A team of researchers at the U of M have revived an ancient medical treatment to address a severe gastrointestinal illness and have developed ways to standardize the procedure.
The process, dubbed “fecal microbiota transplantation” transfers healthy bacteria from one person’s intestine to another person where the healthy bacteria have been depleted. It’s very effective for people suffering from Clostridium difficile, also called C. diff, an opportunistic pathogen that takes over when antibiotics wipe out “essential and symbiotic” bacteria in the gut.
Although the infection itself is triggered by antibiotics, the standard treatment for C. diff has been to give even more antibiotics, which can trigger a vicious cycle of recurrent C. diff. Normally, C. diff can be held at bay by resident bacteria in the colon. When antibiotics kill off the normal bacteria, C. diff flourishes, releasing toxins that cause diarrhea, fever, nausea and abdominal pain. Subsequent courses of antibiotics suppress, but don’t kill C. diff, and it often reemerges. In severe cases, patients can waste away and die.
A Mutant Monster of Our Own Making
Fecal microbial transplantation is effective in treating refractory C. diff infections. The donor feces contain healthy populations of bacteria that repopulate the gut, and hold C. diff in check. However, explains Alexander Khoruts, M.D., associate professor of medicine at the University of Minnesota, the current process is unpleasant and unregulated. Essentially, a donor must provide feces which are implanted via colonoscopy, nasal tube or enema.
“In this form, the treatment has a long history. It goes back as far as 4th Century China, and was introduced into Western medicine by Dr. Eisemann and his team in 1958. Surgeons trained in 1960s remember Dr. Wangensteen using the procedure at the U of M. (Wangensteen was chairman of the U’s Surgery Department from 1930 to 1967.) Then we learned how to treat C. diff with antibiotics. However, the organism has since evolved, acquired more resistance to antibiotics and has become even more toxic.”
Khoruts and colleague-collaborator Michael Sadowsky, director of the U’s Biotechnology Institute, have recently invented a process that is more reliable and can be standardized, making the treatment more widely available to patients suffering from C. diff.
Their invention is just in time, because C. diff infections have surged over the past decade. The tenacious and deadly illness now affects about 340,000 people each year. In fact, explains Sadowsky, “On average, patients have had the infection for up to a year with six relapses. Estimates are that 14,000 to 30,000 people die each year from it. The percentage of recurrence of C. diff is twenty to thirty percent. With each course of antibiotics, the subsequent relapse goes up another twenty to thirty percent.”
Care is estimated at $2,500 to $7,000 per patient. In some cases, colectomy is necessary. The infection, traditionally confined to hospitals and nursing homes, is now spreading into the community.
Fortunately, the process Khoruts and Sadowsky have invented is a likely candidate for broad medical use. The team was the first to document that the transplanted bacteria actually survive in the new host (the patient), according to Khoruts. This helps build credence for the treatment. It is 92 percent efficacious and is vastly superior to the antibiotic suppression method. And the standardized, streamlined method will make the application more likely to be approved by the FDA.
Sadowsky adds, “In the old practice, feces were directly transplanted. Our innovation is in separating the bacteria from the donor feces, freezing it, and providing in essence a universal material for use in patients. Our donors have been tested for disease, and we use the same paradigm as blood donation, with some additional restrictions. For example, we don’t accept anyone using a prescription medication or who has been traveling abroad.”
Process Recently Licensed
CIPAC Limited, an Australia-based company with subsidiaries in California, is working with the U of M to advance the technology and bring a safe, effective treatment to market. It has licensed the technology and is working with the FDA and the university’s team to begin clinical trials.
The FDA’s recent announcement should accelerate interest in the process. Khoruts notes, “Our group has been the leader in standardization of this procedure in the U.S. We have been doing it in steps and our latest advance is moving material preparation out of the research laboratory to an FDA-registered facility at the university where the process is done in accordance with the FDA’s GMP (good manufacturing practices). We think that this is how the procedure will continue to develop. In the short term the FDA involvement very likely will result in decreased access to this procedure. However, once the process is streamlined, as we’re trying to do, it will become part of mainstream medicine and access will become greater than before.”
Post by Vincent Hyman, a freelance writer based in St. Paul, Minn.
Originally published on Research @ the U of M.