Move Over Probiotics, Coronado Biosciences Has 'Proparasites'

Includes: FBIO
by: Iggy Igette

Not too long ago I had the opportunity to wander around the Amazon Jungle in South America. To prepare for my trip, it was recommended that I get a handful of vaccinations in order to prevent various infections typically found in the "Third World." I was advised to vaccinated for tetanus, yellow fever, typhoid, and viral hepatitis, as well as take anti-malaria pills while there in the jungle.

Click to enlarge all images.

As a society, we've been very successful at improving hygiene as well as medication treatments against infections. A simple look at the elimination of small pox infections and the decrease in cases of polio, measles, and a number of parasitic infections in our world and man can claim victory over "the bugs."

Let's take a look at our "victory Map" against a type of intestinal parasites called helminths. Advances in medicine and hygiene, particularly in North America, Europe, Australia, and the former Soviet Union, have kept the worms at bay. In developing third world countries and continents -- South America, Africa, Southeast Asia, etc. -- the worms continue to thrive. Also note that these worms tend to be more prevalent closer to the equator where tropical, warm environments are most suited for their comfort.

While most of us in the industrialized countries can claim success in eradicating worm infections from our list of daily worries, over the years we have replaced one set of medical problems for another group of medical problems -- autoimmune diseases. In the U.S. there are over 100 immune-system-related conditions affecting over 50 million Americans -- a quick look at the chart below shows that the numbers are rising at an alarming rate. Some of the most severe, debilitating chronic conditions of our times include multiple sclerosis, inflammatory bowel disorders (Crohn's disease and ulcerative colitis), Type 1 diabetes, and asthma -- all of which are autoimmune conditions.

Autoimmune conditions are highest in the developed world: North America, Europe, Australia, and Japan. Now why is it that the "advanced countries" are plagued with these autoimmune conditions while the "dirty, unhygienic" parts of the world "full of parasites and worms" have a very low incidence of autoimmune disorders?

If we place the two images of autoimmune disorders and worm Infections side by side, it looks fairly interesting. It seems that when man and worm live side by side (or, more accurately, worm lives inside of man), there seems to be some mutually beneficial health effects when it comes to autoimmune disorders.

Why is this? To understand this apparent symbiotic relationship better between worm and man, it's first important to understand what an autoimmune condition is. In simple terms, an autoimmune condition is when the immune system gets confused and rather than attacking the "bad guys," it attacks itself. For example, if the immune system attacks certain areas of the pancreas, the person develops Type 1 diabetes. If the immune system attacks certain areas of the central nervous system, the person develops multiple sclerosis. If the immune system attacks particular areas of the intestines, we call that an inflammatory bowel disorder (Crohn's disease and ulcerative colitis).

So why do those who live in areas of poor sanitation, impure food, and crowded third world conditions seem to have lower risks for autoimmune disorders? Based on an ongoing hypothesis called "the hygiene hypothesis," exposure to/infections from parasites can be a mutually beneficial situation. After all, man and worm have lived together for many centuries before we developed better hygiene and antibiotics, as well as anti-worm medications. The worms, in order to protect their own survival inside man's intestines, have somehow been able to "regulate" our immune system to prevent it from being confused and attacking itself (autoimmune disorders) as well as attacking the worm. A dead host = a dead worm.

So if the worms protect both man and their own survival by regulating the human immune system, what happens when we take away the worms? One would assume that the beneficial regulation of the immune system goes away and the incidence of autoimmune disorders increases.

So how do we prove this seemingly barbaric theory that parasites may actually be beneficial for humans? Particularly in humans afflicted with autoimmune conditions?

Well, there's a straightforward way to test the theory. Take a number of folks with autoimmune conditions, give them a predetermined dose of "worm" at a predetermined frequency, and record what happens to them. It's called a clinical trial.

There's a "worm-focused" company called Coronado Biosciences (CNDO). It has rights to a pig whipworm egg called Tricuris Suis Ova, or TSO. As of now the company has completed four Phase I clinical trials with TSO. A number of photos here can be viewed on the company's website.

Let's take a look at a few published studies using TSO in treating autoimmune conditions. Note that these are relatively small studies -- Phase I clinical trials.

TSO And Crohn's Disease

29 patients with active Crohn's disease (defined by a CDAI > 220 score -- an objective measure of Crohn's disease activity). Patients took TSO eggs (2,500 eggs) in a solution every three weeks for 24 weeks. Patients maintained diaries of symptoms, and disease activity was measured by CDAI. At 24 weeks, treatment with TSO was associated with significant improvement: 79.3% patients experiencing a response (decrease in CDAI > 100 points, or CDAI < 150) and 72.4% achieving remission (CDAI < 150). There was no severe side effects of TSO reported.

Coronado announced plans to begin a Phase II trial in Crohn's involving around 200 patients.

TSO And Ulcerative Colitis

This randomized, double-blind, placebo-controlled study evaluated TSO in 54 patients with active ulcerative colitis (determined by the ulcerative colitis disease activity index). Clinical trial duration was 24 weeks (treatment arm and placebo arm with crossover phase). Without going into the complicated details of the trial design, the results (see the graph below) show the difference in positive treatment response between the TSO group vs. the placebo group. The worm TSO group had a more-than-doubled percentage improvement compared with the placebo group.

TSO and Multiple Sclerosis

This was a small yet exciting study reported in 2011. Multiple sclerosis affects approximately 400,000 Americans -- every week about 200 people are newly diagnosed with MS. MS symptoms can include blurred vision, loss of balance, poor coordination, slurred speech, tremors, numbness, extreme fatigue, problems with memory and concentration, paralysis, and blindness. There is no cure. MS is typically diagnosed using an MRI scan that reveals MS brain lesions in the brain (and often in the spinal cord).

In this study at the University of Wisconsin, five newly diagnosed and untreated MS patients (relapsing remitting category) were given TSO orally every two weeks for three months. After three months the mean baseline number of MS brain lesions decreased from 6.6 to 2.0. Two months after TSO was discontinued the mean number of lesions rose back up to 5.8 lesions. No significant adverse side effects were noted. These first five patients represented the first part of a two-part study. Additional patients are currently being studied for up to 10 months, with results to be reported in 2013.

Below is a study showing the number of MS "exacerbations" (symptoms that flare up) comparing a group without TSO (uninfected) to a group with TSO (infected). The TSO group had no significant MS flareups until they were "treated" to eradicate the TSO -- at which time their MS symptoms flared back up again.

Coronado plans to initiate a Phase II study on MS involving approximately 200 patients. By the end of 2012, a total of 18 clinical trials would be completed, on-going, or planned involving around 1,000 patients.

From a business perspective (U.S./Japan annual market sales), ulcerative colitis is a $1 billion market, Crohn's disease a $2.4 billion market, and MS a $5.4 billion market.

For those who are wondering how Coronado Bioscience decided to use the pig whipworm egg instead of the many other worms and parasites out there, the reasons are outlined below.

Here's a look at the company's pipeline with regard to TSO for the treatment of AML (a type of deadly leukemia), multiple myeloma, etc.:

Here's a look at Coronado Biosciences' 2012 milestones and developmental timeline:

Here are the various studies in progress (or planned) using TSO:

Our parents and grandparents used to say that letting kids play in the dirt would boost their immune system. Perhaps they knew something we didn't.

Disclosure: I am long CNDO.