Tranzyme Pharma & the FDA were not happy with the results of the Phase III trial results for Ulimorelin. Ulimorelin is similar to Tranzyme’s other drug TZP-102, in that it uses a ghrelin receptor agonist to stimulate motility in the gut. The drug was meant to treat people with delayed gastrointenstinal recovery / post operative ileus which is most often associated with gastrointestinal or gynecological surgery.

Currently the only drug available for delayed GI recovery/post operative ileus appears to be Enetereg(Alvimopan) by Cubist Pharmaceuticals. It is a mu-opioid receptor antagonists, which looks to be designed more to block the effects of opioid based painkillers, which often have a constipating effect & can cause bowel obstructions in patients who are recovering from such surgeries. Enetereg is for short term use and does appear to have risks & side effects associated with it, some of which could be serious such as increased risk for heart attack.

Ulimorelin was meant to accelerate motility in the gut allowing people to move to solid foods & leave the hospital quicker. Unfortunately the official Phase III trial results did not show improvement over placebo. One analyst thinks that there may have been issues with how the results were interpreted & that Ulimorelin may not have been useless after all.

Another set of Phase III results should be made available at the end of the Q2 2012, however Tranzyme is apparently sweeping Ulimorelin under the rug and moving their focus over to TZP-102. Tranzyme took a hammering on their stock when the Ulimorelin results became public, losing almost 50% of their value. They are on the rebound though & hopefully will have better results with TZP-102.

I’ve covered Tranzyme’s TZP-102 before but the basics are that it stimulate’s receptors that are in charge of releasing the hormone ghrelin into the gut. Ghrelin can stimulate the gut and helps us feel hungry.

USDA testers found the infected cow while doing regular testing. The cow had died before the tests were done, but according to it’s owner it was not exhibiting symptoms of Mad Cow Disease beforehand. USDA testers have said that the cow was infected with an atypical form of Mad Cow Disease which was not obtained from eating infected cattle feed.

The infection was found while testing dead cows that were brought to the USDA’s Hanford, California testing facility. It is unclear if other cows from the dead cow’s herd were infected. The current theory is that this infection was a random mutation within the cow & did not infect others.

Currently the USDA is saying that the finding is nothing to be concerned about and are assuring people that dairy & meat are safe to eat. It does appear they are continuing to investigate the findings. The UK has not expressed concern over USA meat, while some South Korean stores have pulled USA beef temporarily.

Mad Cow Disease or bovine spongiform encephalopathy(BSE) is known for the devastating effects it can have on both cow’s & human’s. Human’s that eat an infected animal can develop Creutzfeldt-Jakob disease. Both diseases cause deterioration in metal function & motor skills. The diseases are almost always fatal & do not have effective treatments. They can develop randomly from mutation or from eating an infected animal.

Most people know of Mad Cow Disease from the large outbreak that occurred in the UK during the 80s & 90s. While there was never a massive outbreak in the US, the outbreak did highlight the feeding practices of beef & dairy cattle in both countries. It was revealed that the cows were effectively cannibals due to feed manufacturers putting all sorts of cow parts into their products. Since then reforms have been made to avoid feeding cows to other cow, however some other animal proteins are still allowed such as milk & eggs along with gelatin & hydrolysed protein from non-ruminent animals.

• USDA Statement
• UK BSE Feed Ban Q&A
• US GAO Feed Ban Critiques

The researchers were specifically interested in studying human umblical cord mesenchymal stem cells which have a poor immunogenic response. This means they are less likely to trigger the immune system into attacking them. At the same time mesenchymal stem cells have potent immunosuppressive qualities, in that they suppress the autoimmune system response. Given these properties, they are being investigated extensively for treatment in those who have autoimmune related diseases.

The researchers in this study induced colitis in mice via trinitrobenzene sulfonic acid. They then transplanted human umblical cord mesenchymal stem cells into the mice. The mice were monitored while alive via immunofluorescent microscopy. The stem cells were shown to have migrated to the inflamed colons of the mice & effectively treated the colitis. Further examination also showed lowered levels of the inflammatory messengers “cytokines” , specifically Interleukin-17,  Interlukin-23, Interferon-γ & Interleukin-6 which have been indicated in previous Inflammatory Bowel Disease research.

Steam cells appear to be a promising treatment option, but marketable treatments are still a ways off in the future.

Research was done at the Institute of Hematology, Chinese Academy of Sciences and Peking Union of Medical Sciences lead by Dr. Zhong Chao Han. Study

The Patient Protection and Affordable Care Act aims to give individuals and businesses access to healthcare exchanges that allow them to browse competitively priced healthcare plans. It also limits the ability of health insurance companies to discriminate against people with preexisting conditions. Additionally the act reduces the costs of preventative care, such as physicals, colonoscopies or contraception while also expanding Medicaid eligibility.

While some states are starting to put together their healthcare exchanges in response to the Patient Protection and Affordable Care Act, other states are questioning the validity of the act itself & are taking their case all the way to the Supreme Court.

The main sticking point for those against the Patient Protection and Affordable Care Act is the requirement that all individuals must sign up for insurance or else they will have to pay an additional fee. Some feel this is unconstitutional. Detractors have also pointed to the expanded costs associated with the act. Those costs will be paid by expanded taxes on those making over $200,000, expanded Medicare taxes along with fees assessed to health insurance companies and tacked on to high end insurance plans. Proponents of the act state that these costs will be more than offset by the savings from patients being able to access preventative care, thus reducing the need for very costly emergency services. The act will also limit profit taking by healthcare & insurance providers, hopefully forcing them to focus more on healthcare rather than their bottom line.

One thing that most people can agree on is that healthcare costs in the United States are out of control. Healthcare companies will have to start doing more with less. Immediate options include things like improving patient education so that fewer procedures are needed. For example, educating patients on antibiotic usage could help by reducing the number of antibiotics that need to be prescribed also reducing the chances for so called “superbugs” which become resistant to existing drugs requiring more investment in researching new drugs. Insurance companies have also been emphasising their preventative & general health services, going so far as to offer fitness & nutrition coaching to patients who are not sick so that they stay that way.

Managing health records and doctor performance will also be key in reducing costs. Some providers are investing heavily in healthcare information technology, going so far as to use cloud data techniques for storing medical records. That may cause some people have their own concerns about privacy, which is another topic entirely. Better records management will enable quicker doctor-to-doctor communication reducing the chances of duplicate tests or costly errors. Monitoring doctor performance may help companies remove incompetent doctors, thus lowering malpractice lawsuits & the insurance costs associated with them.  Some performance management tools, such as Halogen Software, can be used for doctor and healthcare professional talent management.

For those who have chronic illnesses Oregon has taken the novel approach of assigning a specific caseworker to these patients. The caseworkers job is to ensure proper communication between different medical providers, avoiding duplicate tests & making sure the patient is receiving proper care. Low cost urgent care centers are also improving efficiencies, such as companies like ZoomCare.

Regardless of the outcome of the upcoming Supreme Court ruling regarding the Patient Protection and Affordable Care Act, changes are coming to healthcare which will hopefully reduce costs, expand coverage & improve outcomes.

The owner of IBS Tales, Sophie Lee, has written a new book called “Sophie’s Story” which chronicles her life dealing with Irritable Bowel Syndrome.

I want to tell the absolute truth about IBS, because the reality of this disorder is so often clouded by embarrassment and myths. Perhaps the most pervasive myth is that IBS means mild diarrhea and nothing more. Many people with no experience of IBS wonder why we have such difficulty in coping with our condition. This book shows why. - Sophie Lee, “Sophie’s Story”

It would appear that “Sophie’s Story” is aiming to be an accurate & detailed account of what life with Irritable Bowel Syndrome is like, even if the truth about IBS isn’t pretty. Her story will probably resonate with many who have had similar frustrating & painful experiences while dealing with Irritable Bowel Syndrome.

Sophie has been kind enough to provide me with a review copy that I will read  & then review at a later date. You can purchase the book right now on Amazon, Amazon UK. For international orders it’s best to check the IBS Tales website for further details.

The researchers focused on intra-epithelial lymphocytes(IELs) which reside just below the epithelial cell layer that makes up the walls of the intestinal tract. IELs play an important role in the immune response to foreign invaders, they are essentially the first line of defense against bacteria trying to setup shop in the intestinal tract or penetrate the intestinal lining. Mice involved in the study were given a specific diet that was devoid of “cruciferous vegetables”. Those given this diet showed a reduction in the number of IELs residing in their gut. They also looked at mice that were genetically modified to not have IELs. Both mice groups showed similar problems with regards to being able to control the microbial flora in their digestive tract as well as showing a slowed ability to heal from damage to the intestinal tract.

It appears that cruciferous vegetables contain compounds which bind to “aryl hydrocarbon receptors”(AhRs) which the IELs express. When these compounds bind with AhRs it promotes the continued growth of IELs. Cruciferous vegetables are largely made up of green leafy vegetables as well as mustards.

Widely available cruciferous vegetables are:

• Broccoli
• Cauliflower
• Cabbage
• Brussel Sprouts
• Collard Greens
• Kale
• Bok Choy
• Rutabagas
• Radish
• Mustard Seed
• Wasabi

Some people with digestive issues have trouble with fibrous plants & care should be taken when adding these plants to a diet that previously did not contain many or any of them. People who cannot tolerate them raw may look to incorporate them into gently cooked dishes.

One thing to note is that the detection of high levels of IELs has often been a hallmark of inflammation. While this doesn’t mean that promoting IELs by eating more vegetables will lead to more inflammation, it would suggest that IELs are not the root cause of Inflammatory Bowel Diseases.

Sources:

• Cell – Exogenous Stimuli Maintain Intraepithelial Lymphocytes via Aryl Hydrocarbon Receptor Activation
• News from Cambridge UK
• Cruciferous vegetables – Wikipedia, the free encyclopedia

Crohnology Social Networking Site

Crohnology is the creation of Sean Ahrens, a twelve-year veteran of Crohn’s Disease & a software developer who works in the San Francisco Bay Area in California. The look of the site is pretty well polished with features that allow you communicate with & find others who have Inflammatory Bowel Diseases. Of particular note is the ability to list treatments you’ve tried & then rate how well those treatments worked for you. The site is currently in private beta mode, but you can request an invitation by going to the website & entering your e-mail address.

IntenseIntestines Social Network

IntenseIntestines was initially a blog site but has recently switched over to a social networking platform. It appears to be more of a community oriented site allowing users to create a custom profile, join groups, post on forums as well as upload pictures & videos. While it may lack the polished look & perhaps more advanced features of Crohnology, it still looks as though it could be a valuable resource down the road as more members join.

As more patients turn from just being “patients” and instead into “patient advocates” tools such as these social network sites will become a valuable resource for patients to help themselves without having to rely so much on the medical community which often times has a cold & distant bed manner. Often patients are in the dark all too often when it comes down to what to expect from certain treatments & all too often the medical community gives them vague or even inaccurate information. Additionally by connecting patients with other patients, new & alternative methods of treatments may spread more quickly thanks to sites such as these.

A recent study published in Gastroengology came to the conclusion that those taking Remicade treatments showed better outcomes & had less chances of needing surgery later, than those taking placebo. While this appears to be good news the trustworthiness of the study might come into question because many of researchers involved disclosed ties to pharmaceutical companies, including the manufacturer of Remicade which was also involved in funding the study.

The FDA also recently announced the approval of Remicade in children ages 6 & older. The approval does come with the stipulation that it be used in children with moderate to severe Ulcerative Colitis who are not responding to other treatment methods. The FDA has given Remicade & similar drugs like Humira “black box warnings” because of the risk of things like cancer, neurological damage & severe infection.

Remicade & Humira are considered Tumor Necrosis Factor(TNF) blockers, specifically TNF-alpha blockers. TNF is a signaling protein that is responsible for part of the immune system & inflammatory process. TNF blockers are derived antibodies, turning these drugs into almost mini-immune systems that seek out a specific target. While blocking TNF can help with inflammatory diseases, the side effects from blocking TNF obviously show that it’s not perfect. The immune system is very complex with many different signaling proteins working together. Future drugs will probably look at targeting different proteins or multiple proteins as well as trying to have a “gentler” overall touch. Due to the complexities involved with generating the antibodies for TNF blocking drugs, the drugs are very expensive costing tens of thousands of dollars per dose.

For many Remicade & Humira have been helpful, but some have been bitten by the serious side effects that they can cause. A woman in Montana sued the manufacturer of Humira over neurological damage to her feet. Recently a Tennessee man claimed Humira caused him to become susceptible to a severe fungal infection. The Crohn’s & Colitis Foundation of America also has a page with information on the cancer risks of TNF blocking drugs.

Those looking into TNF blocker drugs for themselves or someone else such as a child, should read up on the possible side effects & warnings before moving forward with treatment.

Sources:

• FDA approves Remicade to treat ulcerative colitis in children 6 years and older
• Early Mucosal Healing With Infliximab Is Associated With Improved Long-term Clinical Outcomes in Ulcerative Colitis
• MD News – Infliximab Improves Clinical Outcome in Ulcerative Colitis
• Abbott Labs Sued on Claim Humira Caused Lasting Nerve Damage – Bloomberg
• This Drug May Cause… | The Fly-By | Memphis Flyer
• CCFA.org: Cancer Risks to Remicade® and Humira® Explained

The Phase II/III FDA drug trials in the US will be lead by Professor David Y. Graham from Baylor College of Medicine located in Houston, Texas. Professor Graham worked for NASA as a physician during the Apollo program, has written over 800 medical articles & is considered to be one of the “Top 50 Most Influential Gastroenterology Professionals of the 20th Century” as rated by Gastroenterology.com.

“Phase II/III” trials differ from more typical separate Phase II & Phase III trials in that the study is more randomized than a typical Phase II trial, as well as there being more participants involved. This allows data from a Phase II/III trial to be used going forward in a Phase III trial. However, Phase II/III trials require more infrastructure & patients, raising costs. Phase II/III trials could be looked at as though they are Phase III trials with stronger stop parameters than a typical Phrase III trial. Given that the drugs used within RHB-104 have gone through Phase III trials in Australia, this is probably why RedHill Biopharma is confident in moving forward with the Phase II/III style of trial.

RHB-104 is a triple antibiotic formula that is used to treat MAP bacterium. MAP is a shorter way of saying “Mycobacterium avium subspecies paratuberculosis” bacterium. The inception of RHB-104 dates back to the late 1990s with development being started by Dr. Thomas Borody of the Centre for Digestive Diseases.  The three components of RHB-104 are Rifabutin, Clarithromycin and Clofazimine which are all rather common antibiotics, the difference is in using all three, dosage level & duration of treatment.

Dr. Borody has also helped in the development of different triple antibiotic treatments for H. Pylori infections, which is a leading cause of peptic ulcers. One of these treatments was also purchased by RedHill Biopharma which has labeled it RHB-105. I’ve also mentioned Dr. Borody’s work on fecal transplantation / bacteriotherapy which is another treatment Dr. Borody uses for Crohn’s Disease.

What is now known as RHB-104 in the US has been a hot potato throughout the biotech world for over the last decade. The drug formula was initially licensed to a company called Pharmacia, but upon their merger with Pfizer(who did not wish to continue development of the drug), ownership fell back to the Dr. Borody founded company Giaconda under the name “Myoconda”. Finally in August of 2010, RedHill Biopharma purchased the rights to Myoconda for US & European distribution.

RedHill Biopharma does appear to be serious about bringing RHB-104 to market what with the recent exclusive acquisition of a DNA based MAP bacterium infection test that was developed by Dr. Saleh Naser of the biomedical division at the University of Central Florida.

MAP infection appears to be present in about 40 – 50% of those with Crohn’s Disease. MAP bacterium are known to cause Johne’s disease in animals such as cattle. Johne’s disease is an inflammation of the small intestine & can be fatal in some cases. Currently there is no definitive proof that MAP infection is the cause of Crohn’s Disease, the fact alone that not all patients with Crohn’s Disease have MAP infections should highlight that MAP is probably not the sole cause for all patients. It could be the sole cause or at least a contributing factor for some though. The main link between MAP & Crohn’s Disease is from studies showing that MAP infection is more prevalent in those with Crohn’s Disease than in those who have Ulcerative Colitis.

What with concerns over antibiotics causing Crohn’s Disease, some may have worries about this treatment essentially being 3 different antibiotics. I would not be too concerned if someone has already been given a diagnosis of Crohn’s Disease as you cannot change your diagnosis & if you test positive for MAP infection perhaps MAP was more the cause of the disease than antibiotic usage. Of course some could argue that antibiotic usage might lead to more susceptibility of MAP infection. Neither theories are proven though. Perhaps a combination of RHB-104 along with Dr. Borody’s bacteriotherapy could be a likely treatment avenue for those concerned about their digestive bacterial flora’s health post-treatment.

RedHill Biopharma has not released a date for when the trials are too begin, but assigning Professor  Graham as the leader of the study appears to be a step in the right direction.

Sources:

• RedHill Biopharma appoints Prof. David Y. Graham, MD as Lead Investigator for the US pivotal trial with RHB-104
• Giaconda Products – Wikipedia
• Professor patents test for possible Crohn’s disease cure
• Someone’s Experience Taking Anti-MAP treatment
• Mycobacterium avium subspecies paratuberculosis – Wikipedia

The Man Who Couldn't Eat

Food is not just sustenance. It is memories, a lobster roll on the beach in Maine; heritage, hot pastrami club with a half-sour pickle; guilty pleasures, a chocolate rum-soaked Bundt cake; identity, vegetarian or carnivore. Food is the sensuality of a ripe strawberry or a pork chop sizzling on the grill. But what if the very thing that keeps you alive, that bonds us together and marks occasions in our lives, became a toxic substance, an inflammatory invader? In this beautifully written memoir, both gut-wrenching and inspiring, award-winning writer Jon Reiner explores our complex and often contradictory relationship with food as he tells the story of his agonizing battle with Crohn’s disease—and the extraordinary places his hunger and obsession with food took him.

I have not personally read this book yet & I am not sure that I will in the immediate future due to the bad memories I have from my stint of serious Gastroparesis back in 2006. From the description, reviews & the first few pages I’ve read it sounds as though his experience was somewhat similar to mine. The concept of food being poisonous or causing harm is such an alien concept to most. Our society literally runs on food. You really do not notice how many food commercials there are or how there are one or more restaurants or food stores practically every block, until you’ve been robbed of the ability to eat. When eating makes you ill, it turns your life into a paradox, you must eat to live but eating almost seems to be killing you. It doesn’t just take a toll on you but on those around you who are unable to change your predicament.

I am not sure I’d recommend the book to those currently suffering through a bad digestive illness, although it might provide an avenue of sympathy, someone who has been there, who understands. To those who are in the good graces of the digestive gods it might do them good to read the book & count their digestive blessings even if the subject matter causes some indigestion.

You can pick the book up at your local bookstore or on Amazon. You can also read the first couple of pages on Amazon.com as well.