Project 464091

Amyotrophic lateral sclerosis (ALS) is a neurologic disease in which patients gradually lose the use of their muscles. This causes problems with mobility, self-care, speech, swallowing and breathing. The disease worsens quickly and usually leads to death within three years of diagnosis. The diagnosis is made using clinical examination and by ruling out other diagnoses. Unfortunately, there is no treatment to alleviate symptoms and extend survival and there is even no biomarker to confirm the presence of the disease and assess disease progression. For unknown reasons, ALS affects males more than females; the age of disease onset is also earlier for males than females with ALS. Interestingly, changes in the bacterial composition in the gut are found in ALS patients. These gut bacteria are also inherently different between the males and females, suggesting that they may represent an important factor to explain the susceptibility for males in disease. In addition, the gut bacterial composition is influenced by the environment and diet, requiring monitoring of these variables. In this grant, we propose to identify the bacteria that are associated with the preferential vulnerability of males for ALS and protection in females. To do this, we have brought together a team of researchers from Canada, Israel and Turkey to recruit ALS and non-ALS subjects that we will follow throughout disease. The participants will provide us with saliva and stool samples for bacterial analysis. In parallel, we will collect blood samples to measure metabolic changes and correlate them with the gut and oral bacterial changes. We will then test the bacteria-derived metabolites in animals in our laboratory to confirm that they are important to the development and progression of disease. We hope to identify biomarkers and molecules that explain the higher risk to males for development of ALS and confer protection to females, and to develop future treatments for this devastating disorder.