Physorg

A small group of patients with multiple sclerosis were enrolled in a new pilot clinical trial to test bone marrow stem cell therapy at Frenchay Hospital. The aim of the trial is to find out what effects, good or bad, it has on patients with MS, and their disability. It is being conducted by the University of Bristol and North Bristol NHS Trust.

Bone marrow is of great interest to those working to develop new treatments for many diseases, including those affecting the nervous system since the marrow is known to contain stem cells capable of replacing cells in many types of tissues and organs.

Until now, patients have not been treated in this manner, but laboratory studies in Bristol and elsewhere have worked with similar cells to determine potential benefits to aid repair in multiple sclerosis.

The trial is being led by the University of Bristol and Neil Scolding who is a Professor of Clinical Neurosciences for North Bristol NHS Trust.

He said: “We believe this form of adult stem cell treatment, carried out in collaboration with colleagues in the Bone Marrow Transplant Unit at the BRI, will be safe and well-tolerated but, because patients with MS have never had this treatment before, safety has to be proven before any further studies of larger numbers of patients can take place.”

“We will therefore be monitoring this small number of patients extremely carefully over the next 9-12 months. Provided, as is envisaged, we do not find serious adverse effects, we hope to raise the funds to undertake a larger study to examine the effectiveness of such treatment in MS.”

To determine general fitness and degree of disability from MS, patients meeting the initial entry criteria were assessed in the Neurology department and the Burden Centre at Frenchay Hospital.

Frenchay and also at The Hammersmith Hospital in London, various types of brain scans were conducted. Then the patients underwent bone marrow collection under a short general anesthetic at the Bone Marrow Transplant Unit at the BRI.

Via a vein in the arm, the stem cells are delivered back to the patient later the same day after they have been processed from the marrow.

A range of various monitoring tests and scans at Frenchay and in London are then carried out over the following weeks and months.

A small group of patients with multiple sclerosis were enrolled in a new pilot clinical trial to test bone marrow stem cell therapy at Frenchay Hospital. The aim of the trial is to find out what effects, good or bad, it has on patients with MS, and their disability. It is being conducted by the University of Bristol and North Bristol NHS Trust.

Bone marrow is of great interest to those working to develop new treatments for many diseases, including those affecting the nervous system since the marrow is known to contain stem cells capable of replacing cells in many types of tissues and organs.

Until now, patients have not been treated in this manner, but laboratory studies in Bristol and elsewhere have worked with similar cells to determine potential benefits to aid repair in multiple sclerosis.

The trial is being led by the University of Bristol and Neil Scolding who is a Professor of Clinical Neurosciences for North Bristol NHS Trust.

He said:

In order to decrease the risk of immune reactions common in patients undergoing blood and marrow transplantation researchers have taken steps to determine the safety and optimal dose of T regulatory cells (T-regs) at the University of Minnesota.

The groundbreaking clinical trial is being conducted with the hope that it will offer a potential new paradigm for treating autoimmune diseases as well as improve overall survival rates for blood cancer patients.

“Toward our quest of making transplants even safer for adults and children with leukemia, lymphoma, multiple myeloma, and other blood and marrow disorders, we are exploring the possibility of using T-regs to enhance the rate of blood and marrow recovery and reduce the risks of graft-versus-host disease, a complication that affects more than 60 percent of patients,” said Claudio Brunstein, M.D., principal investigator of the study.

Normally responsible for regulating the body’s immune responses, T-regs are a type of lymphocyte or white blood cell. Helping to ward off life-threatening graft-versus-host-disease (GVHD), donor T-regs may suppress the recipient’s immune system so that the healthy donor’s blood-forming stem cells and immune cells can grow in transplant cases. When donated cells attack the body of the transplant recipient it is referred to as GVHD. Following transplant, GVHD is responsible for one-third of the deaths.

The risk of GVHD decreases and the chance of blood and marrow recovery increases when T-regs are infused after transplant. This has been proven by researchers using animal models.

“Once we identified that T-regs were highly effective in mouse models, we then spent three years finding ways to make this therapy valuable for transplant patients and potentially useful for patients with autoimmune diseases,” said Bruce Blazar, M.D., director of the Center for Translational Medicine at the University.

Since they are easier to expand in culture prior to treatment and occur in higher frequency than what is typically found in most adults, the T-regs in this study are isolated from umbilical cord blood (blood collected from the placenta or afterbirth after the birth of a child). This unique use of umbilical cord blood derived T-regs marks a world first for human clinical trials.

Using patients who are undergoing a double umbilical cord blood transplant for bone marrow failure, leukemia, or other blood cancer; this trial is designed to find the highest possible safe dose of T-regs in these immune suppressed patients. There should be no acute side effects with the T-regs according to researchers who have observed similar results already in animal models.

T-regs will be a powerful therapy to enhance engraftment in transplant patients and prevent GVHD if the data in humans mimics animal models. Conditions such as multiple sclerosis, type I diabetes, and other autoimmune diseases will be treated with the T-regs to test for effectiveness once initial efficacy and safety data is known. The cell may help prevent disease progression if T-regs are transplanted early in the life of the disease hypothesized university researchers.

“This is an exciting time. In the near future, I anticipate being able to combine immune cell populations, like T-regs, that stop immune reactions responsible for autoimmune diseases like diabetes, and immune responses to stem cell infusion given to repair already damaged tissues. This brings great hope not only for adults and children with cancer but many other diseases as well. At the close of this clinical trial, we hope to go right to our first clinical trial with T-regulatory cells in the treatment of newly diagnosed diabetes,” said John E. Wagner, M.D., director of the pediatric hematology-oncology and blood and marrow transplantation program at the University of Minnesota.

The Children’s Cancer Research Fund, the National Marrow Donor Program, the Leukemia and Lymphoma Society, the National Institute of Allergy and Infectious Diseases, the National Heart Lung and Blood Institute, the National Cancer Institute, and the National Institutes of Health are funding the study.