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Axial finds link between gut microbiome and Parkinsonís disease
12-13-2016
by Jeffrey Bouley  |  Email the author
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BOSTON & PASADENA, Calif.—Axial Biotherapeutics announced Dec. 1 that researchers from the California Institute of Technology (Caltech), led by Dr. Sarkis K. Mazmanian, the company’s scientific founder, have discovered a novel biological link between the gut microbiome and Parkinson’s disease (PD).
 
In a validated PD mouse model, gut bacteria were shown to promote hallmark disease processes including inflammation of the nervous system and motor dysfunction. The findings suggest that targeting the gut microbiome may provide a new approach for diagnosing and treating Parkinson’s disease. The paper titled, “Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson’s Disease,” can be accessed in the current online edition of Cell.
 
Over the past few years, evidence has accumulated pointing to a critical role of the gut microbiome in human health and disease, according to Axial, adding that bidirectional communication between the gut and the brain has been implicated in neurological disorders such as anxiety, depression and autism spectrum disorders. The recent research conducted with Caltech, published recently in Cell, is reportedly the first to find that alterations to bacteria in the gut may represent a risk factor for the onset and severity of Parkinson’s disease.
 
This finding opens the door for the potential identification of specific gut microbes that may impact PD, Mazmanian says, and in the future, these microbes might be used as a biomarker for disease states, both as a method to identify patients who might be at risk for PD and as a novel therapeutic targets or microbial-based treatments.
 
“Our findings provide a completely new paradigm for how environmental factors may contribute to Parkinson’s disease and possibly other neurodegenerative disorders. The notion that these diseases may be impacted by pathology in the gut and not only in the brain is a radical departure from conventional research in neuroscience,” said Sarkis Mazmanian, who is also the Louis & Nelly Soux Professor of Microbiology in the Division of Biology and Biological Engineering at Caltech. “Parkinson’s disease is complex and there are several genetic predispositions and environmental risks that play a role, but we believe our findings shed light on a previously unrecognized and potentially important part of this puzzle.”
 
“Gut bacteria in patients with Parkinson’s disease are different from those microbes found in healthy individuals,” Mazmanian continued. “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. This suggests that there is a fundamental relationship between bacteria in the gut and the disease processes involved in Parkinson’s disease.”
 
To conduct their experiments, the researchers utilized a mouse model of Parkinson’s disease that overexpresses the human protein alpha-synuclein. This protein is thought to be central to the disease process of PD. The mice were bred in a germ-free setting, devoid of all microbes. Using the germ-free animals as a platform, the researchers could then investigate how gut bacteria altered disease outcomes in mice. When human gut microbiota from PD patients were introduced into the model system (by fecal microbiota transplants), they were shown to enhance the typical hallmarks of the disease such as motor deficits, inflammation and alpha-synuclein aggregation, compared to microbiota transplants from healthy human donors.
 
The researchers also identified specific microbial metabolites that induce PD-related symptoms in mice. These findings suggest that gut microbes may contribute to, or even cause, PD symptoms in genetically predisposed individuals. The studies were carried out by a multidisciplinary team from Caltech; the University of California, San Diego; Arizona State University; Chalmers University of Technology in Gothenburg, Sweden; the University of California, Los Angeles; Rush University Medical Center in Chicago and the University of Wisconsin—Madison.
 
“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,” noted Mazmanian. “It is important to note that there are currently no antibiotic or microbial treatments available for human use that can replicate the effect we observed in mice. However, our next step will be to define the specific gut microbes that may contribute to the development of Parkinson’s disease, as this could translate into novel biomarkers to identify at-risk patients. Additionally, these findings could lead to novel therapeutic approaches that avoid the complications of delivering drugs to the brain and may be safer and more effective.”
 
“Axial Biotherapeutics will build on these groundbreaking findings and the larger body of work that our scientific founder, Dr. Sarkis Mazmanian, has established in this area. Our goal as a company will be to focus on translating these discoveries into a unique class of microbial-targeted therapeutics that could become breakthrough therapies for a variety of underserved neurological diseases and disorders, including autism spectrum disorder, Parkinson’s and Alzheimer’s disease,” said Dr. David Donabedian, CEO of Axial Biotherapeutics.
 
Axial has executed a license agreement that provides worldwide exclusivity to related intellectual property from Caltech in applications for neurological diseases and disorders.
 
It was only at the end of November that Axial launched, announcing a $19.15-million Series A round of financing as part of its introduction to the central nervous system (CNS) and gut microbiome spaces. The company seeks to leverage what it calls the “groundbreaking work” of Mazmanian, which uses the gut microbiome to help treat CNS-related diseases and disorders.
 
“By interrogating the biological link between the gut microbiome and the brain, we are discovering pathways and mechanisms that can be leveraged to develop novel treatment options for vastly underserved diseases,” said Mazmanian. “The discovery that changes in the gut microbiome may cause neurological diseases is a paradigm shift and opens entirely new possibilities for treating patients.”
 
The Mazmanian Laboratory was among the first to demonstrate disease modifying effects in mouse models of autism spectrum disorders via novel and proprietary microbiome interventions. Axial plans to leverage those findings to build a microbiome discovery platform targeting the gut-brain axis which provides the opportunity to generate a diverse pipeline of new therapies for patients with neurological diseases and disorders.
 
The Series A financing was led by Longwood Fund and Domain Associates. Also participating in the financing were Kairos Ventures, Heritage Medical Systems and a group of high-net-worth individuals based in Southern California.
 
Code: E12141602

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