The leuktotriene signaling pathway in Lewy Body Dementias

Lewy body dementia is, after Alzheimers disease, with approximately 15 Mio affected patients worldwide the second most frequent form of dementia. Lewy body dementia can affect anyone, we do not know the origin of the disease, age is the main risk factor. The currently available treatments are to ease temporarily the symptoms, they do neither stop disease progression no do they cure the disease. We have identified a mechanism in the brain that is very likely to contribute to the cognitive deficits in patients with Lewy body dementia. We could already show that treatment of mice with a Lewy body dementia type of cognitive impairment with a drug blocking this proposed mechanism restored learning and memory in these animals. Also, the drug was able to act on some central points of the underlying pathology such as on brain inflammation and on certain protein aggregates that accumulate in Lewy body dementia. We now want to identify the underlying mechanisms of Lewy body dementia and specify more in detail the mode of action of our therapeutic intervention. This project will create a better understanding of Lewy body dementia and will be an essential step in the development of a therapy for patients with this disease.

Lewy Body Dementia is related to Parkinson's disease. Both are age-related neurodegenerative diseases without any current curative therapies. Therefore, there is a huge unmet need to develop effective therapies. We have identified a novel mechanisms (leukotriene signaling) that contributes to the disease and have explored the possibility to block the action of leukotrienes with the use of the already existing drug Montelukast with the hypothesis to reduce pathology and to improve function. Indeed, in experiments on animals with Lewy Body Dementia and with Parkinson's disease, we could show that this drug lowers neuroninflammation in the brain and imrpoves cognitive (Lewy Body Dementia) and motor (Parkinson's disease) functions. Besides this, we develoloped a new and improved packaging of the drug, which has now been tested in patients with Alzheimer's disease with positive preliminary results and with Parkinson's disease (clinical trial has recently been started). This project might indeed be the groundwork for a novel drug to effectively treat patients with neurodegenerative diseases. In case of support and interest from big pharmaceutical industry, this drug might enter the market within the next years.