Monthly Archives: July 2014

Clostridium difficile Research and Development Community June - July 2014

laboratorybeakers

Here’s the latest from the Clostridium difficile research community:

Two of the leading symptoms associated with Clostridium difficile infection in the intestine are colitis and pseudomembranous colitis. In this paper, the authors study the role of GM-CSF, an inflammatory cytokine, using a neutralizing monoclonal antibody. It was found that treating mice with an anti-GM-CSF mAb did not affect C. difficile colonization levels but did reduce the expression of the neutrophil chemokines CXCL1 and CXCL2. In addition, there were reduced numbers of neutrophils in histology sections and reduced expression of SLPIs, secretory leukocyte protease inhibitors. The authors conclude that GM-CSF is involved in the signaling network associated with neutrophil recruitment but does not have an effect on the elimination of infection.

https://www.landesbioscience.com/journals/gutmicrobes/article/29964/?nocache=794108227

In this paper, the serum levels of antibodies of patients with a single episode of CDI are compared to the levels of patients who have had a recurrence of CDI to determine if lower serum concentrations of anti-TcdA and anti-TcdB antibodies correlate with a higher risk of recurrence. The authors examined the IgA and IgG antibody levels against the two major toxins and against non-toxin cell surface antigens in serum. They found that advanced age and low serum concentrations of anti-toxin antibodies are associated with recurrence but anti-cell surface antigen antibodies were not. The authors also note that serum TcdB neutralizing capacity was not significantly associated with recurrence of Clostridium difficile infection.

http://onlinelibrary.wiley.com/doi/10.1111/1469-0691.12769/abstract;jsessionid=D532390E50ED61A88A1E011B8EE768A6.f04t02

Disturbance of a host’s natural intestinal microbiota by means of antibiotic intake, most commonly after hospitalization, makes a patient susceptible to colonization of Clostridium difficile and prone to CDI. In this paper, the authors use the lethal enterocolitis model in Syrain golden hamsters to evaluate changes in intestinal microbiota following a dose of Clindamycin. Using 16S ribosomal RNA analysis and sequencing, it was found that there were drastic changes in fecal microbiota, particularly involving the phyla of Bacteriodetes and Proteobacteria. The authors mention that the host’s gut microbiota produces certain soluble factors that may be involved in the interruption of the growth of C. difficile.

http://www.nature.com/ismej/journal/vaop/ncurrent/full/ismej2014127a.html

Although toxin-neutralizing epitopes have been found on the receptor-binding domains (RBD) of Toxin A and Toxin B, which have gained attention since they are viable vaccine targets, the authors of this paper evaluate the potential of DNA vaccination against CDI. Highly optimized plasmids that encode this receptor-binding domain were created and introduced to mice and non-human primates intramuscularly. It was found that this immunization significantly increased the levels of both anti-RBD antibodies and RBD antibody secreting cells. In addition, the immunized mice were protected from a lethal challenge of purified toxins and from a challenge with C. difficile spores from UK1 and VPI 10463 strains.

http://iai.asm.org/content/early/2014/07/08/IAI.01950-14.long

Cwp84, a surface-located cysteine protease, is responsible for the post-translational cleavage of SlpA, a surface protein, into subunits during S-layer biogenesis. In this paper, the first crystal structure of Cwp84 is illustrated at a 1.4 Å resolution. The authors identify the important structural components of the enzyme and give insight to the role of Cwp84 in C. difficile S-layer maturation.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4089489/

Alanine racemase (Alr) is a PLP-dependent enzyme that catalyzes the reversible racemization of L- and D-alanine, an important part of the peptidoglycan cell wall of bacteria. Being that there are no known alanine racemase homologue in humans, the authors of this paper decided to test it as an antibiotic target. In this paper, the catalytic properties and crystal structures of alanine racemase from Clostridium difficile 630 are evaluated, the first steps towards Alr structure-based therapeutics for CDI.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4089486/

 

Chandrabali Ghose-Paul,MS,PhD, Chairperson of Research and Development

 

C. difficile infection, C Diff Foundation’s “Raising C Diff Awareness” program offered

It is with great pleasure to share the news that the C Diff Foundation’s, “Raising C Diff Awareness” program is being offered to over 500 facilities and 1,000 members of the Florida Health Care Association. On-site scheduling is in progress and can be arranged by contacting the C Diff Foundation office toll free at:

1 - 844 - FORCDIF

Established in 1954, Florida Health Care Association is celebrating its 60th anniversary in 2014. FHCA is a federation representing over 1,000 members and over 500 facilities which provide skilled nursing, post-acute and sub-acute care, short-term rehab, assisted living and other services to the frail elderly and individuals with disabilities in Florida. FHCA membership also includes more than 400 Associate Members, or companies, that provide valuable products and services to long term care providers.

FHCA_60thAnniversaryLogoA(2)

FHCA is the state affiliate of the American Health Care Association/National Center for Assisted Living in Washington, DC. Governed by a Board of Directors, the mission of FHCA is to advance the quality of services, image, professional development and financial stability of its members. FHCA maintains reimbursement, regulatory, clinical and media/public relations experts on staff and makes its legal, business and labor consultants available to all members. FHCA members benefit from a strong, unified presence in the state Capitol, quality improvement and survey support, up-to-date information and continuing education opportunities. Together, these member services work to support member providers and assist the interests of government, the greater health care community and the general public.

To become a member or for additional FHCA information please visit their website:

http://www.fhca.org

C. difficile treatment in clinical testing; Seres Health receives Notice of Allowance from U.S. Patent and Trademark Office

*In The News* Seres Health, a clinical-stage therapeutics company developing novel treatments for diseases related to the human microbiome, today announced that it has received a Notice of Allowance from the U.S. Patent and Trademark Office for a pharmaceutical composition patent application that covers its lead product candidate, SER-109, which is currently in clinical testing for the treatment of recurrent C. difficile.

The patent to be issued from this allowed application entitled “Synergistic Bacterial Compositions and Methods of Production and Use Thereof” carries a patent term to at least 2033, and specifically claims therapeutic compositions of bacterial populations that are cytotoxic or cytostatic to pathogens, including in combination with anti-bacterial, anti-fungal, anti-parasitic and anti-viral agents. Similar applications have been filed with the Patent Cooperation Treaty (PCT).

“This notice of allowance is an important step forward not only for Seres but for the microbiome field in general,” said Dr. Roger J. Pomerantz, President, CEO and Chairman of Seres Health. “We are driven to obtaining strong patent protection for SER-109, as well as our other clinical candidates, as we continue development with the goal of bringing our first-in-field product to patients.”

The forthcoming patent, published as US Patent Publication 20140147425, is the first to emerge from the company’s patent portfolio that includes over 30 applications. Utilizing its proprietary platform for microbiome-based drug discovery, Seres rationally designs therapeutics based on the ecological nature of the microbiome, catalyzing a shift from a diseased microbiome to one of health. SER-109, the first Seres Ecobiotic® product tested in clinical studies, has demonstrated clinical efficacy for recurrent C. Difficile infections. The company is rapidly growing its pipeline of Ecobiotic® therapeutics for other indications.

About SER-109

SER-109 is the first Seres Health Ecobiotic® product currently in clinical testing for the treatment of Clostridium Difficile Infection (CDI). SER-109 was developed utilizing the Seres Health Microbiome Therapeutics™ platform to understand the ecologies of disease associated with CDI and identify an efficient means to catalyze a shift to health. CDI is a rapidly growing problem associated with antibiotic use. Over 700,000 cases of CDI are reported each year, leading to more than 250,000 hospitalizations and over 14,000 fatalities annually in the U.S. alone. Over 200,000 of these patients have at least one recurrence, for which no drugs are currently approved. SER-109 has demonstrated clinical efficacy, and a late-stage trial is expected to start by the end of 2014.

About Seres Health

Seres Health is a clinical-stage therapeutics company focused on discovering and developing Ecobiotic® therapeutic products, novel drugs to treat important diseases by targeting the underlying biology of the human microbiome. Founded by Flagship VentureLabs™, Seres is pioneering the first therapeutics that catalyze a shift to health by augmenting the biology of the microbiome. Current candidates span infectious, metabolic, and inflammatory diseases. Seres recently announced a research agreement with Mayo Clinic and has received over $20 million in funding to date. For more information, please visit www.sereshealth.com.

 

For article in its’ entirety please click on the following link:

https://ca.finance.yahoo.com/news/seres-health-announces-allowance-key-134200777.html