Type 1 Diabetes: A Treatment’s In Sight?

A Leader in Immunogenetics

McGowan Institute for Regenerative Medicine faculty member Massimo Trucco, MD, is an international leader in the field of immunogenetics, having dedicated his life’s work to finding a cure for diabetes. Dr. Trucco is the Director of the Division of Immunogenetics at the Children’s Hospital of Pittsburgh of the University of Pittsburgh Medical Center, the Hillman Professor of Pediatric Immunology at Children’s Hospital, and a Professor of Pediatrics at the University of Pittsburgh School of Medicine.
Dr. Trucco was born in Savona, Italy. During his medical residency at Regina Marghertia Children’s Hospital, University of Torino, School of Medicine, he worked on research in tissue compatibility, an area directly related to bone marrow transplantation. His curiosity has driven him to move to three countries to study at renowned universities and research institutes, and work side-by-side with two Nobel Prize winners.

An established scientist, Dr. Trucco came to Pittsburgh in 1986 to focus his genetic and immunologic research on several significant diseases of childhood, including diabetes. Since then, his discoveries have led to:

• a better process for molecular typing for matching bone marrow donors and recipients;
• the ability to identify those at risk for diabetes;
• an understanding of the link between a virus and Type 1 diabetes;
• a potential cure for the pancreatic damage that causes insulin dependence.

Dr. Trucco and his team are closing in on a cure for Type 1 diabetes. He has made several significant findings including the isolation of a super-antigen that is believed to trigger juvenile diabetes in children. It is widely suspected that this discovery, and others that Dr. Trucco has made, will lead to a cure.

A Career Dedicated to Diabetes Research
Type 1 diabetes is regarded as an autoimmune disease because a person’s immune system’s T-cells attack and destroy the beta cells in the pancreas that produce insulin. Type 1 diabetes also is known as insulin-dependent diabetes mellitus or juvenile-onset diabetes. The Centers for Disease Control and Prevention (CDC) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)-funded SEARCH for Diabetes in Youth Study reports that 1 of every 523 youth had physician diagnosed diabetes in 2001 (this number included both Type 1 and Type 2 diabetes). SEARCH also found that about 15,000 youth are diagnosed with Type 1 diabetes each year.

Building on his 1994 discovery that Type 1 diabetes susceptibility may be genetic in nature and triggered by viruses, Dr. Trucco’s discoveries have continued to lead to better processes for molecular typing for matching bone marrow donors and recipients, the ability to identify those at risk for diabetes, an understanding of the link between a common virus and Type 1 diabetes, and a potential cure for the pancreatic damage that causes insulin dependence. The research milestones of Dr. Trucco include:

In 1977-78, research into why some organ transplants were successful and why some were not, as well as why all donors and recipients were not compatible, showed that abnormalities in HLA cells (histocompatibility locus antigens) were a genetic predisposition for autoimmune disease.
In 1988-90, landmark studies were published on the genetic susceptibility of certain individuals to Type 1 diabetes. Research also showed that the low incidence of diabetes in China is related to that population’s relative genetic resistance to the disease, while the high incidence of diabetes in Finland is related to that population’s genetic predisposition.
In 1998, the Coxsackievirus B is identified as one of the viruses responsible for triggering Type 1 diabetes, making it possible to potentially develop a vaccine.
In 2006, Dr. Trucco’s lab discovered a process using a patient’s own blood, combined with a safe mixture of molecules. With the use of this combination, it is possible to interrupt T-cell and beta cell interaction, which is known to cause diabetes. The team removed dendritic cells from the patient’s own blood, and the cells were mixed with the proteins CD40, CD80, and CD86, and injected back into the patient where it was found that the CD40, 80, and 86 block the process of the T-cell and beta cell interaction.

Dr. Trucco and his team continue their landmark research into improving the prediction of Type 1 diabetes and understanding and managing its complications. “We have some of the best researchers and clinicians in their fields, and it is conceivable that with this concentration of talent, Pittsburgh could be the place where the cure for diabetes is discovered,” says Dr. Trucco.

Recently reported by the Pittsburgh Post-Gazette, today Dr. Trucco needs $7 million to $10 million for a multi-site trial involving 105 people with a recent diagnosis of Type 1 diabetes. He’s considering beginning with 18-year-olds, and if the therapy succeeds, working backward in age to adolescents.

“It would be the first trial in which live cells are used to treat a disease that is not cancer, and we would be dealing with children,” Dr. Trucco said, discussing his desire to see results after decades of research.
A study published in Diabetes describes the advantages in using one’s own genetically engineered dendritic cells to stop the autoimmune cycle that destroys insulin-producing beta cells.

“It is our conviction that the age of personalized cell therapy … has arrived and that Type 1 diabetes could be the first autoimmune disorder to be successfully treated,” the study states.

Dr. Trucco is leading the pack of researchers targeting dendritic cells as the focus of treatment for Type 1 diabetes. The Phase I human clinical trial already has proven the therapy to be safe while raising excitement for success.

“Massimo clearly is the leader in the field, and the only one, to my knowledge, to get approval for a Phase I trial. He has the correct equipment and facilities to do this,” said C. Garrison Fathman, chief of the division of immunology and rheumatology at the Stanford University School of Medicine.

For proposed treatments, he’s leading the research in using adoptive cellular therapy, or modifying the immune system’s effect on certain cells, to treat a disease other than cancer.

The McGowan Institute congratulates Dr. Trucco on all his scientific achievements and thanks are extended to him and his colleagues on behalf of all of the patients that these emerging technologies may one day help.