A recent clinical trial monitored by City of Hope’s Bart Roep, Ph.D.
, showed promising results for a possible cure of type 1 diabetes (T1D). Although the study involved risky stem cell transplant procedures, it identified new paths for personalized therapies of T1D.
The trial, which was conducted in Brazil, enrolled 21 T1D patients who had received autologous hematopoietic stem cell transplantation (AHSCT), which involves the use of a person’s own stem cells.
Participants were monitored and assessed every six months. Most patients became insulin free for an average of 3.5 years after transplantation. C-peptide levels — which show how much insulin is being made by the pancreas — remained higher than initial values for at least four years post-AHSCT, indicating temporary immunological balance and preservation of insulin-secreting beta cells. Loss of beta cells is what causes T1D and the symptoms associated with the disease.
“This means we can cure type 1 diabetes, be it with a risky therapy — although one that is also very successful in cancer, and one for which City of Hope is a world-renowned expert, with more than 14,000 patients having received similar treatment for blood cancers,” said Roep, the Chan Soon-Shiong Shapiro Distinguished Chair in Diabetes and professor and founding chair of the Department of Diabetes Immunology
He continued: “We now understand stem cell transplants can succeed in treating diabetes for some, but not in others, and we can predict either outcome before the therapy is administered by 'reading' the immune signature of the patient with a novel nanotechnology that I developed.”
The trial, the results of which were published in the Feb. 22 issue of the journal Frontiers in Immunology, showed that insulin independence is possible for T1D patients through the use of AHSCT because the transplanted stem cells are able to balance the immune system. The study also aimed to understand why some patients saw long-term clinical benefit from the transplantation while others did not.
“One patient is free of insulin for more than eight years now, without any major side effects,” said Roep, director of City of Hope’s Wanek Family Project to Cure Type 1 Diabetes
, which aims to find a cure for T1D in six years. But he also points out that some participants had little to no benefit. “However, we discovered the immune signature predicting these outcomes — either favorable or not — which is the first step toward personalized medicine in type 1 diabetes. We have a foot in the door.”
Because stem cell transplants involve severe immunosuppression prior to transplantation — meaning that the immune system is temporarily weakened — the procedure can be dangerous and will unlikely become the first line of defense for T1D.
However, the lessons learned from this and other trials will inform new paths for potential treatments. This trial’s findings will aid in the development of new strategies of AHSCT that could lead to even better outcomes for more patients, and will guide future research protocols on immunotherapies for T1D.
“This study paves the way for personalized therapy in type 1 diabetes,” said Roep. “Understanding why it sometimes fails will allow us to design new treatment strategies for those less fortunate patients. Also, it is the first definitive proof that T1D can be cured.”