Accelerating Transformational Research into Cell Transplantation for Patients with Type 1 Diabetes

A personal investigation into the lifelong implications of his type 1 diabetes (T1D) culminated in a $7 million gift from Mike Gordon, co-founder of Meritech Capital Partners, and his wife, Loren, to help UCSF surmount a key impediment to treating the disease. The funds will support world-class stem cell biologists, immunologists, and bioengineers who are working to overcome significant barriers to beta-cell replacement therapy as an effective treatment for T1D.

Diagnosed when he was just 22 months old, Gordon went through a whole pancreas transplant at UCSF nearly 12 years ago. As a result, he has fewer complications from T1D but must take immunosuppressant drugs – and endure the health risks that come with them – for the rest of his life.

We wanted to give these researchers freedom to explore bold ideas.

“I’ve suffered a lot from this disease,” Gordon said. “People say, ‘It’s not that bad. It’s a chronic condition.’ But you can fall apart.”

Some 1.6 million people in the US have T1D, a disease that is often disabling and can become life-threatening. Diagnoses typically occur in childhood, but not always. The disease develops when the patient’s immune system attacks its own beta cells, which make insulin in the pancreas. The resulting lack of insulin leaves the body unable to absorb sugar from the bloodstream and convert it into energy, so sugar builds up in the blood. Patients are subject to a lifelong dependence on insulin and are at a higher risk for heart disease, blindness, kidney failure, and other chronic conditions, in addition to shortened average life expectancy.

Beta cell-replacement therapy has shown enormous promise for T1D patients. Beta cells make up 50%-70% of the cells in human pancreatic islets – groups of cells in the pancreas that produce blood glucose-regulating hormones – and they are the sole producers of insulin in the body. However, replacement beta cells don’t live long, and the immune system often rejects the ones that do survive. To prevent the immune system from attacking the replacement cells, immunosuppressants are necessary, but they can be toxic and leave patients vulnerable to malignancies and other infections. UCSF scientists are poised to find solutions to these challenges.

“So often the NIH provides funds for low-risk projects where outcomes are more predictable,” Gordon said. “We didn’t want that; we wanted to give these researchers freedom to explore bold ideas.”

The research team will use the Gordons’ investment to help answer two big questions: How can they prolong the survival of replacement beta cells after transplantation? And, can the need for patients to take immunosuppressive drugs be eliminated? The answers to these questions will be a game-changer for patients around the world.

Connecting Brilliant Minds

Four interdisciplinary investigators will lead the research:

Audrey Parent, PhD
Adjunct assistant professor in the UCSF Diabetes Center

Qizhi Tang, PhD
Professor in the UCSF Diabetes Center, the UCSF Division of Transplantation, the UCSF-Gladstone Institute of Genomic Immunology, and the UCSF Broad Center of Regeneration Medicine and Stem Cell Research

Julie B. Sneddon, PhD
Assistant professor in the UCSF Diabetes Center, the UCSF Broad Center of Regeneration Medicine and Stem Cell Research, and the UCSF Department of Cell and Tissue Biology

Tejal Desai, PhD
Professor of Bioengineering and Therapeutic Sciences and director of UCSF Health Innovation Via Engineering (HIVE) Program

Currently, islet-cell replacement relies on obtaining pancreatic tissue from deceased human donors. Thanks to groundbreaking advances during the last decade, beta cells can now be laboratory-generated from pluripotent stem cells, which means supplies, in theory, are unlimited. This creates an opportunity to engineer the stem cell-derived beta cells in ways that support their survival and help them avoid attack by the immune system.

“We used to say we were 10 years away from a cure for T1D. We still might be. But if you look at the advances in cell biology and immunology, we have the road map now,” Parent said.

Over the past five years, Drs. Parent, Tang, Sneddon, and Desai have co-advised trainees, joined forces on numerous projects, and published papers together. Their labs combine the fresh perspectives and innovation of junior faculty members with the expertise and experience of senior faculty members. The group’s collective knowledge, unique understanding, and productive ongoing collaborations position them as an effective group to take on this challenge.

Heralding a New Era in Diabetes Research

Insulin was first used to successfully treat a patient with type 1 diabetes a century ago, but it wasn’t until 1980 that two Minnesota surgeons demonstrated successful intraportal islet transplantation in 10 patients with surgically induced diabetes (in which the patients’ own islet cells, or autografts, were infused back into their bodies after islet isolation). Ultimately, three of those patients achieved insulin independence for one, nine, and 38 months, respectively. In the last decade, significant strides have been made in groundbreaking technologies such as immunotherapy, metabolomics, and genomics. UCSF has been at the forefront of these advances, especially in immunology, with the Bakar ImmunoX initiative driving collaborative science and the UCSF Helen Diller Family Comprehensive Cancer Center using immunotherapies to find cures for some cancer patients.

All this progress has positively impacted diabetes research. Mark Anderson, MD, PhD, the Robert B. Friend and Michelle M. Friend Professor of Diabetes Research and the new director of the UCSF Diabetes Center, is optimistic about this moment in time and what it means for our patients with T1D and other diseases.

“These developments provide unique opportunities for physician-scientists to research the molecular causes of diseases like T1D and potentially replace damaged tissues and repair malfunctioning organs,” Anderson said.

Anderson believes that UCSF is one of the few places in the world capable of assembling this type of collaborative team. “We are so fortunate to have the Gordons’ support and shared vision to help us realize the potential of cell transplantation without immune suppression, which could completely change the lives of those affected by T1D.”