Center for Diffuse Intrinsic Pontine Glioma (DIPG) & Diffuse Midline Glioma (DMG)

The DIPG/DMG Center Zurich is focusing on developing and implementing improved therapies for children diagnosed with DIPG/DMGs. 

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Mission and Vision

 

The DIPG/DMG Center Zurich is focusing on developing and implementing improved therapies for children diagnosed with DIPG/DMGs. The Program consists of a clinical and a translational research entity which reside within the Division of Oncology, University Children’s Hospital of Zurich, a non-profit hospital supported by the Eleonore Foundation. The DIPG/DMG Center in Zurich is a joint effort with the University of San Francisco, California (UCSF) allowing patients to receive the most up to date information.

Our mission is to develop and establish improved therapeutic measures to reach prolongation of the overall survival times.

 

About the Problem

 

It is recognized worldwide that over 1000 children die every year following being diagnosed with a specific brain cancer called Diffuse Intrinsic Pontine Glioma (DIPG)/Diffuse Midline Glioma (DMG). These tumors arise in the midline structures of the brain such as the thalamus, pons as well as spinal cord.

Over the last 50 years, clinical trials have not resulted in improved outcome for children diagnosed with DMGs. Radiotherapy -the only standard of care- often results in a transient tumor response but does not significantly impact the long-term outcome. The mean overall survival for diagnosed children with DMGs is about 9-12 months. However, in recent years, due to analyses of postmortem DIPG tumor specimens as well more and more upfront tissue sampling, our understanding of the biology of these tumors has significantly improved and it is now clear that DMGs including DIPGs are a heterogeneous group of tumors requiring a personalized therapy approach. Given the heterogeneity on a molecular level of these tumors, a “One size fits all” approach will not improve the outcome for these children.

 

From Bench to Bedside

 

Within our research center we evaluate and investigate new therapeutic options that can be transferred to the clinic.
We are focusing on the following topics:

  • Overcoming the blood brain barrier
  • Drug screening with patient derived tumor cells
  • Establishment of new predictive and scalable pre-clinical models
  • Biomarker analysis
  • Novel drug and drug combination discovery

 

 

 

Who we are

 

DIPG/DMG Center lead

  • Sabine Mueller, MD Ph.D. MAS serves as the Head of the Clinical Program of the DIPG/DMG . She also leads the Pediatric Brain Tumor Program at UCSF and the Pacific Pediatric Neuro-Oncology Consortium (www.pnoc.us)
  • Javad Nazarian, Prof. Ph.D. serves as the Head of the Translational Program of the DIPG/DMG Center Zurich

 

Clinical team

  • Dr. Stephanie Mathes, contributes to the DIPG/DMG Center Zurich at as project manager. Her main focus is to obtain regulatory approval for clinical trial opening and management of the program.
  • Dr. Nicolas Gerber is a pediatric neuro-oncologist and head of the Early Phase Clinical Trials Unit of the Department of Pediatric Oncology at the University Children’s Hospital of Zürich. He is PI of PNOC trials.
  • Prof Dr. Ana Guerreiro Stücklin, PhD is a pediatric neuro-oncologist and physician scientist at the University Children’s Hospital in Zurich, and will act as Co-PI for PNOC trials.
  • Dr. med. Annette Weiser, Clinical and Research Fellow Neurooncology/Oncology.
  • Marion Rizo-Oberholzer is study nurse at the DIPG/DMG Center Zurich and takes care of our patients and families.
  • Sabine Holzapfel is study nurse at the DIPG/DMG Center Zurich and takes care of our patients and families.
  • Prof. Dr. Michael Grotzer is the Full Professor of Pediatrics at the Medical Faculty of the University of Zurich and the Director of the Medical Clinic as well as the Medical Director at the University Children’s Hospital Zurich. Professor Grotzer is the head of Neuro Oncology where the center is embedded.
  • Prof. Dr. Niklaus Krayenbühl is the Head of Pediatric Neurosurgery at University Children’s Hospital of Zürich and Senior Neurosurgeon at the Department of Neurosurgery, University Hospital of Zürich.

 

Translational team

  • Sandra Laternser, MSc in Life Sciences is a research associate in Dr. Nazarian’s lab. She is working at the interface of clinic and research lab and investigating biomarkers of target drugs.
  • Bettina Kritzer, MSc in Life Sciences, is a research associate in Dr. Nazarian’s lab. She is working at the interface of clinic and research with a focus on cell characterization, drug screening and investigation on new treatment opportunities for DIPG patients.
  • Antonela Petrović, PhD in Medicinal Chemistry with research background in Molecular Neurobiology. She is working on new combinatorial therapeutic approaches in DMGs with a research focus on targeting the PI3K pathway.
  • Kamil Wojnicki, PhD in Molecular Biology. He is working on new therapeutic approaches in DMGs focusing on combinatorial strategies and PI3K/AKT pathway.
  • David Bamert, MSc in Biomedicine is a research technician in Dr. Nazarian’s lab. He is working at the interface of clinic and research lab and investigates emerging technologies to find new treatment possibilities.
  • Ludovica Ciani is a PhD student in Javad Nazarian’s Lab. She is working on identifying new therapeutic targets involved in DMG tumorigenesis and dictating cell stemness.
  • Matteo Bimbati is a PhD student in Javad Nazarian’s Lab. He uses the novel CRISPR-Cas9 technology approach to elucidate the molecular mechanisms underlying DMG survival and identify new therapeutic targets.

 

 

What we offer to patients and their families

 

We offer a detailed review of the medical history and images by an international team of experts specialized in the care of DIPG/DMGs. This will allow us to provide you with the best current treatment recommendations for your child. We will then schedule a video consultation with you and your family to discuss our recommendations. This could include:

  • Biopsy or further resection of the tumors
  • Drug screen on patient tumor cells for precision medicine
  • Participation in a clinical trial
  • Genomic analyses of the tumor tissue

Second opinions:

We are offering second opinions after detailed review of medical records, existing molecular data and images. Each patient will be discussed in the trans-Atlantic DIPG/DMG dedicated tumorboard with experts of the University Children’s Hospital Zurich and UCSF. This procedure allows to provide a recommendation for further steps in the medical care based on a broad expert opinion. We can offer second opinions either through in person visits or via telemedicine (video conferencing) in English, French or German, but when needed, we will be happy to set up a phone call with an interpreter.

Biopsies for molecular analysis of the tumor:

We perform surgical biopsies of these diffuse midline gliomas / diffuse intrinsic pontine gliomas routinely at the DIPG/DMG Center Zurich. The biopsy is performed using a robot-assisted platform. This will only require a short term stay for the child in the hospital. On the tumor tissue, we perform molecular profiling to get a deeper understanding of the tumor subtype and if feasible real-time drug testing. Results of these evolving tests will be used to develop a personalized therapy approach whenever feasible.

Drug Screen for precision medicine:

Each tumor, like each individual, is unique in its molecular profile. While there are some characteristic patterns in diffuse midline glioma and diffuse intrinsic brainstem glioma, ultimately small differences in cell signaling pathways can make a big difference in terms of drug efficacy. To help us choose the most promising therapeutic approach for your child in the clinic , we can pre-test how tumor cells respond to different drugs in our research laboratory. This process can help to select drugs which fit more precisely to the individual profile.

Clinical trials:

At the DIPG/DMG Center Zurich we are actively working on developing and implementing effective and novel clinical trials for patients diagnosed with DIPG and DMG. We are offering clinical trial enrollment but also work with several companies for compassionate use strategies if trial enrollment is not an option.

We are member of the Pacific Pediatric Neuro-Oncology Consortium. Please see all PNOC open trials here: www.pnoc.us

At the DIPG/DMG Center in Zurich we offer enrollment into the following trials.

  • PNOC022: A Combination Therapy Trial using an Adaptive Platform Design for Children and Young Adults with Diffuse Midline Gliomas (DMGs) including Diffuse Intrinsic Pontine Gliomas (DIPGs) at Initial Diagnosis, Post-Radiation Therapy and at Time of Progression (for patients at the age of 2 – 39)
  • PNOC023: Open label Phase 1 and target validation study of ONC206 in children and young adults with newly diagnosed or recurrent diffuse midline glioma (DMG), and other recurrent malignant brain tumors (for patients at the age of 2 – 21)
  • PNOC019 (currently on hold): A Randomized, Double-Blinded, Pilot Trial of Neoadjuvant Checkpoint Inhibition followed by Combination Adjuvant Checkpoint Inhibition in Children and Young Adults with Recurrent or Progressive High Grade Glioma (HGG)
  • PNOC026: A Phase 2, Open-Label, Multicenter Study to Evaluate the Safety and Efficacy of the Oral Pan-RAF Inhibitor DAY101 in Pediatric Patients with BRAF-Altered, Recurrent or Progressive Low-Grade Glioma

 

 

 

 

 

Supporters and Partners

 

Supporters of the DIPG/DMG Center Zurich

  • Swiss to cure DIPG
  • Swiss National Science Foundation
  • Borne Hjernecancer Fonden
  • Tarbaca Indico Foundation
  • The ChadTough Foundation
  • Yuvaan Tiwari Foundation
  • Michael Moisier Foundation Defeat DIPG
  • Mithil Prasad Foundation
  • Storm The Heavens Fond
  • We love you Connie Foundation
  • Cannonball Kids' Cancer Foundation
  • Kortney Rose Foundation
  • Minderoo Foundation
  • Rising Tide Foundation
  • PNOC Foundation
  • Anticancer Fund

DIPG/DMG Center Partners

  • Pacific Pediatric Neuro-Oncology Consortium (PNOC)
  • Children's Brain Tumor Network

 

 

Donate

 

If you like to support the DIPG/DMG Center of Zurich please contact glioma@kispi.uzh.ch for details. Funds will be used to support clinical studies as well as translational approaches.

 

 

 

DMG-ACT

 

DMG-ACT: Diffuse Midline Glioma-Adaptive Combinatory Trial. Leading the DMG Center in Zurich, Dr. Mueller and Dr. Nazarian developed the first PNOC working group for DMG and established the DMG-ACT program.

DMG-ACT is a biology driven trial platform conducted through PNOC Global. The working hypothesis of DMG-ACT is that a progressive clinical trial platform that is both adaptive to new data from the laboratory, as well as ongoing correlative studies focused on combinatorial therapies, will allow for more rapid progress in the clinical care of children and families suffering from DMG compared to traditional approaches. Thus, our goal is to test combination treatment approaches in a variety of DMG model systems and multiple laboratories around the world and by leveraging complementary expertise.

DMG-ACT program:

  • Is governed by experts from over 47 institutions across Australia, Europe, and North America
  • Aims to enhance preclinical assessments of potential therapeutic strategies in a variety of DMG models
  • Will assess data reproducibility in laboratories around the world
  • Has built a direct link between clinical research and preclinical research by enhancing correlative assessment
  • Is adaptive to new data generated from the trial as well as from biomedical science investigations, so that new discoveries can be integrated into the care of each patient
  • The DMG-ACT trial will perform extensive correlative studies such as cerebrospinal fluid and tumor tissue analyses for each child enrolled in the trial

 

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