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Engineering the Gut Microbiota to Treat Hyperammonemia

Description:

 

Introduction of microbial compositions with minimal activity of ammonia production can alter the microbial community in the gut and reduce overall ammonia production.

 

Technology

 

Increasing evidence indicates (i) that the gut microbiota can be altered to ameliorate or prevent disease states, and (ii) that engineering the gut microbiota to therapeutically modulate host metabolism is an emerging goal of microbiome research.

 

In the intestine, bacterial urease converts host-derived urea to ammonia and carbon dioxide, contributing to hyperammonemia-associated neurotoxicity and encephalopathy in patients with liver disease.

 

Dr. Wu et al engineered gut microbiota to reduce urease activity.

 

POC:

 

Animals were depleted of their preexisting gut microbiota and then inoculated with Altered Schaedler Flora (ASF), a defined consortium of 8 bacteria with minimal urease gene content. This resulted in establishment of a persistent new community that promoted a long-term reduction in fecal urease activity and ammonia production.

 

In a murine model of hepatic injury, ASF transplantation was associated with decreased morbidity and mortality demonstrating that inoculation of a prepared host with a defined gut microbiota can lead to durable metabolic changes with therapeutic utility.

 

Application

 

Potential treatment of gut dysbiosis in liver diseases, congenital hyperammonemia or Crohn’s disease.

 

Applications

 

•       Therapy for metabolic diseases that lead to hyperammonemia.

  

Advantages

 

•       Altered microbial composition in gut and reduced level of ammonia in vivo.

•       Unlike treatment with antibiotics, no development of antibiotic resistance

 

Stage of Development

 

Preclinical Discovery

 

Intellectual Property

 

1.       Issued Patent(s): 10,058,576

2.       Application Pending in the US, EU, AU, CA

 

 

Reference Media

 

Ni et al. Sci Transl Med, 2017, 9 – 416.

Shen et al. PLoS One, 2016, 11 – 5.

Shen et al. J Clin Invest, 2015, 125 – 2841.

 

Desired Partnerships

 

1.       License

2.       Co-development

 

Docket #: 14-6818

 

 

Download pdf


Patent Information:
For Information, Contact:
Viviane Martin
Director, PSOM Licensing Group
University of Pennsylvania
215-746-4275
martinv@upenn.edu
Inventors:
Gary Wu
Frederic Bushman
James Lewis
Keywords: