Pioneering Study Describes Rationally Designed Drug Candidate Derived From the Human Microbiota

[Igor_Passau]

BOSTON, July 10, 2013 /PRNewswire/ -- Scientists have described one of the first instances of a rationally designed drug candidate derived from the human microbiota. The work was led by Dr. Kenya Honda, Team Leader of the Laboratory for Intestinal Homeostasis at the RIKEN Center for Integrative Medical Sciences (IMS) and scientific co-founder of Vedanta Biosciences. The paper describing the findings was published in today's issue of the journal Nature, and technology originating from the work has been licensed and is being advanced by Vedanta Biosciences.

The team identified and characterized a consortium of human-derived bacterial strains with high potency for suppression of inflammatory responses and established their ability to prevent autoimmunity in models of ulcerative colitis, Crohn's disease, and allergy. Furthermore, the team showed that human subjects with ulcerative colitis showed a tendency towards a deficit of the identified immunoregulatory strains. In previous work published in Science in 2011, Honda's group had zeroed in on a subset of analogous, murine-derived, gut microbes and showed they were responsible for triggering production of regulatory T cells, a key therapeutic target in a number of autoimmune and inflammatory diseases.

"There is an urgent need to develop drugs for poorly served autoimmune diseases," said Dr. Honda. "Discoveries on the role of the microbiome in these diseases are a promising starting point for new therapeutic approaches."

Although a number of probiotic microorganisms have been commercialized, their efficacy in treating human disease has been limited. Typically, probiotics used in foods and supplements have been selected based on their ease of culture and manufacturing, not based on their pharmacological properties, and their presence or absence in human samples has not been strongly associated with disease. In contrast, Honda's team selected bacterial organisms based on their ability to elicit robust therapeutic responses in disease models and focusing on organisms shown to be depleted in human diseases.

The team further showed that the organisms act in concert as a consortium, providing bacterial antigens and short-chain fatty acids that are sensed by the host and mediate immunoregulatory responses. None of the organisms alone was nearly as potent as a consortium of organisms – suggesting that cooperation between the strains is essential to their therapeutic effects.

"We have made a significant commitment to translate research in the microbiome field," said Dr. Ben Shapiro, Board member of Vedanta Biosciences and former EVP Worldwide Basic & External Research at Merck, "identifying specific therapeutic compositions and drilling down to their mechanism of action is a key step towards developing interventions in this new field with pharmaceutical rigor."

About Vedanta: Vedanta is developing a novel class of immunotherapies that modulate the human microbiome. Vedanta was founded by PureTech and a group of world renowned experts in immunology and microbiology including Drs. Ruslan Medzhitov (Yale), Alexander Rudensky (Memorial Sloan-Kettering Institute, Rockefeller University, Cornell), Dan Littman (NYU), Brett Finlay (UBC), and Kenya Honda (RIKEN).

About PureTech: PureTech www.puretechventures.com is a healthcare product innovation company specializing in developing products that will significantly impact human health and well-being. PureTech's pipeline of 15 products includes more than 10 programs at or beyond the stage of human clinical testing.

SOURCE Vedanta Biosciences, Inc.
http://www.appliedclinicaltrialsonl.../ArticleNewsFeed/Article/detail/817718?ref=25

 

[kiny]

Typically, probiotics used in foods and supplements have been selected based on their ease of culture and manufacturing, not based on their pharmacological properties

I've never heard this. The reason they select those probiotics is because of their properties, because you can get them regulated as a food substance, instead of a medical substance, which allows you to bypass regulators.

They can culture anaerobe bacteria like F. Prau too, but it would cost them years and millions of dollars to get it past regulators, since it will regarded as a a medical substance instead of a food additive.

 

[wild_one353]

CD4+ T regulatory cells (Tregs), which express the Foxp3 transcription factor, play a critical role in the maintenance of immune homeostasis. Here, we show that in mice, Tregs were most abundant in the colonic mucosa. The spore-forming component of indigenous intestinal microbiota, particularly clusters IV and XIVa of the genus Clostridium, promoted Treg cell accumulation. Colonization of mice by a defined mix of Clostridium strains provided an environment rich in transforming growth factor–β and affected Foxp3+ Treg number and function in the colon. Oral inoculation of Clostridium during the early life of conventionally reared mice resulted in resistance to colitis and systemic immunoglobulin E responses in adult mice, suggesting a new therapeutic approach to autoimmunity and allergy.

another study-

Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota
Published online 10 July 2013
http://www.nature.com/nature/journal/vaop/ncurrent/full/nature12331.html


This would agree with multiple findings previous findings suggesting these groups of bacteria are involved in the direct causation of IBD, where these bacteria, are under represented, extinct, or missing.The clostridia cluster XIVa are damaged in IBD.

This also agrees with the hypotheisis that the restoration of these species with a fecal transplant, could cure IBD. There is no need to isolate the precise molecules they produce and develop any drugs. This can be cured.

http://www.crohnsforum.com/showthread.php?t=52400