Type 1 diabetes is an autoimmune disease in which the body’s immune system attacks and destroys insulin-producing beta cells in the pancreas. Traditional management of his type 1 diabetes has primarily relied on replacing the missing insulin with injections, which, while effective, can be expensive and burdensome.a new research A team of researchers from the University of Chicago Medicine and Indiana University suggests that existing drugs could be repurposed to treat type 1 diabetes, potentially reducing reliance on insulin as the only treatment.
The study focuses on a drug known as alpha-difluoromethylornithine (DFMO), which inhibits an enzyme that plays a key role in cellular metabolism. The latest translational results are the culmination of many years of research. In 2010, while corresponding author Raghu Mirmila, MD, was a student at Indiana University, he and his lab performed basic biochemical experiments on beta cells in culture. They found that suppressing altered metabolic pathways by DFMO helps protect beta cells from environmental factors, preserving and even improving recovery of these vital cells in patients diagnosed with type 1 diabetes. suggested the possibility of doing so.
After confirming their observations preclinically in zebrafish and then in mice, the researchers found that lead author Linda Dimeglio, MD, MPH, Edwin Retzter Professor of Pediatrics at Indiana University School of Medicine and Pediatrician at Riley Children’s Health, Endocrinologists have started a clinical trial to evaluate safety. Tolerability of drugs in patients with type 1 diabetes. The results of this trial using DMFO, funded by the Juvenile Diabetes Research Foundation (JDRF) and provided by Panvera Therapeutics, show that the drug is safe for people with type 1 diabetes and protects beta cells. showed that it may help keep insulin levels stable.
“What we as physicians and scientists have always strived for is to discover something at a very basic, fundamental level in the cell and find a way to bring it into the clinic,” Milmira said. he said. Endocrinologist and professor at the University of Chicago School of Medicine. “This clearly demonstrates the importance of supporting basic science research.”
“After this long journey, we are thrilled to see the promising results in our pilot studies and are excited to continue our fruitful collaboration in the future,” said Dimeglio.
Importantly, DFMO has already received FDA approval as a high-dose injectable for the treatment of African sleeping sickness since 1990, and in 2020 received breakthrough therapy designation as post-remission neuroblastoma maintenance therapy. This means that they are receiving Existing regulatory approvals may facilitate use in type 1 diabetes. Save effort and money and get treatment to patients faster.
“For drugs already approved for other indications, approval timelines can take years rather than decades, once solid clinical evidence of safety and efficacy is obtained.” Mirmira said. “Using the new formulation of DFMO as a tablet allows patients to take it orally instead of regular injections, with a very favorable side effect profile. It works differently than other treatments for this disease. I am very happy to be able to say that I have developed a drug that does this.”
To follow up on recently published results, first and co-corresponding author Emily K. Sims, MD, associate professor of pediatrics at IU School of Medicine and pediatric endocrinologist at Riley Children’s Health, conducted a multi-institutional We have initiated and provided funding for joint clinical trials. To gather even stronger data on the effectiveness of her DFMO as a treatment for type 1 diabetes, JDRF collaborated with UChicago among its trial sites.
“Our promising initial findings show that DFMO, perhaps as part of a combination therapy, may offer a potential benefit in preserving insulin secretion in patients with recent onset type 1 diabetes, who are ultimately at risk for type 1 diabetes. “We’re hopeful that people may be tested as well. They have ongoing symptoms,” Sims said.
“We are beginning a new era of thinking about new ways to modify the disease using different types of drugs and targets not traditionally considered in type 1 diabetes treatment,” Mirmira said.
The study, “Inhibition of polyamine biosynthesis maintains β-cell function in type 1 diabetes,” Cell medicine report Co-authors include Emily K. Sims, Abhishek Kulkarni, Audrey Hull, Stephanie E. Werner, Suzanne Cabrera, Lucy D. Mastranrea, Batur Hammoud, Soumyadeep Sarkar, and Ernest S. Nakayas. , Teresa L. Mastruck, and Susan M. Perkins, Ouyang Fangqian, Bobbie-Joe Webb-Robertson, Jacob R. Enriquez, Sarah A. Turcy, Carmela Evans-Molina, S. Alice Long, Lori Blanchfield, Eugene W. Garner. , Raghavendra Mirmila, Linda A. Dimelio.