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Duane Mitchell, MD, PhD, leads the MBI’s first FDA-approved clinical trial at the University of Florida.

Making History: Our First Clinical Trial Begins

The Medulloblastoma Initiative (MBI) is helping transform the field of brain tumor research. This spring, investigators at the University of Florida launched the MBI’s first clinical trial.

“We dreamed this moment would come,” says Fernando Goldsztein, the MBI’s founder. “Our first trial shows what we can accomplish together. Thanks to the MBI’s supporters, children facing incurable tumors finally have new hope. We have the potential to save thousands of lives, and we will not stop at one trial. We have no time to lose.”

The Florida team calls the first trial, which the U.S. Food and Drug Administration (FDA) approved last year, MATCHPOINT. The innovative treatment combines a patient’s T cells with a drug that helps the immune system overcome the tumor’s defenses, paving the way for groundbreaking advancements in cancer therapy.

Please use this QR code to learn more about recruitment for the MATCHPOINT trial

In March, recruitment for the trial began in Florida. Additional recruitment at Children’s National Hospital in Washington, D.C., will start soon. The trial enrolled its first two patients in May. It plans to admit 12 patients over the next two years.

MATCHPOINT aims to eliminate relapsed tumors by targeting them precisely from multiple angles. “RNA gives us a blueprint for what proteins are made within tumor cells,” says Duane Mitchell, MD, PhD, who leads the trial. “For the last decade, my team has developed genetic technologies that harness this blueprint to personalize immunotherapy treatments. The trial will use these treatments in combination with drugs that remove the tumors' self-defense mechanisms. This promises to allow us to attack and eliminate the tumor cells that can't be removed by surgery.”

MATCHPOINT shows the way forward. The MBI will not rest until we have effective treatments for relapsed medulloblastoma. I am grateful to our worldwide community of supporters who have joined our movement. Together, we are changing the world by fueling collaborative science with one aim: finding cures.

— Fernando Goldsztein MBI founder

This is a real opportunity. It’s phenomenal that the trial is open. It could have a real payoff, not only for patients in this trial but also for other projects across the Consortium.

—

Roger

Packer, MD Director, Brain Tumor Institute, Children’s National Hospital, Washington, D.C.; Principal Investigator, Cure Group 4 Consortium

MATCHPOINT is one of two FDA-approved clinical trials at the University of Florida made possible by the MBI's investments. The second trial, scheduled to begin later this year, will test an mRNA vaccine similar to those developed for COVID-19. The innovative approach, led by Elias Sayour, MD, PhD, has the potential to generate a robust immune response in patients to prevent tumor recurrence.

With the MBI’s support in the coming months, Dr. Mitchell plans to launch a third trial that takes MATCHPOINT one step further. He has developed a novel artificial intelligence platform that has the potential to supercharge immunotherapy by targeting tumors with far greater precision.

Your Support Fuels Hope

The MBI and Children’s National Hospital present this report with deep appreciation for your support or interest in joining our global movement. We will change the grim reality that medicine has few answers for the one out of every three medulloblastoma patients whose tumors return after treatment. Thank you for helping us transform our understanding of the most common malignant brain tumor in children.

AN URGENT MISSION:

Sa ve Child re n’s Li ves

MEDULLOBLASTOMA:

The most common pediatric brain tumor

No established treatment for relapse which is almost always fatal

Many kids who surv ive experience lifelong physical and cognitive impairment

Treatment protocols remain largely unchanged since the 1990s

9 years old is the average age of diagnosis

A “New Playbook” for Cures

In January, MIT News highlighted the MBI’s approach as a ‘new playbook’ for disrupting the standard way of developing cures for childhood diseases. Critical to this new playbook is the MBI’s global dream team of 14 labs working side by side: the Cure Group 4 Consortium.

In the article, Dr. Packer outlined this innovative model. “We set up a Consortium of leading institutions around the world doing medulloblastoma research, asked them to change their lab approach to focus on the Group 4 tumor, and assigned each lab a question to answer,” he says. “We charged them with coming up with therapies, not in seven to 10 years, which is the normal transition from discovery to developing a drug and getting it to a patient, but within a two-year timeline.”

“That highly ambitious goal led to extraordinary results,” Dr. Packer adds today. “We will benefit from the MBI’s full impact for generations.”

A Global Dream Team

University of Michigan Ann Arbor, MI

McMaster University Hamilton, Ontario, Canada

Columbia New York City SickKids Toronto, Canada

University of California San Francisco CA

Children’s National Hospital Wash ngton, DC Texas Children’s Hospital Houston DC

Emory University School of Medicine Atlanta, GA

University of Florida Gainesvi le, FL

Consortium Scientists

Roger J. Packer, MD Children’s National Hospital

Eugene Hwang, MD Children’s National Hospital

Robert Wechsler-Reya, PhD Columbia

Duane Mitchell, MD, PhD University of Florida

Elias Sayour, MD, PhD University of Florida

Michael Taylor, MD, PhD, Texas Children’s Hospital

Vijay Ramaswamy, MD, PhD SickKids

Craig Daniels, PhD SickKids

Yanxin Pei, PhD Children’s National Hospital

Brian Rood, MD Children’s National Hospital

Sheila Singh, MD, PhD McMaster University

Tobey MacDonald, MD Emory University School of Medicine

Lena M. Kutscher, PhD German Cancer Research Center

Stefan Pfister, MD German Cancer Research Center

Dalia Haydar, PharmD, PhD Children’s National Hospital

Javad Nazarian, PhD Children’s National Hospital

Carl Koschmann, MD University of Michigan

William A. Weiss, MD, PhD University of California San Francisco

São

Brazil

14 laboratories constitute our Cure Group 4 Consortium

18 scientific leaders

3 of 5 of the most cited experts* in medulloblastoma research *expertscape.com

German Cancer Research Center Heidelberg Germany

Santa Marcelina Hospital (advisor)

Paulo,

Organoid Research: The Missing Link for Curing Hard-to-Treat

Tumors?

Part of the MBI’s lasting impact for children everywhere will come from new insights into medulloblastoma’s molecular fingerprint. While clinical trials may yield new therapies today, breakthroughs from preclinical studies have just as much potential to transform the field. Although new drugs are usually tested in animal models, four MBI investigators have recently pursued a different approach: organoids.

Organoids are three-dimensional cell structures created in the laboratory. Scientists generate them using stem cells or patients’ tissue samples. They can develop into complex, multicellular structures that resemble specific tissues or organs. This holds great potential for brain tumor research, particularly in the case of Group 4 medulloblastoma.

“What if the cell origin of Group 4 doesn’t exist in mice?” asked MBI investigator Robert WechslerReya, PhD, of Columbia University at a Consortium meeting earlier this year. That’s a real possibility because the disease's cell of origin—the unipolar brush cell (UBC) progenitor—is exceedingly rare in mice. Unlike human UBC cells, those in mice do not divide. This makes them unlikely to give rise to tumors. The inability to generate mouse models of Group 4 has made it challenging to identify and test novel therapies for the disease. MBI investigators believe it may be easier to create models using organoids.

Consortium member Michael Taylor, MD, PhD, FRCS, of Texas Children’s laid the groundwork for this hypothesis by helping to discover the cell of origin, findings published in the prestigious journal Nature. Now, four Consortium investigators are developing organoids to test their potential:

• Dr. Wechsler-Reya at Columbia

• Lena M. Kutscher, PhD, at the German Cancer Research Center

• Yanxin Pei, PhD, at Children’s National

• William A. Weiss, MD, PhD, at the University of California, San Francisco

Dr. Pei has achieved significant progress in developing an organoid specific to medulloblastoma. In recent months, her lab developed cerebellar organoid tissue, confirmed the presence of UBC, and found two oncogenes (genes with the potential to cause cancer) that can make organoid cells grow. Her lab is currently testing the organoid to verify that these cells resemble Group 4 medulloblastoma.

Dr. Kutscher is taking a different approach, in keeping with the MBI’s streamlined approach that avoids duplicating research. “We don’t have animal models for many of the patient tumors we see,” she says. “We hope that organoids will fill that gap.” Dr. Kutscher labels the UBC progenitors and concentrates them in an organoid. This creates the possibility of a drug testing model that’s highly specific to Group 4. This could provide the missing link to therapeutic breakthroughs and faster progress for children with tumors.

“The MBI’s investment in basic science alongside preclinical and clinical researchers will make a difference,” Dr. Kutscher says. “We are all working toward a common goal of developing cures.”

Reflections from Frederico’s Journey

My son Frederico’s medulloblastoma was the spark that launched the MBI. He continues to inspire my efforts to help children everywhere. With his permission, we share this collection of his photography. To me, Frederico’s photos offer windows into his journey.

— Fernando Goldsztein

A Key Asset for Clinical Trials: Liquid Biopsy

The MBI lab at Children’s National, led by Javad Nazarian, PhD, continues to refine a liquid biopsy platform. Dr. Nazarian is at the vanguard of this emerging technology, which allows clinicians to detect and track tumor development with a simple body fluid sample. For Group 4 patients, he plans to use cerebrospinal fluid (CSF), a clear, plasma-like liquid surrounding the brain and spinal cord. Evidence suggests that CSF may provide more accurate information than traditional tissue samples. For the patient, drawing a CSF sample involves less discomfort, less time and lower cost than a conventional tissue biopsy.

Liquid biopsy also promises to supercharge research just as the MBI begins to test novel therapies. “We want to respond to early successes and failures as we go into clinical trials,” Dr. Packer says.

“Our goal has been to push research platforms to the clinical setting,” Dr. Nazarian says. His team seeks Clinical Laboratory Improvement Amendments certification for the Group 4 liquid biopsy platform. This designation ensures the quality and accuracy of human laboratory tests. “Certifying these tests will be a major step forward in moving our research into clinical care.”

Other Scientific Updates

Scientists from the 14 Cure Group 4 Consortium labs met in early 2025 to discuss their latest progress. Highlights included:

• Dalia Haydar, PharmD, PhD, a researcher at Children’s National specializing in chimeric antigen receptor T-cell (CAR T-cell) immunotherapies, reported promising preclinical findings on combining CAR T-cell treatment with ultrasound waves to enhance tumor penetration. “The combination allows us to safely and efficiently deliver CAR T cells systemically—something that isn’t possible without focused ultrasound,” Dr. Haydar explained. She outlined future work with Brian Rood, MD, also of Children’s National, to refine targets for this approach.

• Vijay Ramaswamy, MD, PhD, FRCPC, at SickKids Toronto, continues to make progress testing Rapalink, a drug targeting the pathway Group 4 tumors use to grow. Initial studies indicate that the drug may work well with other therapies. His laboratory is conducting preclinical testing this spring to develop a clinical trial for combination therapy.

Thank You

The entire MBI team thanks you for supporting our mission or your interest in learning more. We are on the cusp of breakthroughs, an accomplishment made possible by our community’s collective action. Your support will make a difference for patients everywhere. Together, we will save lives and improve lifetimes.

Testimonials

Group 4 tumors are the most common form of medulloblastoma. It’s very important to go after them since we don't understand them as well as the other types. It requires deep investigation. These are the experts to do it. The Cure Group 4 Consortium is a great team, and they are making real progress. Dr. Mitchell’s trial is amazing. He will get things done.

— Scott Pomeroy, MD, PhD

Member, Cure Group 4 Consortium Advisory Board; Neurologist-in-Chief, Emeritus; Chair Emeritus, Department of Neurology; Bronson Crothers Professor of Neurology, Harvard Medical School

The MBI represents a critical and focused effort to address a devastating childhood cancer. Its commitment to accelerating the pace of discovery and bringing innovative therapies to children with medulloblastoma by fostering collaboration among researchers, clinicians and patient advocates aligns perfectly with the American Society of Clinical Oncology (ASCO)’s mission to conquer cancer through research, education and promotion of the highest quality patient care. ASCO and our Conquer Cancer Foundation wholeheartedly support the MBI's vital work and its potential to make a significant impact on the lives of children and families facing this challenging diagnosis.

— Clifford Hudis, MD, FACP, FASCO Chief Executive Officer, American Society of Clinical Oncology

The MBI is exactly the kind of highly focused, talent-rich, smartly resourced research consortium that is necessary to rapidly accelerate the pace of developing treatments for one of the toughest brain cancers facing children, Group 4 medulloblastoma. The MBI leadership team is wisely bringing together the brain tumor community to build a groundswell of interest and support that fuels hope and gives research the best chance of turning the previously untreatable into the potentially curable.

— David Arons, JD President & Chief Executive Officer, National Brain Tumor Society

I recently came across the MBI, a Brazilian-led effort that truly caught my attention for its innovative approach. The project now combines 14 institutions across the United States and other parts of the world with a bold and efficient structure. It has succeeded in mobilizing some of the world’s leading scientists and is already achieving impressive results. I joined this initiative because I believe in its transformative potential. It has everything it takes to make a real difference in the future of many children.

— Luis Stuhlberger Chief Executive Officer of Verde Asset Management, philanthropic supporter of the MBI

Report #8

The Medulloblastoma Initiative

Fernando Goldsztein: Founder

Mauro Dorfman: Strategic Leader

Claudia Buchweitz/Scientific Linguagem: Team Leader

Iago Paz/Scientific Linguagem: Design and Social Media

Martina Fischer: Project Manager

Francesca Tantazzi: Advisor

Jyothi Raghavan: Community Leader

Katherine Fontan: Desk Research

Fbiz: Advertising and Social Media

Digital Trix: Press and PR Brazil

Sunshine Sachs Morgan & Lylis: Press and PR USA

Whoever

-The Talmud

saves one life saves the world entire."

External Scientific Advisory Board

Sidnei Epelman, MD, Santa Marcelina Hospital, São Paulo, Brazil

Stewart Goldman, MD, Phoenix Children's Hospital, University of Arizona

Scott Pomeroy, MD, PhD, Boston Children’s Hospital, Harvard Medical School

Rajeev Vibhakar, MD, PhD, MPH/MSPH, Children’s Hospital Colorado, University of Colorado

Children’s National Hospital Foundation

MBI Advisory Board

Paula Puppi

Claudio Galvão de Castro

Ricardo Sales

Claudia Buchweitz

Mauro Dorfman

Fernando Goldsztein

Mandy Ranalli: Associate Vice President, Major, Principal and International Giving

Andrew Miller: Director of Development, Neurosciences & Behavioral Medicine

Erin Whiteman: Associate Director, Major Gifts

Paige Mulry: Development Coordinator, Major Gifts and International Advancement

Emma Younger: Development Assistant

Fernando Goldsztein appeared on Fox 5 news in Washington, D.C., during Brain Tumor Awareness Month in May to highlight the MBI's efforts to find new cures.