, also block TNF. However, XPro1595 only interferes with the soluble form of TNF and is supposed to have less of an effect on overall immune function.
Senior author Malu Tansey (pictured) and her colleagues say that interfering with TNF could have direct effects on neurons, as well as indirect effects on the immune cells infiltrating the brain. They write that “the most promising finding in our study” is the ability of XPro1595 to restore long-term potentiation or LTP, which is impaired in the Alzheimer’s model mice. LTP refers to strengthening of connections between neurons when they are stimulated, and is thought to be a mechanism underlying learning and memory. Researchers from McGill University recently obtained similar results using XPro1595 and a different mouse model of Alzheimer’s.
The first author of the Neurobiology of Disease paper is Neuroscience graduate student Kathryn MacPherson. Tansey says her lab is now examining interactions with high-fat/fructose diet and hypertension in the Alzheimer’s model. She and her colleagues previously showed that XPro1595 can also prevent neuron loss in a rat model of Parkinson’s.
Caution is in order when translating findings from Alzheimer’s mouse models to the clinic. Several interventions were initially shown to be beneficial in Alzheimer’s mice — examples include the skin cancer drug bexarotene (hasn’t been confirmed clinically) and flickering lights (newer and thus not tested yet).