Ketogenic metabolic therapy may act synergistically with IDH1 mutant glioblastoma

British men who refused standard treatment for brain tumors had a very slow growth of typically fatal glioblastoma tumors after adopting a ketogenic diet. Instead, a particularly aggressive cancer.

Recently published in the journal Nutrition frontier, This report is the first assessment of the use of ketogenic metabolic therapy (KMT) without chemotherapy or radiation therapy in patients diagnosed with IDH1 mutant glioblastoma (GBM). Ketogenic therapy is a non-toxic nutritional approach that is considered complementary or alternative, using a low-carbohydrate, high-fat diet to manage a variety of cancers, including glioblastoma.

In this particular case, the patient’s tumor contained a mutation known as IDH1. This mutation is known to be acquired by chance and improve overall survival.Therefore, the findings are particularly relevant to other patients whose tumors contain this mutation, a major co-author of the report and long advocating the benefits of KMT in the treatment of disease. According to researcher Thomas Sayfried, a professor of biology at Boston University.

GBM, like most malignancies, relies on fermentation for energy synthesis and survival, so by simultaneously limiting fermentable fuels such as glucose and glutamine and raising non-fermentable ketone bodies, It provides a non-toxic therapeutic strategy for managing GBM. Further research is needed to test this hypothesis in other patients diagnosed with GBM.“

Thomas Seyfried, co-author and principal investigator of the study, professor of biology at Boston University

Glioblastoma kills about 15,000 people each year, most of them unmanageable. Although standard treatment is shifting to new immunotherapy, the median GBM survival of 11 to 15 months has not improved significantly over 100 years, according to co-authors.

Many of the high-profile cases show the fatal developments of GBM. The late Senator John McCain was diagnosed with glioblastoma at the age of 80 in July 2017 and died in August 2018. Senator Edward M. Kennedy lived for a year after being diagnosed with GBM and was 77 years old. Bo Byden, son, was diagnosed with GBM at the age of 44 in August 2013 and died in May 2015.

Current standard treatments for GBM include surgical resection, radiation therapy, and chemotherapy, which have been shown to cause significant toxicity. However, it is difficult to initiate large-scale clinical trials of alternative therapies, and researchers need to carefully consider individual cases.

Patients in this case were diagnosed with glioblastoma in 2014 and avoided traditional standard treatments and instead avoided a self-directed ketogenic diet low in carbohydrates and high in fat to manage their cancer. I embarked on therapy.

Researchers found that “the patient’s tumor continued to grow very slowly for three years without the expected angiogenic edema until 2017,” said Seyfried and his co-author, the University of Pittsburgh. Researchers Purna Mukherjee, University Hospital Plymouth NHS Trust, UK and US-based nutritionist Miriam Calamian, Dr. Joseph Maroon of the University of Pittsburgh, Dr. Julio Zuccoli of the University of Pittsburgh School of Medicine

At that point, the patient underwent “surgical weight loss” of the tumor. Pathological specimens confirmed the diagnosis of GBM and confirmed that the patient’s tumor also contained the IDH1 mutation.

“After surgery, patients continued on a self-administered ketogenic diet and maintained low glucose-ketone index (GKI) levels, indicating therapeutic ketosis,” the researchers report. “In light of the continued slow progression of residual tumors, patients have incorporated mindfulness techniques to reduce stress and have enhanced KMT since October 2018. Magnetic resonance imaging (MRI) Although showing slow-paced tumor progression, the patient has a good quality of life at the time of this report. ”He is now 82 months from his first diagnosis.

“I was surprised to discover that KMT can work synergistically with IDH1 mutations to simultaneously target the two major metabolic pathways needed to promote GBM growth,” Seyfried said. Drives the glycolytic pathway and glutamine drives the glutaminolysis pathway. “

“Tumors containing GBM cannot survive without glucose and glutamine. In our study, acquired somatic mutations act synergistically with a low-carbohydrate, high-fat diet, resulting in a deadly brain. We have identified a new mechanism that provides long-term management. Tumors. “

There is a great deal of interest in these individual case studies, but the co-authors said: “It is not possible to predict whether the therapeutic effect on KMT seen in our GBM patients will be seen in other GBM patients treated similarly. We acquired a spontaneous IDH1 mutation in the tumor. If you need a glutamine-targeted drug that is used with KMT to control tumor growth. “

According to additional studies they conducted, researchers used KMT and a pan-glutaminase inhibitor (known as 6-diazo-5-oxo-L-norleucin (DON)) to make glucose and glutamine available. It was noted that simultaneous targeting of the mice was shown to be possible, significantly prolonging the survival of preclinical syngeneic glioblastoma in mice. Previous studies have shown that the ketogenic diet facilitates the delivery of small-molecule therapeutics across the blood-brain barrier without toxicity.