UCSF Aims to Apply Precision Medicine Techniques to Diabetes

UC San Francisco (UCSF) is using a $1 million grant to build a first-of-its-kind diagnostic center that will aim to use precision medicine methods to find targeted therapies for type 1 diabetes.

The goal is to offer a central resource to families with type 1 diabetes and other heritable immunological conditions to receive personalized care and genetic counseling. The multi-disciplinary effort will work to better understand complex immunological disorders and advance translational research.

The onset of type 1 diabetes is attributed to a number of factors, including genetics and some viruses. About ten percent of type 1 diabetes patients have a family member with the condition. However, scientists have only recently had access to genome sequencing tools that can rapidly determine which errant gene might be driving the disease, and whether multiple gene variants or just one are involved.

A donation of $1 million recently created the Breakthrough Initiative in Type 1 Diabetes Precision Medicine and Discovery. The initiative will provide clinician-scientists with additional resources to help find candidate genes for different forms of type 1 diabetes, analyze them, create animal models in the laboratories, and then start thinking about targeted therapies.

“We’re calling it a breakthrough initiative because it’s really an engine that can fuel a lot of different early-stage research projects,” said immunologist Mark Anderson, PhD, UCSF’s Robert B. Friend and Michelle M. Friend Professor of Diabetes Research.

The research team has already started identifying several novel genes that by themselves can put someone at a very high risk of developing type 1 diabetes. The group is also encouraged by a recent case of an adolescent patient with type 1 diabetes at Texas Children’s Hospital in Houston, which is affiliated with Baylor College of Medicine. Due to a genetic finding and precision therapy, the patient no longer needs insulin to maintain blood sugar levels.

“Reversing diabetes is tough,” said endocrinologist Mike German, MD, associate director and clinical director of the UCSF Diabetes Center and the Justine K. Schreyer Professor in Diabetes Research.

“But in the Baylor case, it worked – possibly because the child had only had type 1 diabetes for a few years. If we can identify the particular pathways involved with type 1 diabetes and catch the disease at the right point, we may be able to prevent or reverse it.”

Knowing whether you or your family members might have a higher than normal risk for type 1 diabetes is important because opportunities may exist to target the biological pathways with precision therapies before diabetes takes hold and the body’s beta cells are destroyed.

“The sooner you have that information, the quicker you can do something about it,” said German.

However, finding the genes responsible for disease onset can be a challenging task, researchers noted.

“One of the ways we whittle down the pool is by looking through databases of the genes and seeing where they are expressed. If we find something that is expressed in the pancreas, that might be interesting to us,” said Zoe Quandt, MD, an endocrinologist and postdoctoral fellow in Anderson’s lab.

The team hopes that by answering the question of why a family has this disease, they can find new interventions that may be applicable to larger groups.

“This is precision or personalized medicine for diabetes,” said Steve Gitelman, MD, director of UCSF’s Pediatric Diabetes Program, and the Mary B. Olney,MD/KAK Distinguished Professor in Pediatric Diabetes and Clinical Research. “Once the mutation of a pathway is discovered, targeted therapies might be possible that either prevent or halt the disease.”

With the recent $1 million grant, the research team expects that the initiative will help pinpoint the genes that lead to the onset of type 1 diabetes.

“Resources provided by the new UCSF Precision Medicine and Discovery Fund will result in more patient stories like the one at Baylor College of Medicine,” Anderson said. “Ultimately, our research at UCSF will lead to greater opportunities for prevention, targeted treatments, and better outcomes for patients and their families. I am so grateful for the support we receive from donors that allows us to continue this exciting journey of discovery.”

Recently, researchers have sought to apply precision medicine techniques to gain a more comprehensive understanding of diabetes. NIH announced that it would fund a nationwide study involving 20 research centers to better understand unusual types of diabetes, which could accelerate precision medicine for the condition.

The Rare and Atypical Diabetes Network (RADIANT) will screen about 2,000 people with unknown or atypical types of diabetes that do not fit the forms of type 1 and type 2 diabetes.

“It’s extremely frustrating for people with atypical diabetes when their diabetes seems so different and difficult to manage,” said the study’s project scientist, Dr. Christine Lee of NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).

“Through RADIANT, we want to help patients and the broader healthcare community by finding and studying new types of diabetes to shed light on how and why diabetes can vary so greatly.”