Project Overview

Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease in humans. The disease is caused by the degeneration of motor neurons that innervate the voluntary muscles, leading to respiratory failure and death within about 3 years from onset. A central feature of ALS is the abnormal accumulation of misfolded proteins within and outside the central nervous system. This protein overload has been shown to promote neurodegeneration and strategies aiming at removing the accumulating proteins hold great promises for the treatment of ALS.

Our recent work indicates that the composition of the gut microbiota (i.e., the vast ensemble of bacteria that populate the gut) is important for the pathogenesis of mouse models of ALS, with some bacteria being protective and other detrimental to the disease. We also found that these mice display marked alterations in both the structure and function of the glymphatic system. The glymphatic is a brain-specific lymphatic system that serves as a channel for immune cell migration, drains fluids and removes toxic proteins and waste from the parenchyma. On the basis of these exciting results, we hypothesize that the composition of bacteria in the gut determines the structure, function and content of the glymphatic system.

As the microbiome and glymphatic system are modifiable through lifestyle (i.e. diet and sleep, respectively), our project may offer the unique opportunity to elaborate non-invasive therapeutic strategies. Ultimately, we aim to develop novel therapies centered on the gut microbiota to improve glymphatics, thereby removing toxic proteins from the brain and slowing down neurodegeneration in ALS.

Principal Investigator

Eran Elinav , Weizmann Institute of Science