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Discovery at Ceinge molecule against pediatric tumor cerebellum

Good news from Ceinge of Naples: «The pediatric tumor of the cerebellum, the medulloblastoma-group 3, can be defeated». This is confirmed by Massimo Zollo, Professor of Genetics at the University of Naples Federico II and Principal Investigator of Ceinge who coordinated the team of researchers who after years of work announce the interesting discovery. Researchers have unveiled how metastases are born and proliferate and have experienced in vivo a new drug that can not only stop its growth, but reverse the process from malignant to benign. For the moment the molecule has been tested on laboratory mice and has been fully effective and without contraindications. Now it will now have to undergo toxicity and pharmacodynamic studies in humans, so that it can be used for therapeutic purposes in children. An important goal for the diagnosis and treatment of a type of pediatric tumor for which up to now there was no effective therapy. Thus a new hope is born for the diagnosis and treatment of an evil that afflicts children. The success of the study was consecrated with the publication in the prestigious international scientific journal Brain (Oxford, Journal of Neurology).

A large part of the experiments, started by Pasquale de Antonellis, were performed by Veronica Ferrucci, a young SEMM graduate student, European School of Molecular Medicine based in Ceinge. The researcher has identified the mechanism of action of the metastatic process that starts from medullosfere, the cancer stem cells, present in the cerebellum and generates metastases in the spinal column of the affected child. This action has been replicated in murine models, which have undergone xenograft of the group 3 cells and it has been shown that it is possible to inhibit the proliferation and migration process of these cells in the cerebellum of the mice which are no longer able to activate the metastatic process thanks to the use of the new drug developed by the research group. Another datum present in the work shows that the combination of the radiation to metastatic cells of MB group 3 and the presence of the drug achieves a superior effect compared to the single use of the two therapeutic components and that is therefore applicable in the context of conventional therapy protocols for ‘high-risk’ cancers in the child. Moreover, thanks to the Next-Generation-Sequencing studies carried out in the Ceinge facility and coordinated by Francesco Salvatore and Valeria d’Argenio, the mutations occurring during tumor progression were identified with the sequencing of the entire genome of metastatic cells of the child affected by medulloblastoma of group 3.

«In this way other new target genes have been identified ̵

1; explains Massimo Zollo – whose mutations were unknown for human therapy. This study defines for the first time that tumors in the child’s cerebellum show mutated genes that negatively influence the action of the immune system active in the brain. So the immunotherapeutic approach that acts through a specific activation of the immune cells themselves to fight the tumor must be used with caution due to the presence of genetic mechanisms of escape from the action of the immune system in fighting Medulloblastoma “.Geneticists , chemists, biochemists, pharmacologists, structural biologists, surgeons, pathologists worked side by side to achieve this result. A work carried out at an international level with the contribution of researchers and doctors from Naples to London, passing through Dusseldorf, Paris and Uppsala, up to Toronto and San Francisco. The research team participated in the neurosurgery team of the Santobono Hospital, with Giuseppe Cinalli, Lucia Quaglietta and Antonio Verrico. Vittoria Donofrio, a doctor of the Santobono, took care of the pathological and clinical aspect together with Felice Giangaspero of the University La Sapienza of Rome and Angela Mastronuzzi of the Bambin Gesù Hospital in Rome. Molecular studies linked to the synthesis and definition through dynamic drug interaction studies with the Prune-1 protein were conducted by Aldo Galeone of the Pharmacy department of Federico II of Naples, and by Roberto Fattorusso of the L. Vanvitelli University of Naples .

The research was born from the encounter with Leonardo, a child affected by a type 3 medulloblastoma, which did not leave him alone. He was 5 years old when he was diagnosed. “One day he came here to Ceinge with his parents – says Zollo – his father had asked to find the best scholar of his illness. Leo was with us, he entered the laboratories, he met our researchers. He wanted us to explain what we do. His courage was not in vain “. In fact, the study of the Zollo group was done right on a sample of Leo. From that meeting Zollo and his people did not stop for a moment to study, to try, to verify. «It took so much tenacity, effort and determination to carry out this study and all the forces put in place, I speak of all the national and international collaborations that have had, have played an important role. And I do not deny that Leo was and is always in our hearts, our guide “. Leo left in October 2015. Nobody forgot that brave child, his smile, his strength. The school that he attended, together with his family, teachers and students, supports scientific research, which takes place in Naples, with a series of initiatives. «Just go to the Facebook page of Leonardo’s school, read what his classmates are doing, see all the love and solidarity that exists, to understand why we work relentlessly», said Massimo Zollo.

The team of researchers failed to save Leo, but his courage led the researchers to take a huge step forward in the quest to defeat one of the most aggressive tumors of the cerebellum in the child. Group 3 medulloblastoma is a typically metastatic tumor, affecting the cerebellum and IV ventricle, and gradually producing metastases in the spinal column. Diagnosis occurs by mediated magnetic resonance and it is not always possible to intervene surgically. About 50% of cases after about 2 years have a poor prognosis. “Now we are able to make a diagnosis of the medulloblastoma of group 3 – explains Zollo – which unfortunately have a poor prognosis. Now we finally have a weapon, a small molecule that can be used for clinical development. Unfortunately, to start this business for human studies we need investments, we are ready to welcome actions of pharmaceutical companies that want to invest in this development and take this molecule to become a drug. We are able to immediately switch to phase 1 studies, in Italy and abroad “.

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