Getting Organ Recipients Off Drugs

Everyday an average of 79 people receive an organ transplant. Organ transplantation is a widely used medical treatment for patients with failing organs; but while the possibility of growing new organs gets closer every day, the 113,433 people on the organ waiting list can't wait for that breakthrough. Instead they have to rely on the generosity and unfortunately, often times the tragedy of others. The organ recipients then spend the rest of their life on immunosuppressant drugs which have a host of side effects including high blood pressure, diabetes, infections, and cancer. A new "cocktail' of cells may aid the post-treatment of organ recipients. By mixing the immune system of the donor and recipient, patients can live without immunosuppressants.

Image credit: dailytech.com

The Problem

Immunosuppressant drugs, also known as Anti-rejection medications, stop the body from rejecting the transplanted organ. They prevent the recipient body from killing the new organ as a foreign invader but they also suppress the patient's own immune system to the point where they can't fight off the bacteria and germs they face every day. Even though organs are closely matched before the transplant, rejection of a new organ can happen quickly or over a long period of time, (also known as chronic rejection). There are many different types of drugs available, but they all act by blocking the immune system so it is less likely to react against the transplanted organ. There are three main immunosuppressant drugs.

· Cyclosporins, which inhibit T-cell activations, thus preventing T-cells from attacking the transplanted organ.

· Azathioprines, which disrupt the syntheses of DNA and RNA and cell division.

· Cortiosteroids, which suppress the inflammation associated with transplant rejection.

Patients are usually prescribed a combination of the drugs listed above after their transplant. And while the doses and combination might change, most patients will be on at least one for the rest of their lives.

The transplant can also fail in patients who were well matched and took all the pills, which can cost up to $25,000 a year.

The Study

The new study was reported on March 7^th in Science Translational Medicine and led by Suzan Ildstad at the Institute for Cellual Therapeutics at the University of Lousiville in Kentucky. The report shows a way to better organ acceptance and minimize the risk of graft-versus-host disease (GVHD). GVHD is a potentially lethal condition in which the donor's immune system may attack the recipient's body. The clinical trial was conducted at Northwestern University in Chicago. During the study, Ilstad and colleagues extracted bone marrow-producing cells from kidney donors. Then the cells that likely cause GVHD were removed and the number of 'facilitating cells", which make and organ recipient's system more receptive, were expanded. The trial used eight patients with severe kidney disease and had taken radiation and drug treatment to suppress their immune system. The radiation and drug treatment is used to 'condition' the body by suppressing the recipient's bone marrow so the donor's cells have room to grow. The patients then each received a kidney from a genetically mismatched relative or unrelated donor; the concoction of donor cells, a bioengineering mobilized product enriched for hematopoietic stem cells and tolerogenic graft facilitating cells, was given a day later.

The donor's immune cells almost completely took over the recipient's immune system, but the new immune system didn't attack the recipient's body. In addition, the body didn't reject the transplanted organ. Of the eight recipients, five were completely off immunosuppressants, with no sign of GVHD, within a year. Their new kidneys have continued to function well for an additional 18 months.

According to Ildstad, the treatment increases the recipient's regulatory T-Cells that serve as 'peacekeepers' by keeping the immune system in balance. "The preliminary results from this ongoing study are exciting and may have a major impact on organ transplantation in the future," said Joseph Leventhal, MD, PhD, transplant surgeon at Northwestern Memorial Hospital and associate professor of surgery and director of kidney and pancreas transplantation at Northwestern University Feinberg School of Medicine. "With refinement, this approach may prove to be applicable to the majority of patients receiving the full spectrum of solid organ transplants."

Image Credit

There are still some drawbacks; replacing the immune system is a drastic step and there is still a chance that GVHD could develop in the future. Since the facilitating cells are patented, the method for producing them is not fully described in the paper making it difficult for other researchers to reproduce the findings to ensure reproducibility of the experiment and consistency in the treatment.

Resources

The Need Is Real: Data- organdonor.gov

Organ Transplantation: The Process- organdonor.gov

Immunosuppressant Drugs- medical-dictionary.com

Northwestern Memorial Hospital. "Doing Away With Anti-Rejection Medication." Medical News Today. MediLexicon, Intl., 9 Mar. 2012. Web.

15 Mar. 2012. <http://www.medicalnewstoday.com/releases/242635.php>