Miami, FL (May, 1998) – Jackie Warren Demijohn has made medical history in the diabetes world. She, along with twenty-two other people with hard to manage Type 1 diabetes, had been waiting for the first of its kind cellular transplant study to begin at the University of Miami’s Diabetes Research Institute (DRI). All 23 candidates, who were selected from an international applicant pool of nearly 400, had been carrying global pagers in hopes that they’d be notified of a suitable organ match.
The sound of Jackie’s pager meant that she would be the first Type 1 diabetic patient in this country to be infused with clusters of insulin-producing cells, called islets, without also having to receive an organ transplant at the same time.
Until now, islets have only been available to patients who also required a life-saving organ transplant, such as a kidney or liver. These patients would have to take immune system suppressors for life in order to prevent their body from rejecting that organ. But these anti-rejection drugs pose many serious health risks, among them – cancer. In the case of organ transplants, these risks are considered acceptable since without the medication, the patient’s transplant would fail. But because diabetes is not immediately life threatening, as is liver or heart failure for example, the risk of taking these drugs for life far outweighs their potential benefit to a diabetic patient.
So patients with diabetes were only permitted to receive islets if they were already going to have to take anti-rejection drugs because of another, more life-threatening, system failure requiring organ transplantation.
The patients in this trial, however, will be the first to receive islets alone – without another transplanted organ – but with a new drug called anti IL-2 receptor antibody that will be given for only a short period of time along with other immune system suppressors. This antibody is the first genetically engineered drug that’s been shown to reduce the risk of rejection for transplanted organs.
“Before today, islet cell transplants that have worked in patients with Type 1 diabetes have required powerful immunosuppressors which included a cocktail of polyclonal antibodies – similar to shooting a spray of bullets at a target that you can not see well,” explains Camillo Ricordi, M.D., Stacy Joy Goodman professor of surgery and medicine at UM and Scientific Director of the Diabetes Research Institute.
“This approach results in a lot of generalized damage – like inflammation – in order to get at a relatively small target,” he continues. “The availability of this and other novel drugs means we now have target-specific bullets – “smart” bullets – that will look for a receptor we believe may be important in the rejection process – a receptor found on activated immune system cells called T-cells. This antibody in particular may let us block the early activation of the immune system without having to use a cocktail of antibodies, and give the transplanted islet cells a better window of opportunity to establish themselves in a new host.”
In addition, researchers will try to achieve a state of “donor specific tolerance” in this trial by giving patients bone marrow cells taken from the same donor as the islets. But these bone marrow cells will be unique, and a product of newly available technologies.
These bone marrow cells will have been “enriched” for a certain type of cell believed to facilitate the acceptance of the transplanted islets. “This newly developed technology enables us to efficiently select out a type of bone marrow cell called CD34+ stem cell,” explains Rodolfo Alejandro, M.D., professor of medicine at UM and Associate Director of the DRI’s Cell Transplant Center.
“That is another way of saying that we’re eliminating the more mature T cells from the donor’s marrow – the ones we believe may cause a reaction against the host’s cells called graft versus host disease.” If this new combination of islets/enriched bone marrow/anti IL-2 receptor proves successful, the recipient’s immune system will become “tolerant” to and accept the transplanted islet cells.
Then the other anti-rejection medications will be gradually tapered off at the end of a year as planned. DRI’s cell transplant team, currently conducting four simultaneous islet transplant trials, has plans to transplant twelve patients within the coming year under this newest protocol.