Reports
The
Medulloblastoma
Initiative
Impact Report - September 2024
Making History Together
The Medulloblastoma Initiative (MBI) was born with a bold mission: to find a cure for the most common malignant pediatric brain tumor. This tumor affects 25,000 children every year and, unfortunately, it struck my son Frederico in 2015, when he was only 9 years old.
It was then that I realized, in the hardest way possible, that children with brain tumors had been left behind. The current treatment, developed in the 1980s, is highly toxic and ineffective. Many children perish, and those who survive suffer from severe side effects for the rest of their lives.
Some years later, when a routine exam showed that the tumor had recurred, I was informed by the doctors that there were no more protocols available to treat Frederico. Research has barely advanced in the last forty years.
Refusing to accept this sad state of affairs, I reached out to Dr. Roger J. Packer at Children's National Hospital in Washington, D.C. From this connection — made only three years ago — a Consortium was formed that now includes 14 laboratories affiliated with universities in the United States, Canada and Germany.
The innovative model adopted by the MBI has proven successful. All resources are directed to the laboratories that make up the Consortium, which work collaboratively and synergistically. Each has its piece of the puzzle, and all are led by Dr. Packer.
In just two and a half years, we gained U.S. Food & Drug Administration approval to commence two clinical trials. We anticipate approval for three more trials in the next 18 months. This represents unprecedented speed. We are making great strides toward finally finding a cure and saving the lives of thousands of children.
Crucial factors got us to where we are today: the experience and leadership of Dr. Packer, the quality and competence of the scientists involved, the endorsement of Children's National and my determination to find a cure.
However, none of this would be possible without your incredible generosity. Thank you for believing in our cause and trusting our innovative model. Together, we are making history through our fight against childhood cancer. Thank you very much!
Fernando Goldsztein
Founder, The Medulloblastoma Initiativ
First Goal Reached:
Two Clinical Trials Approved
The MBI began its work in late 2021 by asking some difficult questions: can we speed the arrival of new therapies for brain tumor patients? Can we offer hope to young patients who lack treatment options? Might cures be just around the corner after decades without progress?
This spring we learned the answer — a clear and resounding YES. Less than 30 months after its founding, the MBI reached one of its most important objectives. It opened the door to two new FDA-approved clinical trials of potential treatments for relapsed Group 4 medulloblastoma. Both are led by investigators from the University of Florida and funded by the MBI. Each represents the first human trials of their kind.
Trial 1: MATCHPOINT
Approved on February 29, 2024
Will test an immunotherapy that uses a patient’s own T cells in combination with a drug that breaks down the tumor’s resistance to treatment.
Trial 2: An RNA vaccine trial
Green-lit on April 9, 2024
Will explore if patients can develop immunity to relapses through an mRNA vaccine similar to those developed for COVID-19.
Principal Investigator, Cure Group 4 Consortium
MATCHPOINT:
Has medulloblastoma met its match?
Duane Mitchell, MD, PhD, co-director of the University of Florida’s Preston A. Wells Jr. Center for Brain Tumor Therapy, leads the MATCHPOINT trial. The therapy harnesses adoptive cell therapy (ACT), which programs a patient’s T cells (white blood cells critical to the body) to seek and destroy cancer cells. In a previous study (ReMATCH), Dr. Mitchell’s lab demonstrated ACT’s significant promise as a safe and effective treatment for relapsed medulloblastoma. One patient saw a nearly total elimination of widespread metastatic disease.
MATCHPOINT will test this technique in an initial pilot study of six patients with relapsed Group 4 tumors. Dr. Mitchell seeks to amplify the ACT’s effectiveness by combining it with an immune checkpoint blockade. This drug revents the tumor from protecting itself with immune checkpoints. In a checkpoint, the tumor cell binds with an immune cell and sends a stop signal to the attacking T cell. The blockade drug eliminates this line of defense, which increases the immunotherapy’s effectiveness.
“The ultimate goal is we want to cure kids with brain cancers and see immunotherapy treatments move into frontline treatments to perhaps avoid or diminish some of the toxicities of standard treatments we use now,” says Dr. Mitchell. He anticipates patient recruitment by fall 2024.
A Revolutionary Vaccine
“Recurrent medulloblastoma in nearly every form is fatal,” says Elias Sayour, MD, PhD, a pediatric oncologist and researcher at the University of Florida. “We are in this to provide hope that we can move the needle.” Dr. Sayour’s highly original research, which combines mRNA and nanotechnologies with the goal of curing pediatric brain tumors, is gaining global attention. In May 2024, Cell — the world’s most prominent biology journal — published results from his first-ever trial of mRNA vaccines to treat adult glioblastoma (another aggressive and deadly brain cancer).
The MBI’s investment enables Dr. Sayour to bring this pioneering approach to relapsed Group 4 medulloblastomas. The vaccine uses mRNA and lipid nanoparticles, similar to COVID-19 vaccines, but with two key ifferences. First, it draws upon a patient’s own tumor cells to create a personalized vaccine. Second, it uses nanotech to build a unique delivery mechanism within the vaccine. The combination promises to reprogram a patient’s immune system to attack the cancer.
The upcoming trial will recruit relapsed Group 4 medulloblastoma patients after evaluating the vaccine — previously tested in adults — on a pediatric patient with a glioma. This will help validate safety before proceeding to medulloblastoma patients. Dr. Sayour anticipates the Group 4 trial will open in spring 2025.
The Power of New Approaches
The MBI fosters far more than synergy and collaboration through its Cure Group 4 Consortium. It gives investigators across its 14 labs in Canada, Germany and the U.S. the priceless opportunity to think boldly without fear of failure. “You can't start a fire without kindling. Resources from the MBI provide kindling for discoveries,” says Michael Taylor, MD, PhD, FRCS(C), a globally renowned authority on the genetic origins of medulloblastoma. Dr. Taylor leads a Consortium lab at Texas Children’s.
Government funding agencies, such as the National Institutes of Health (NIH), tend to fund only proven ideas, he says. The MBI’s power comes from opening the space for unproven ideas with the potential to transform the field. “By getting most of the world’s experts on Group 4 medulloblastoma in the same room, we can go through the ideas and prioritize the ones that are good, and quickly discard the ones that are wrong or not likely to work.”
Dr. Taylor’s colleagues across the Consortium agree. “The MBI has made the whole field of medulloblastoma research talk about Group 4 tumors,” says Vijay Ramaswamy MD, PhD, FRCPC, of SickKids Toronto. “Once we start putting out papers on Group 4, more investigators become interested in it.” This speeds progress for treating Group 4 tumors, which remain understudied despite representing approximately half of all medulloblastomas, he says.
The MBI’s first two clinical trials benefitted from this openness to trailblazing ideas, which fosters breakthroughs. This summer, Dr. Taylor published the discovery of a chimeric antigen receptor T cell (CAR T) approach to arrest the growth of Group 3 medulloblastoma. The prestigious journal Cell published these landmark findings in August 2024. He hopes that this discovery will open the door to new immunotherapies that prevent and cure Group 4 tumors.
Connection Makes a Difference
The MBI began with a single connection between a father and a doctor. Fernando Goldsztein reached out to Dr. Packer at Children's National to ask what he could do to change the future for children with medulloblastoma.
Just like Fernando, the Ellis family — featured in previous reports — took their own first step in 2023. After learning about the MBI, they reached out to friends and family to launch their first fundraising effort. They have more than tripled their goal — raising more than $100,000 — and hope to share their experience with other families. We are proud to share their easy to-use tips summarized in our new fundraising guide for families: The Handbook of Hope. We invite you to check out the guide and take your first step! We look forward to having you as part of our journey.
The MBI at the Brazilian Embassy in Washington, D.C.
A beautiful April 2024 evening set the stage for our night of awareness, hosted by Ambassador of Brazil to the United States Maria Luiza Ribeiro Viotti. Fernando Goldsztein (the MBI founder), Dr. Roger Packer (PI, Cure Group 4 Consortium), and Michelle Riley-Brown (Children’s National President and CEO) spoke about the MBI’s accomplishments for children with brain tumors. Fox News journalist and anchor Bret Baier skillfully moderated the conversation.
This event marked the third in a series of groundbreaking contributions made by the MBI to raise awareness. In March 2024, the MBI joined the Permanent Council of the Organization of American States (OAS) for a World Rare Disease Day session. The event represents 300 million people affected by rare diseases around the world. Later that month, the Cure Group 4 Consortium presented at SNOLA 2024, the largest scientific event in neuro-oncology in Latin America, held in the city of São Paulo, Brazil.
Sharing our message of hope to as many audiences as possible is a part of our mission. This can only be accomplished with support from dedicated partners. Thank you for being a part of our movement.
Walk or Run a 5K This Fall With the MBI —
No Time to Lose
You can help the MBI by joining team No Time to Lose at the Race for Every Child. Children’s National will host the event in Washington, D.C., and virtually around the world, on October 19, 2024.
Joining our team is easy and free to register through October 13. There’s no commitment to give personally, but we would like you to spread the word to your friends and families. You can run or walk the 5K distance wherever you are, or you can choose not to run or walk at all. We have an ambitious goal of raising $100,000 to support medulloblastoma research — including our recently launched clinical trials of new therapies.
Please join us. It’s an easy step to take that will make a huge difference for families worldwide confronted by medulloblastoma.
A Mother’s Support
By Francesca Tantazzi
Almost 20 years ago, I gave birth to a lively little girl named Caterina. I remember how she played with her dolls at home in Rome, Italy, and frolicked in the sand during vacations in Sardinia.
Life was good. Yet one summer day in 2008, my daughter — then two and a half — suddenly lost her balance. Within days, we received a devastating diagnosis: medulloblastoma. This began a harrowing period in our lives. A surgery left Caterina partially paralyzed. Chemotherapy and an autologous stem cell transplant were hard, but they gave us hope.
Every parent lives for hope, but our time with Caterina after treatment was short-lived. By spring, her tumor relapsed. Despite radiotherapy, doctors informed us that no other treatments existed. I remember wishing there were more options — that there was something we could do.
We said goodbye to Caterina in 2009. Later, my husband wrote a book about her in Italian called “Caterina’s Flight.”
Last year, I came across the MBI through a social media post. It awakened a desire within me to make a difference. For the first time, I realized there might be hope for other children suffering from this terrible disease. The collaboration among some of the world's top researchers impressed me. I also was struck by Fernando's determination and ability to mobilize resources.
Years of healing have strengthened me and given me perspective. Today, I’m using my voice to grow our community in support of the MBI. Together, we can do more than hope. We can act so families like mine will finally have good options.
“There is a Signal Here”:
Drug Development Progress
Consortium scientists continue to make progress on molecularly targeted treatments. This effort seeks to identify and disrupt pathways that drive tumor growth. Dr. Ramaswamy of SickKids Toronto recently made a series of promising findings that may lead to breakthroughs. The team identified the PI3K signaling pathway as key to Group 4 tumor growth, including during metastasis.
They tested Rapalink, a drug targeting this pathway, and found it extended test specimen survival by more than 70 percent in preclinical models. Rapalink connects rapamycin — a potent bacterial compound that can inhibit cellular growth — with mTOR, the protein complex that it targets to inhibit cell growth.
Two decades ago, rapamycin-related drugs transformed the field of transplant medicine. They enabled patients to safely accept new organs. They may ultimately have a similar impact for patients with tumors. The team plans to refine their testing of the drug at lower doses and in combination with other therapies to pave the way for clinical testing.
Testing Potential Cures:
The MBI Welcomes Its 14th Lab
Drug discovery also is central to the arrival of the newest Consortium lab in 2024. William A. Weiss, MD, PhD, leads one of the world’s foremost labs for developing brain tumor models and testing novel therapies at the University of California San Francisco. Dr. Weiss previously served as a Consortium advisor and has authored more than 35 significant papers with Dr. Taylor at Texas Children’s.
Together, Drs. Weiss and Taylor will build disease models and test drugs based on the pair’s observations of how medulloblastoma begins in young human brains. They hypothesize that medulloblastoma develops in ways distinctive to human cells. Growing human Group 4 tumor cells in culture and building 3D models of tumors using organoid technology will enable them to test this theory rapidly. Dr. Weiss uses gene-editing and stem cell technology to build these models.
Augmenting Cell Therapy With Focused Ultrasound
As detailed in previous reports, Dalia Haydar, PharmD, PhD, of Children’s National, develops CAR T cells to recognize, target and destroy tumor cells. In the last year — in part through the MBI’s support — Dr. Haydar fully staffed her seven-member lab. “Now that I have a team, we are pursuing a vision to drive rapid progress,” she says.
Her lab enhances these CAR T cells to fight tumors more effectively and explores ways to overcome tumor environment challenges. One approach involves focused ultrasound. This non-invasive technology uses high- or low-intensity sound waves (HIFU or LIFU) to precisely target and disrupt specific areas in the brain, which in turn can help spark an immune response to destroy the tumor. This response can boost the CAR T cell treatment effectiveness, which leads to better lifetimes for patients.
Dr. Haydar recently received a $600,000 grant from the U.S. Department of Defense to study LIFU’s ability to enhance treatment for Group 3 and Sonic Hedgehog medulloblastoma. The technique aims to temporarily open the blood-brain barrier and improve the delivery of therapeutics. She plans to translate her findings for Group 4 patients with the MBI’s support.
The potential of focused ultrasound can contribute significantly to the overall impact of the Consortium. “Although we are trying to combat this disease from different angles, we are all after the same goal,” she says. “We all learn from the different tools used by each researcher. We have the potential to conduct combined clinical trials using CAR T cells, vaccine, focused ultrasound and a medicine. I think all the discoveries are
will complement in a very positive way.” Doing so promises to improve the standard of care for thousands of children battling brain cancer around the world.
