Understanding epilepsy in pediatric tumors

Pediatric brain tumors are characterized by frequent complications due to intractable epilepsy compared to adult brain tumors. However, the genetic cause of refractory epilepsy in pediatric brain tumors has not been elucidated yet, and it is difficult to treat patients because the tumors do not respond to existing antiepileptic drugs and debilitate children's development.

A Korean research team led by Professor Jeong Ho Lee, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST) has recently identified a neuronal BRAF somatic mutation that causes intrinsic epileptogenicity in pediatric brain tumors.

Preoperative and postoperative brain MRI (left panel), tumor H&E (right upper panel) and GFAP immunohistochemical (right lower panel) staining images from a patient with ganglioglioma (GG231) carrying the BRAFV600E mutation. The white arrow and the black arrowhead indicate the brain tumor and a dysplastic neuron, respectively.

Credit: KAIST

The research team studied patients' tissue diagnosed with ganglioglioma (GG), one of the main causes of tumor-associated intractable epilepsy, and found that the BRAF V600E somatic mutation is involved in the development of neural stem cells by using deep DNA sequencing. This mutation was carried out in an animal model to reproduce the pathology of GG and to observe seizures to establish an animal model for the treatment of epileptic seizures caused by pediatric brain tumors.

Using immunohistochemical and transcriptome analysis, they realized that the BRAF V600E mutation that arose in early progenitor cells during embryonic brain formation led to the acquisition of intrinsic epileptogenic properties in neuronal lineage cells, whereas tumorigenic properties were attributed to a high proliferation of glial lineage cells exhibiting the mutation. Notably, researchers found that seizures in mice were significantly alleviated by intraventricular infusion of the BRAF V600E inhibitor, Vemurafenib, a clinical anticancer drug.

The authors said, "Our study offers the first direct evidence that the BRAF somatic mutation arising from neural stem cells plays a key role in epileptogenesisin the brain tumor. This study also showed a new therapeutic target for tumor-associated epileptic disorders."

In collaboration with the KAIST startup company, SoVarGen, the research team is currently developing innovative therapeutics for epileptic seizures derived from pediatric brain tumors. This study was supported by the Suh Kyungbae Foundation (SUHF) and the Citizens United for Research in Epilepsy.

 

We encourage researchers all around the globe to submit abstract on their latest research at our upcoming conference Cell Tissue Science 2019 which is mainly focuses on the complications the consequences of Stem Cell, Regenerative Medicine, Stem Cell Therapy, Cancer Cell Biology , Technical Advancements in cancer treatment   and many more.We welcome you to the our upcoming conference “ 12th World Congress on Cell & Tissue Science” . For more info visit :Cell Tissue Science 2019

Anti-cancer drugs may hold key to overcoming antimalarial drug resistance

Scientists have found a way to boost the efficacy of the world's most powerful antimalarial drug with the help of chemotherapy medicines. Scientists from the University of Melbourne and the Japanese pharmaceutical company Takeda have discovered that antimalarial drug artemisinin works through a "double whammy" attack on the deadly parasite.

The drug damages proteins in malaria parasites and clogs the parasite's waste disposal system, known as the proteasome.

Researcher Leann Tilley, University of Melbourne said: "The double whammy effect means that combining artemisinin with an anti-cancer drug that also targets the proteasome, complements the activity of artemisinin, and can restore activity against artemisinin-resistant parasites."

 

"The parasite's proteasome is like a shredder that chews up damaged or used-up proteins," Professor Tilley said. "Treating malaria parasites with artemisinin generates a lot of damaged proteins. Artemisinin and proteasome inhibitors thus can work together to jam the recycling system."

Blockage of the proteasome causes an accumulation of proteins that are marked with a "kiss of death" modification. When these damaged proteins build up, they stress the parasite and soon lead to cell death.

The team are working to identify parasite-specific proteasome inhibitors that could be advanced to clinical trials.

"At Takeda, we are proud to contribute our expertise to help address critical global health problems. In this case, we were able to leverage our oncology research on the proteasome system and uncover a potential new way to treat malaria," said Larry Dick, Director, Biochemistry, Oncology at Takeda.

 

"We are currently undertaking medicinal chemistry work to create novel analogs of human proteasome inhibitors that specifically inhibit the parasite proteasome " Professor Tilley said. "We want a compound that can be administered orally and will last a long time in the bloodstream. If a suitable compound can be found, human trials could happen very soon."

We welcome researchers from different part of the to submit abstract on their latest research at our upcoming conference Cell Tissue Science 2019 which is mainly focuses on the complications the consequences of Stem Cell, Regenerative Medicine, Stem Cell Therapy, Cancer Cell Biology , Technical Advancements in cancer treatment and many more.We welcome you to the our upcoming conference “ 12th World Congress on Cell & Tissue Science” . For more info visit :Cell Tissue Science 2019