The following article originally appeared on thecurestartsnow.org
The Cure Starts Now Foundation funds novel trial that halts tumor growth in 2/3 of study
CINCINNATI | February 18, 2021 – The Cure Starts Now announced that the Polyamine Pathway Metabolism as a Novel Therapeutic Option for Diffuse Intrinsic Pontine Glioma (DIPG) grant, funded in partnership with the DIPG/DMG Collaborative, has resulted in the identification of a potentially revolutionary new drug treatment for brain cancer.
In pre-clinical mouse model testing, researchers found the promising drug combination of Difluoromethylornithine (DFMO) and AMXT 1501 led to the survival of two-thirds of the mice and that it stopped the growth of DIPG tumors in the mice. This drug therapy is the most effective treatment ever tested in laboratory models of this highly aggressive and incurable pediatric cancer.
“When you combine these two drugs, the result is really spectacular,” said lead researcher and pediatric oncologist Dr. David Ziegler from the Children’s Cancer Institute and Sydney Children’s Hospital. “What we've seen is, actually, what we think is the most active drug that anyone's ever tested in the lab for DIPG and the tumors stop growing.”
“Breakthroughs like this one are part of the reason we founded The Cure Starts Now,” said Brooke Desserich, Executive Director of The Cure Starts Now. “They provide parents with much-needed hope and move us immensely closer to finding the elusive cure for this horrific brain cancer. We are so proud of Dr. David Ziegler and his wonderful team of researchers. We can’t wait to start clinical trials.”
This is all part of The Cure Starts Now’s 12-year plan focusing on the Homerun Cure™ for all cancers. The belief behind this strategy is that to truly cure all cancers you have to first focus on those cancers that are immune to treatment, affect children, and are the biggest bullies with the highest death rate. With DIPG checking all three boxes, it became the focal point. The Cure Starts Now then adopted a generational funding strategy approach, effectively not only funding “test tube” grants, but also making the necessary preparations setting up concurrent clinical trials and bringing together the expertise to deliver results at three times the speed.
“For us, cancer research is like a relay race,” said Keith Desserich, Chairman of The Cure Starts Now. “It’s not just enough to beat cancer on the first lap – you have to also have the next person ready to take over for the second one and until you finish the race. I guess that’s just what we try to do differently: we believe it requires a long-term focus that not only identifies targets, but brings together researchers and then figures out how to make it work for the patient.”
In 2018, The Cure Starts Now identified this novel approach in Australia by Dr. Ziegler, seeking to block the polyamine pathway and stop the growth of DIPG tumors. After funding the grant, the charity began looking toward the future and, in the event that the lab research was a success, already started efforts to deliver the promising drug combination into clinical trials over the next four years through the CONNECT Consortium, an international collaborative network of pediatric cancer centers, so that it would be available in 15 countries to children in the fight against this horrific cancer.
With the success of Dr. Ziegler’s pre-clinical mouse model testing, The Cure Starts Now’s long-term strategy has sped up the test-tube to bedside timeline by nearly three times, effectively ensuring that the wait between each step in the process is as minimal as possible.
Dr. Ziegler said that clinical trials of the drug combination in DIPG are planned to begin this year in children in a global study led by the Children’s Cancer Institute and, in combination with, the CONNECT Consortium, which is operational funded by The Cure Starts Now, the Brooke Healey Foundation and the Reflections of Grace Foundation.
About The Cure Starts Now
The Cure Starts Now was started in honor of 6-year-old Elena Desserich, a Cincinnati girl who battled a rare, aggressive form of brain cancer known as DIPG. Today, The Cure Starts Now Foundation has over 40 locations in three countries and is the only cancer foundation dedicated to finding the Homerun Cure™ for cancer by focusing on one of the rarest, most aggressive forms of cancer. Believing in more than just awareness, The Cure Starts Now has funded over $16.4 million in cancer research in partnership with the DIPG Collaborative. This includes 100+ cutting edge research grants at over 100 hospitals in 15 countries since 2007. Learn more about The Cure Starts Now and their mission to find the Homerun Cure™ for cancer at www.thecurestartsnow.org, and follow www.facebook.com/TheCureStartsNow/ for updates.
Dr. David Ziegler and Dr. Maria Tsoli discuss their research team’s groundbreaking discovery into the treatment of DIPG, and what it may mean for children who are diagnosed with this disease. This project is the result of the Polyamine Pathway Metabolism as a Novel Therapeutic Option for Diffuse Intrinsic Pontine Glioma grant that was originally funded in 2018 by The Cure Starts Now and The DIPG Collaborative for $175,089. The grant was designed to investigate vulnerabilities in these types of tumors and to pair it with a drug.
Dr. David Ziegler: “DIPG is the most common, what we call high-grade glioma that occurs in children. It peaks in children at about the age between five and seven years. Usually comes on very quickly over a couple of weeks, sometimes just with very mild symptoms. The outcome for these kids is terrible. And we have to go and tell their parents really what's one of the hardest conversations in the world to have. Which is that, essentially, your child has an incurable disease. Essentially, almost all of these children will die, usually within about a year of that diagnosis.”
Dr. Maria Tsoli: “One of the key challenges for us researchers has been the fact that we haven't had any biological material to do any drug testing.”
Dr. David Ziegler: “Several years ago, we set up a tumor donation program. The parent could offer to have that tumor collected and put in our tumor bank. And, actually, allow research to be performed on these tumors for the first time in Australia, to start to come up with new treatments.”
Dr. Maria Tsoli: “We have found a few drugs that seem to be remarkably effective at reducing the growth of DIPG tumors.”
Dr. David Ziegler: “We have been working on drugs that target what's called the polyamine pathway.”
Dr. Maria Tsoli: “Our team has found two drugs. Difluoromethylornithine (DMFO), a drug that stops the synthesis of polyamines, and AMXT-1501, a drug that stops the polyamines from entering the cells. Together, in combination, are being very effective at stopping the growth of DIPG tumors.”
Dr. David Ziegler: “When you combine these two drugs, the result is really spectacular. What we've seen is actually what we think is the most active drug that anyone's ever tested in the lab for DIPG and the tumors stop growing.”
Dr. Maria Tsoli: “The next steps will be to take this therapy to the clinic. And offer it to children with DIPG, through Phase 1 and Phase 2 clinical trials.”
Dr. David Ziegler: “We're working very closely with the company who's making this new drug. We're working with international researchers and clinicians from around the world. We're aiming to open the trial in the next year. Which, for the first time, will offer this new treatment for children with DIPG and other brain tumors as well.”
Dr. Maria Tsoli: “I would like to thank a lot of philanthropic associations and funding agencies for believing in this work.”
Dr. David Ziegler: “It's only thanks to the support we get through the community and through parents and fundraisers and other groups that allow us to keep this research going, and to do what we do. When we started this program in DIPG, it was driven really by the parents.”
Dr. Maria Tsoli: “And without them, we wouldn't have been in the position of being able to do any testing and more importantly, identify this particular treatment.”
Dr. David Ziegler: “We believe this is one of the first really important breakthroughs. And, ultimately, we won't be having those conversations with parents anymore saying, ‘This is incurable, there is no hope.’ But for the first time we will start to offer hope. For the first time, we'll start to offer cures. That's what we are going to keep working towards until we reach that goal.”
In summary, this promising new drug combination has the potential to change the way DIPG is treated and possibly stop the growth of the horrific tumors by blocking the transport of polyamines into DIPG cells. This type of breakthrough is the reason The Cure Start Now was founded. It provides parents with much needed hope and moves us immensely closer to finding the elusive cure for this monstrous brain cancer.