In hopes of finding effective treatments and possibly even a cure for dementia, scientists have been searching for ways to reverse memory deficits and impairments. For many years, advances in this area was challenging due to little knowledge about the cellular pathways which underlie dementia. However, promising research emerged in June 2018 when researchers at the Lewis Katz School of Medicine at Temple University were able to reverse cognitive impairments in mice with dementia.
The study, published in the journal Molecular Neurobiology, showed for the first time in an animal model, that a drug can reverse tau pathology – the second-most important brain lesion in dementia patients. As senior investigator Dr. Domenico Praticò explains, “We show that we can intervene after disease is established and pharmacologically rescue mice that have tau-induced memory deficits.”
The researchers discovered that dementia is related to damage to nerve cells from inflammatory molecules known as leukotrienes. The team then aimed to test if blocking leukotrienes could reverse the cognitive impairment in mice with dementia. This was done by injecting the mice with zileuton – a drug that inhibits the formation of leukotriene by blocking the 5-lipoxygenase enzyme.
At the end of the 16-week treatment period, the mice were put into maze tests to assess their working and spatial learning memory. In comparison to the untreated animals, the tau mice that were injected with zileuton performed significantly better, suggesting that zileuton successfully reversed the cognitive impairment.
In fact, the researchers found a 90% reduction in leukotrienes in the treated mice compared to the untreated group. As well, levels of phosphorylated and insoluble tau decreased by 50% in treated animals. Insoluble tau is known to directly damage synapses; thus, microscopic examination revealed severe synaptic deterioration in the untreated animals, while the synapses of the treated mice appeared to be undamaged. As said by Dr. Praticò, “Inflammation was completely gone from tau mice treated with the drug. The therapy shut down inflammatory processes in the brain, allowing the tau damage to be reversed.”
More information on the study conducted by the team at the Lewis Katz School of Medicine at Temple University can be found here: https://www.sciencedaily.com/releases/2018/06/180608101905.htm
