Infants with insulin disorder spared pancreatic surgery thanks to new drug therapy
HOUSTON – (April 1, 2014) – A new drug treatment based on research at The University of Texas Health Science Center at Houston (UTHealth) prevented four children with a rare insulin disorder from losing their pancreas. They were treated at Great Ormond Street Hospital in London.
The patients, who all have a severe condition that produces excess insulin, are doing well a year after starting the medical treatment called sirolimus, reports a study in The New England Journal of Medicine. The condition is called hyperinsulinemic hypoglycemia (HH) and severe HH can lead to brain damage and other complications.
In a worst case scenario, surgeons must remove most of the pancreas to eliminate the source of insulin. However, surgery is not a cure and some patients can continue to experience HH symptoms and develop diabetes. The pancreas produces the insulin that regulates blood sugar levels.
Drugs such as diazoxide and octreotide are normally used to stabilize blood sugar levels, but the standard medication does not work for the severest forms of HH.
“The therapy for this condition has been historically frustrating since there are not many available medications that can be used for a long time,” said Michael Yafi, M.D., assistant professor and director of the Division of Pediatric Endocrinology at the UTHealth Medical School, as well as a member of the medical staff of Children’s Memorial Hermann Hospital.
“The study’s authors have used a new medication to treat this condition with great results in maintaining euglycemia one year post therapy. Time will prove if such medication will be able to save all neonates with such a condition from the need of pancreatectomy,” he added.
The UTHealth research was led by two professors in the Department of Pathology and Laboratory Medicine at the UTHealth Medical School – Robert E. Brown, M.D., and Nina Tatevian, M.D., Ph.D. Sanda Alexandrescu, M.D., a former pathology resident, also contributed to the research. All are study authors.
This new drug treatment is based on a 2010 case study of HH in newborns by Brown, Tatevian and Alexandrescu in which they found that the mTORC1 pathway was overexpressed in the pancreas and suggested sirolimus as a therapy.
Senthil Senniappan, M.D., lead author and clinical research fellow at Great Ormond Street Hospital, acted on this insight and four patients at the London hospital who had not responded to diazoxide and octreotide and whose remaining option was to have their pancreas removed were offered sirolimus as an alternative treatment.
All four patients responded well to sirolimus treatment and were discharged home safely without the need to remove their pancreas. Senniappan said, “One year on, all the patients are doing well with stable blood glucose levels and no significant side effects.”
Khalid Hussain, M.D., senior author and consultant in endocrinology at Great Ormond Street Hospital, said, “Identifying the key pathways involved in hyperinsulinemic hypoglycemia has helped us to find the most suitable treatment for these patients. We hope that in the long-term, the treatment will lessen the severity of the condition, enabling patients to be moved onto more standard drugs such as diazoxide. This new discovery could change the way patients with the disease are managed in the future.”
Recently, Senniappan visited Brown and Tatevian in Houston to learn more about morphoproteomic methods and consultative proteomics, a specialty consultative service that suggests treatment options based on expert interpretation of molecular pathway networks, particularly in hard-to-treat or recurring cancers.
Subsequently, Senniappan and Hussain have uncovered new genomic findings related to the mTOR pathway in such patients and are actively collaborating with Brown and Tatevian in providing correlative studies using morphoproteomics.
Brown said the hope is that the findings can be applied to the discovery of adjunctive therapies that will work with sirolimus in avoiding pancreatic surgery and in reducing the risk of side effects in these infants. Brown is the Harvey S. Rosenberg, MD Chair in Pathology and Laboratory Medicine at UTHealth.
Brown and Tatevian serve in the Department of Anatomic Pathology at Memorial Hermann-Texas Medical Center.
This article includes information from a press report issued by the Great Ormond Street Hospital.
Information on the UTHealth Consultative Proteomics service is available by calling or visiting https://med.uth.edu/pathology/clinical-services/consultative-proteomics/
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