Diabetes, the Hygiene Hypothesis, and Worms
In 2010, an article published in Clinical & Experimental Immunology, titled "The 'hygiene hypothesis' for autoimmune and allergic diseases: an update," described that the decreasing incidence of infections in Western countries and, more recently, in developing countries, is at the origin of the increasing incidence of both autoimmune and allergic diseases. The hygiene hypothesis is based upon epidemiological data, particularly migration studies, showing that subjects migrating from a low-incidence to a high-incidence country acquire the immune disorders with a high incidence at the first generation. Proof of principle of the hygiene hypothesis is brought by animal models and, to a lesser degree, by intervention trials in humans.
Underlying mechanisms are multiple and complex. They include decreased consumption of homeostatic factors and immunoregulation, involving various regulatory T cell subsets and Toll-like receptor stimulation. These mechanisms could originate, to some extent, from changes in microbiota caused by changes in lifestyle, particularly in inflammatory bowel diseases, but also Type 1 diabetes. Taken together, this data opens new therapeutic perspectives in the prevention of autoimmune and allergic diseases.
In a 2009 article for the New York Times, Jane Brody wrote, "In studies of what is called the hygiene hypothesis, researchers are concluding that organisms like the millions of bacteria, viruses and especially worms that enter the body along with 'dirt' spur the development of a healthy immune system. Several continuing studies suggest that worms may help to redirect an immune system that has gone awry and resulted in autoimmune disorders, allergies and asthma." Brody must have been looking through a crystal ball, because worms have recently hit the news in regard to research on Type 1 diabetes. The preliminary discoveries found in the hygiene hypothesis gave researchers insight into something more unique when thinking about disease prevention.
Parasites, known as helminths when located in the intestines, are the worms referenced by Jane Brody. Helminths are invertebrates that are characterized by elongated, flat or round bodies. Helminths appear to have three major effects on the immune system. They seem to cause changes that activate and increase in number our regulatory T-cells, which dampen immune responses and curb autoimmunity. Helminths also seem to influence other cells that help prevent the "switching on" of effector T-cells that normally cause systemic inflammation and disease within the human body, reflected by lower amounts of pro-inflammatory cytokines such as TNF-alpha. And, helminths also encourage diversity in the gut, improving the state of the microbiome.
Scientists are developing a potentially safe and effective treatment to treat chronic conditions, like Crohn’s disease, ulcerative colitis, MS and Type 1 diabetes using a new drug called TSO, Trichuris suis ova. In plain language, TSO are pig whipworm eggs. The drug consists of purified eggs suspended in a tablespoon of buffered saline solution and swallowed by the patient. The eggs take up residency in the gut without any known harmful side effects. As earthy crunchy as I am, this revelation about worms left me squirming in my seat. That said, I felt to give this topic better understanding, I should go to the source and find out more about what this research means for people with Type 1 diabetes.
Coronado Biosciences is the company that is spearheading the development of TSO. I asked Karin Hehenberger, M.D., Ph.D., Executive Vice President of Scientific Affairs at Coronado Biosciences, to get down and get dirty on the science behind TSO.
Dr. Hehenberger, can you give us your personal story with Type 1?
At Coronado Biosciences, we have been pursuing research using TSO, but it isn’t just research to me—I have a personal interest too. I was diagnosed with Type 1 diabetes when I was 16. I was hospitalized and put on insulin immediately. It really was a big life-changing moment, especially as a teenager, with a very active lifestyle and not having known disease before. I had diabetes for almost 20 years before I started developing serious micro vascular complications, including kidney and eye complications. I need serious treatments such as blood pressure meds, laser therapy for my retinas and a complete focus on excellent metabolic control. Unfortunately, these measures were not enough, and my kidneys went below 10 percent total function, and every day was a struggle. I was facing dialysis but, luckily, my father gave me one of his kidneys, and I immediately felt better. However, the brittle diabetes was still present, and I struggled with hypoglycemia almost daily.
I was offered a pancreas transplant to prevent the new kidney from being destroyed and, more importantly, to help me avoid serious hypoglycemic events which had already rendered me unconscious on several occasions. Every day I wake up and am grateful to my father who saved my life, the family who allowed for the pancreas to be donated, and the wonderful surgeons and nurses who are my heroes! These experiences taught me what it means to live with diabetes, its complications and the fear of losing control due to low blood sugar.
I studied medicine and did my Ph.D. in molecular biology with a focus on diabetes. I believe people should be treated holistically, and especially in diseases such as diabetes, which affect the entire body and people’s behavior. I was definitely driven by a desire to cure, treat and prevent diabetes my entire career and I believe I am in a place right now where I can add value to people with the disease, and those who have yet to develop it.
Is this research only viable for people with a positive test for the antibody, or will it help someone, like you and me, with long-term diabetes?
While our studies with diabetes are still in the early stages, we are trying to do two things: first, we want to identify patients before they have high blood sugar and before the beta cells have been destroyed. As you are probably aware, once beta cells are gone, there isn’t much that can be done to make them come back. The second approach we are taking is to treat people who have already developed diabetes. In the very early stages of diabetes, there is a so-called “honeymoon period,” when there are still beta cells that can produce insulin.
Since the research suggests helminths could help reduce inflammation in the body, would there be any relevance to the research for those who have complications?
In people with already diagnosed diabetes, we do not believe our product can reverse the disease completely. We hope that TSO will halt the immunological destruction of beta cells, and thus improve the symptoms of diabetes, for example, reduce the number of hypoglycemic episodes, and the times a person goes very high in sugar. TSO in this case would aim to maintain existing beta cell function, instead of going from 10-20 percent beta cell function to 0 percent and having higher risk of complications.
Most animals have to have a preventive to keep from being infected by whipworm. Do you kill off the whipworms created by the TSO at some point?
It is important to note that TSO are pig whipworm eggs, and not human whipworm eggs; therefore, the ova cannot grow into worms and colonize in a human. In fact, if treatment is stopped, within a few weeks the worm eggs are no longer present in the body.
Does it help with weight loss?
We have not studied TSO for weight loss. In our studies to date, weight loss was not reported as a significant side effect. However, pre-clinical experiments using other helminths have shown that weight can be reduced in those animal models.
If I have to swallow TSO, please tell me that the solution tastes like grape juice, or a dirty martini!?
TSO is 7,500 ova suspended in a clear, odorless, tasteless saline solution. It is basically like a small shot of water. You can’t see the eggs—they are microscopic. So people who have taken TSO say it goes down very easily!
The human body is an extraordinary thing; complex, creative and resourceful. It is research like this that could lead to fostering better options for management of diabetes and, in the case of someone dealing with microvascular complications, it could reduce the possibility. I, for one, am all for that!