Precision Medicine Approach Reverses Case of Type 1 Diabetes

A precision medicine treatment that involves correcting an underlying genetic mutation led to the reversal of a case of type 1 diabetes, according to a study published in the New England Journal of Medicine.

Until now, treatment options for type 1 diabetes have consisted of managing blood sugar levels with insulin and diet and exercise to prevent any further complications.

The study focused on a male patient who was diagnosed with classical autoimmune presentation of type 1 diabetes at 17. The patient also suffered from recurrent respiratory infections. Researchers took a deeper examination of the patient’s genome and found that he harbored a harmful mutation in the gene STAT1 (signal transducer and activator of transcription 1).

The mutation boosted the activity of the STAT1 protein. Enhanced STAT1 protein activity is known to drive respiratory infections and various autoimmune conditions, including type 1 diabetes.

Providers treated the patient with ruxolitinib, a potent inhibitor of the JAK/STAT signaling pathway, which has previously been shown to improve many symptoms related to enhanced JAK/STAT signaling.

A year after the start of the ruxolitinib therapy, and close to two years after his type 1 diabetes diagnosis, the patient was able to discontinue daily injections of insulin and still maintain normal blood glucose levels.

“To the best of our knowledge, this is the first example of a T1D patient who has experienced a complete reversal of insulin dependence,” said corresponding author Dr. Lisa R. Forbes, deputy director for clinical services and community outreach for the Texas Children’s William T. Shearer Center for Human Immunobiology and assistant professor of pediatrics, immunology, allergy, and retrovirology at Baylor.

“We are excited by the prospect that this approach could be a viable therapeutic strategy for a subset of T1D patients.”

The results demonstrate the potential for precision medicine therapies to reverse chronic conditions like diabetes.

“This case was quite fascinating,” said one of the lead authors, Dr. Sophia Ebenezer, assistant professor of pediatric endocrinology at Baylor and Texas Children’s. “The patient no longer needs daily insulin injections and has shown full remission of other clinical signs of T1D along with marked improvements in his quality of life.”

Although the results are promising, researchers noted that this could be a transient effect and the condition could recur later in the patient’s life. Researchers will need to do a longer clinical assessment of the patient to ensure that he can stay insulin-free permanently.

“We are encouraged by the amazing outcome of using a targeted approach to control T1D in this patient. We think these positive results warrant further careful evaluation on how the reversal occurred,” said Dr. Mark Anderson, professor and Michelle M. Friend Endowed Chair in Diabetes Research at the University of California, San Francisco Diabetes Center and one of the study’s lead authors.

“The results also raise the possibility that immune-modulating drugs like ruxolitinib should be given careful consideration for use in future clinical trials for reversing T1D.”

Precision medicine approaches are increasingly demonstrating their ability to reverse common chronic conditions.

In a study recently published in EMBO Molecular Medicine, researchers used a precision medicine therapy to target a genetic mutation causing severe lymphatic disorder in a patient.

The results showed that the approach eventually resolved the disorder, enabling the patient to breathe normally and exercise again.

“The resolution of lung disease with lymphatic remodeling is remarkable and potentially should change how we evaluate and treat lung disease in this patient population,” said first author Jessica B. Foster, MD, an attending physician in Children’s Hospital of Philadelphia's Division of Oncology.

“These results offer hope to other patients with lymphatic-induced lung disease and warrant further investigation.”