Gut microbiome could unlock new Parkinson’s diagnostics, treatments

Micrograph of Clostridium perfringens, one of the bacteria commonly found in the human gut. Image: CDC

Caltech researchers have shown in mouse models that gut bacteria can encourage the progression of some Parkinson’s disease hallmarks. These bacteria could serve as biomarkers or therapeutic targets for the neurodegenerative disease.

Previous research has shown that communication between the gut and brain plays a role in neurological disorders, such as anxiety and depression. This study, led by Caltech microbiology professor Sarkis Mazmanian and published in the journal Cell, is the first to suggest that changes in the gut microbiome have a bearing on the onset and severity of Parkinson’s disease.

Mazmanian cofounded the new Axial Biotherapeutics, which has licensed worldwide rights to a class of biotherapeutics aimed at treating patients with central nervous system disorders. The company picked up $19.15 million in Series A financing and announced its launch on Tuesday. Longwood Fund and Domain Associates led the financing, with participation from Kairos Ventures and Heritage Medical Systems.

For the Parkinson's study, the Mazmanian's team used mouse models that over-express the protein alpha-synuclein, which is believed to be important in the progression of Parkinson’s disease. To examine how changes in the gut microbiome affected these Parkinson’s-predisposed mice, they transplanted gut bacteria from Parkinson’s patients and healthy humans into the mice.

“When we transplanted the microbiome from Parkinson’s patients into mice, we found that symptoms like motor deficits and neuroinflammation were more severe compared to mice harboring gut bacteria from healthy controls,” Mazmanian said in the statement. “This suggests there is a fundamental relationship between bacteria in the gut and the disease processes involved in Parkinson’s.”

Parkinson’s patients typically take drugs to control physical symptoms, which worsen over time. The blood-brain barrier, which stops almost all small and large molecules from entering the brain, has been an obstacle to the development for neurotherapeutic drugs.

Mazmanian will now focus on identifying the specific bacteria that may have a hand in driving Parkinson’s development, he said. “Gut bacteria provide immense physiological benefit, and we do not yet have the data to know which particular species are problematic or beneficial in Parkinson’s disease,” he said. Future findings, he added, "could lead to novel therapeutic approaches that avoid the complications of delivering drugs to the brain and may be safer and more effective.”