News About The Cure
Researcher Spotlight: Dr. Bakhos Tannous of Massachusetts General Hospital
January 9, 2018
John Mackintosh - The Cure Starts Now Massachusetts
WHY ARE YOU INTERESTED IN DIPG?
My research background is to study adult gliomas. I became interested in DIPG after witnessing the son of a dear friend of mine diagnosed with DIPG with no cure and very low survival rate.
YOU ARE STUDYING AN ANTI-MALARIA DRUG TO TREAT DIPG. WHY?
We tested many existing drugs on DIPG cells and discovered that Mefloquine is effective and potent in killing DIPG cells in all cultures tested. Mefloquine is the anti-malaria drug of choice for US Military deployed overseas and for travelers. We have preliminary results in DIPG cell cultures and mouse models that shows low dose Mefloquine restricted DIPG growth and improved their survival.
WHAT ARE THE BENEFITS OF RE-PURPOSING AN EXISTING DRUG TO TREAT DIPG?
There are several. Mefloquine has already been demonstrated to be safe for use in humans. So we do not need to prove that. It is FDA approved and available immediately for off-label use in DIPG. This will result in faster transition from bench to bed-side.
TELL US ABOUT MEFLOQUINE AND THE BLOOD-BRAIN BARRIER (BBB)
Getting drugs across the BBB to treat brain tumors in general and DIPG in particular is a big challenge. Fortunately, Mefloquine is known to cross that barrier and accumulate in the human brain. So this is a big advantage in potential DIPG treatment.
WHAT ARE THE SPECIFIC GOALS OF THIS RESEARCH BEING FUNDED BY THE CURE STARTS NOW AND DIPG COLLABORATIVE?
We will demonstrate that Mefloquine can cross the BBB, achieve the desired concentrations in the pons, halt tumor growth, and prolong survival in DIPG mouse models. These results should be sufficient to move to clinical trial with children diagnosed with DIPG.
HOW WILL YOU KNOW IF THE DRUG IS WORKING?
We are using technologies to simply light-up the DIPG tumor just like the firefly, and depending on the amount of light captured by the camera, we can see whether or not the drug is working. Basically, the less light output, the better benefit. These results are then confirmed ex vivo by removing the mice brains and looking for the tumor.
HOW WILL YOUR WORK BUILD ON PREVIOUS DIPG RESEARCH?
Our work will take advantage of DIPG cell lines and mouse models that have been developed by other leading researchers in the DIPG field. Collaborating with the broader DIPG research community will move the whole field forward more quickly.
WHY IS SUPPORT BY THE DIPG COLLABORATIVE AND THE CURE STARTS NOW IMPORTANT FOR YOUR WORK?
It is typically difficult to get federal funding for drug re-purposing. The DIPG collaborative and the Cure Starts Now will allow us to test this drug in a clinically-relevant mouse models of DIPG, and if proved successful, it can be easily translated to patients.
Researcher Spotlight: Dr. Adam Green from University of Colorado - Anschutz Medical Campus
January 4, 2018
Jesse Shumaker - Nebraska Chapter Director
Recently I met with Dr. Adam Green, a pediatric neuro-oncologist who leads a lab at the University of Colorado Cancer Center, to notify him that his grant request had been funded. Dr. Green provided background about his team and their upcoming research. Dr. Green became a DIPG investigator because he saw how DIPG is so different than other pediatric cancers due to the devastating outcome and unmet need for effective treatment. His lab searches for weaknesses in high grade gliomas such as DIPG and then explores ways to exploit those weaknesses. Dr. Green’s team has used steadily improving mouse models to try different treatments and determine what would be the most promising options to offer in clinical trials. Dr. Green and his team have brought some of these new ideas into clinical trials.
When Dr. Green attended the most recent DIPG Symposium in May of 2017, he was encouraged to hear from other researchers about progress towards control of the DIPG tumor within the brainstem, particularly by administering chemotherapy via Convection Enhanced Delivery (CED), which uses a pressurized catheter to bypass the blood brain barrier and inject the agent directly into the brainstem. While this delivery mechanism is starting to show promise for local treatment of the tumor, the most recent DIPG Symposium featured more discussion about the next concern, which is spreading of the tumor to other areas of the brain. The presentations by other researchers as well as subsequent conversations at the conference, spurred ideas that laid the groundwork for the upcoming research at Dr. Green’s lab.
One area of upcoming research at Dr. Green’s lab is the comparison of the concentrations of chemotherapy in the brain stem when administered via CED compared to oral or intravenous delivery. There are many agents that have showed promise when used against DIPG cells in the lab, but have failed to succeed in clinical trials. The aim of this research is to determine whether the problem may be at least in part due to failure of certain drugs to bypass the blood brain barrier and get to the tumor in the brain stem. This may vary depending on the type of drug and its ability to cross the blood brain barrier. This research will be performed in both mouse models and as well as through a clinical trial so it will be possible to determine how well the mouse models reflect the activity in humans.
Another aim of research is to measure the impact of the addition of craniospinal radiation in conjunction with focal radiation of the tumor. We know that radiation focused on the brainstem can be effective for a period of time, but it is not curative. As treatment of DIPG within the brainstem becomes more effective, prevention of metastasis to other areas of the brain and spine becomes a larger concern. Dr. Green’s lab will use mouse models to measure how craniospinal radiation may prevent or reduce spread of the tumor outside of the brain stem.
The goal with all of this research is to work towards a clinical trial that brings together multiple well justified treatment modalities to produce consistent, effective, and durable results for children battling DIPG.
The Cure Starts Now Foundation funds over $4 million in pediatric cancer research
January 3, 2018
Readers' Forum, Dec. 30, 2017: Fighting cancer, finding cures
December 30, 2017
Terre Haute Tribune Star
Meet Our Friend And Hero, Carson
December 29, 2017
Carson Hall was born in January 2012 and is the first born son to his parents. Carson loves to be active! He loves swimming in the summer, playing water balloons, playing on his swing set and most of all playing with his brother, Colton. He enjoys going to school and visiting the zoo – what little boy wouldn’t! Around the age of one, he began having respiratory issues, which were diagnosed as Viral Induced Asthma. However, he was otherwise healthy. He was meeting every milestone and was an extremely happy and loving child. There was no inclination that anything was, or ever would be, wrong with him.
In April of 2016, his parents started noticing changes in Carson. His behavior was different, his gait was off and he seemed dizzy a lot of the time. After weeks of persistent doctor’s appointments and phone calls, his behavior warranted a trip to the Emergency Room. The ER doctor did not realize the severity of the symptoms he was showing and told his mother that nothing was wrong, other than possible vertigo. Fortunately, the ER trip expedited a neurology appointment. On May 11, 2016 he saw a neurologist that was concerned and ordered an MRI as soon as possible. May 12, 2016 Carson’s family received the devastating news that Carson had an inoperable tumor on his brainstem, which is almost always fatal. He had, on average, 9 months to live.
“We made an appointment for a second opinion because as parents you can’t believe someone is telling you that your child will not make it,” said Lindsay, Carson’s mom.
On May 13, 2016 the Halls learned the name of the tumor was Diffuse Intrinsic Pontine Glioma, DIPG, and the prognosis was indeed correct. Carson received the standard 30 days of radiation therapy, which was completed in July of 2016. Prior to radiation, he was unable to walk or feed himself and was also very hard to understand. Shortly after radiation, besides the side effects from the steroids, you would not know anything was wrong with him. His tumor shrank an amazing 50% and he was back to himself!
In February 2017, a routine follow up MRI showed tumor progression. At this point he was not showing any symptoms, but his family was told they would see them in approximately 6 weeks. The doctor was spot on. They started noticing increased symptoms about 6 weeks later. The Halls contacted Carson’s doctors and came to an agreement to do re-irradiation. Carson is now 17 months past diagnosis and is 100% a normal 5-year-old boy. He runs and jumps and plays. The best thing post-diagnosis that his family has done to make memories is to travel. His Make A Wish trip was a Disney Cruise and they have traveled to Mexico to go to the beach, one of his favorite things to do! He lost his first tooth and he started Kindergarten, both things they never thought they would get to experience with their son.
Carson’s mother says, “Although our future is unknown, we are choosing to live each day to the fullest. We are busy making memories that will last a lifetime no matter what our future brings. What we do know, however, is that childhood cancer is extremely underfunded. DIPG is unknown to most people. We need to raise awareness. We need to increase funding. Most of all, we need a cure. We have to continue to work together to advocate for our kids and continue to spread awareness. Not just for DIPG, but for all pediatric cancers.”
Researcher Spotlight: Dr. Maria Tsoli from Lowy Cancer Research Centre
December 27, 2017
A senior scientist at Lowy Cancer Research Centre, Dr. Maria Tsoli is helping to lead the charge to focus on the deadly disease of DIPG in Australia. Dr. Tsoli is the recipient of over $225,000 in research grants from The Cure Starts Now and our DIPG Collaborative partners.
“The CSN funding has been pivotal in establishing our DIPG Research Program at the Children’s Cancer Institute. This is the first established laboratory in Australia with a program specifically focused on developing novel treatments for DIPG. Each grant received has allowed the program to explore diverse therapeutic approaches and generate preliminary data to attract additional funding from larger national grant schemes. More importantly it has led to one of our recent discoveries (CBL0137)—shown to have promising therapeutic efficacy in DIPG preclinical models — to be developed as a COG Phase 1 trial.
We should expect a plethora of new therapeutic approaches to be introduced and trialed over the next five years. These include biotherapeutics, antibodies, immunotherapies, sequential drug treatments, as well as new methods to overcome the blood-brain-barrier. I would like to thank the donors and those involved in securing funding for our lab and other teams globally.
Without funding we would not be able to develop pre-clinical models of DIPG, examine the therapeutic efficacy of drugs and understand the biology of this tumour.”
Researcher Spotlight: Dr. Maryam Fouladi and Dr. Rachid Drissi from Cincinnati Children's Hospital Medical Center
December 15, 2017
Lynn Whittington - Indiana Chapter of The Cure Starts Now
With nearly everything we do in life whether it is in business, sports, or even (if you are like me) everyday activities such as grocery shopping, we have to have strategies. (Yes, I really do have a strategy shopping for my milk and eggs at the grocery store but we don’t need to get into that). A better example is, if you are a coach of a football team, you don’t send your players out on the field without a strategy or you risk the chance losing the game; or worse someone will get hurt! Additionally, you wouldn’t use the same exact play every time you send your team out onto the field. That being said, Doctor Maryam Fouladi, a leading pediatric brain cancer oncologist at Cincinnati Children’s Hospital, has created a new and very effective strategy to add to our playbook of “The Homerun Cure”(Okay, maybe I should’ve used a baseball analogy instead of football, but I’m pretty sure you know what I mean). Fouladi’s project is called CONNECT (Collaborative Network of Neuro-Oncology Clinical Trials) Collaborative. It is essentially a network of neuro-oncology clinical trials performed at international sites by the world’s leaders in childhood brain cancer research and it was built on the network that was created by the DIPG Registry. You might even look at it as a virtual hospital for pediatric brain cancers.
I had the opportunity to meet with Dr. Fouladi and her colleague, Dr. Drissi, to discuss this exciting new collaborative as well as an upcoming trial. Fouladi very openly explained that the main goal of CONNECT Collaborative is to provide as many places for children with DIPG and other high grade gliomas to go for treatment. She reached out to 16 different institutions, who have all been partners in the past and know that they work very well together as they have the same mission. And each of them was enthusiastic and more than willing to come on board to find better and MORE treatment options, which will eventually lead to that homerun cure we so desperately need. The list of institutions participating is as follows: Baylor College of Medicine (USA), Children’s Nat’l Med Center (USA), Dana Farber Cancer Center (USA), Seattle Children’s(USA), Lurie Children’s (USA), Children’s Hospital of Colorado (USA), Great Ormond Street Hospital (UK),German Cancer Research Center (Germany), VU University Med Center (Netherlands), Hospital for Sick Children (Canada), Montreal Children’s (Canada), Lady Cilento Children’s ( Australia), Princess Margaret Hospital for Children ( Australia), Sydney Children’s (Australia), and McMaster Children’s (Canada), with Cincinnati Children’s (USA) as the lead operations center. It is important to point out that ALL of the sites involved are equal partners and can open all studies in the CONNECT Collaborative and can contribute new ideas for these trials. The doctors from each of these chosen institutions carry so much clout from the work they have done, that it has been significantly easier to get drug companies on board, thus far. That alone is a HUGE feat!
Currently there are clinical trials for patients with recurrent tumors and much larger trials through bigger consortia for newly-diagnosed patients as well as recurring patients. However, there is a huge gap in the middle where smaller feasibility studies NEED to be conducted in newly-diagnosed patients to see if the new treatment regimen being considered for much larger trials is tolerable and safe in order to push forward to larger studies. This will give families more hope and encouragement as now they will have more studies available to take part in. The CONNECT Collaborative bridges that gap between the newly-diagnosed and recurring patients.
With this new strategy, we will have better geographical options for families with kids who are in the fight. One of the goals is to make it so a family doesn’t have to pick up and temporarily move to a different country in order to have their child participate in a study. This alone eliminates a large portion of stress and fear these families face. Let alone the financial burden of traveling out of their own countries.
We are basically waging a war against DIPG and other high grade gliomas. And it is a World War. We need allies in other countries to come together, learn about the enemy (brain bancer) and defeat it! So by creating this connection between some of the world’s leading pediatric brain cancer researchers, we can effectively and efficiently speed up the process of achieving more accurate results! This also eliminates the possibility of repeating trials which is a waste of time and money. Additionally, advances in the trials will be made much faster! As we all know, time is of the essence with many of these brain cancers.
After speaking with Dr. Fouladi about what exactly the “CONNECT Collaborative” is, I learned the exciting news that Dr. Dewire and Dr. Drissi are beginning the first two studies for the CONNECT Collaborative! Dr. Dewire’s RAD001 and LEE011 study (previously funded by The Cure Starts Now) being the first and is currently taking enrollment. Dr. Drissi’s BMI-1 inhibitor study will be the second and is expected to begin hopefully in January or February. The protocol has been written, the drug company is on board and soon the doctors will send the proposal to the FDA for approval of this study.
What is BMI-1? BMI-1 is a protein found in cells of a normal brain. However, this particular protein is highly expressed in DIPG. Meaning there is significantly more BMI-1 proteins in the tumor cells than found in normal brain cells. While normal cells NEED controlled levels of BMI-1, in DIPG the levels are 2-26-folds higher. Anytime there is something abnormally high in a tumor that means the tumor probably NEEDS whatever it is to grow and survive.
When Dr. Drisssi looked back at published studies performed on tumor tissues, he noticed BMI-1 was highly expressed in all DIPG tumors. This was a very exciting find because this could mean that the protein could be a therapeutic target for the researchers to decrease which would then slow the tumor growth.
So once he knew BMI-1 is highly expressed in DIPG (and other cancers for that matter), his next step was to test living DIPG tumor cells that parents, like me and so many others have donated through autopsy. Drissi wanted to find out what drug could affect or inhibit the growth of BMI-1 levels. And guess what?! He found one! Even better, it is now in clinical trials for adults! However, it is not yet commercially available. Meaning it hadn’t been tested enough to assess its efficacy nor has it had safety studies in pediatrics. Therefore, he could only use it in the lab. When Dr. Drissi did use this inhibitor on living DIPG tumor cells he was incredibly surprised to learn that it did in fact kill a large portion of these tumor cells. DIPG has 3 sub-types and the BMI-1 inhibitor works on ALL of them!
Could this mean that BMI-1 is the mother ship or the driver of DIPG cancer cells and many other cancer cells? Now that we know BMI-1 protein plays such a huge role in these tumors and we found an inhibitor that can actually kill many of these cells, doctors need to figure out a safe way to use it to treat children. Amazingly enough, Dr. Drissi found another study currently taking place on adults. Remember, that BMI-1 is found in other cancers, not just DIPG. From the results of the adult studies we now know how to give the drug and what doses are safe, at least in adults. All very exciting! Even MORE exciting, the scientists who are conducting the adult studies were/are extremely willing to cooperate with Dr. Drissi as they understand the importance of advancing pediatric cancer treatments by making this inhibitor available for children.
One of the goals of Dr. Drissi’s new study is to lower levels of BMI-1, not completely get rid of it. As mentioned before, the normal brain needs some levels of this protein. So with this new inhibitor it will reduce the BMI-1 levels, making DIPG cells incredibly sensitive to therapies. We know that radiation shrinks DIPG tumors and we also know that the BMI-1 inhibitor makes DIPG cells more sensitive to radiation. Dr. Drissi’s study is to incorporate both radiation and the BMI-1 inhibitor making radiation more effective which may then sustain the lives of these precious children. This inhibitor also allows for potential reduction in radiation therapy doses. Let’s face it; we all have a love/hate relationship with radiation. And if the radiation dose doesn’t always get reduced it will at least be more effective than it is today.
Now a good question is: How do you safely deliver this drug? Most of us know getting past the Blood Bain Barrier has been a pretty difficult and frustrating issue. Well, I’m excited to share with you that there is some data showing that this particular inhibitor actually does cross that barrier! However, the proof will be in the upcoming study.
Sustaining a child’s life, but also allowing them to maintain quality of life is one of the major goals of this study and other studies in the CONNECT Collaborative. Most of us know that the average survival rate of kids with DIPG is only about 8-9 months. If we can push that for ALL or even MOST of these children to be over a year or a year and a half, then that alone is success. However, the ultimate goal through the CONNECT Collaborative using studies like Dr. Drissi’s upcoming BMI-1 inhibitor trial is to cure this disease. Until now, researchers have been making incremental steps and that just isn’t enough anymore.
And because of all of the hard work and generosity from the families who pushed for autopsies so they could donate their child’s tumor for research, The Cure Starts Now and chapters, foundations who are a part of the DIPG Collaborative, as well as every single advocate, business sponsorship, fundraising partner, and donor; in the last five years researchers have learned more about DIPG than they had in the fifty years prior! With all of the funding from all of the parties mentioned above, along with new forward thinking strategies like CONNECT Collaborative; I personally believe without a shadow of a doubt that a cure for DIPG and other high grade gliomas will happen much sooner than later, which will then finally lead us to the HOMERUN CURE FOR ALL CANCER! And when that day comes I will personally fund one last Carnival for the Cure (a fundraising event I do every June in Columbus, Indiana for childhood brain cancer research) which will require ZERO sponsors, ZERO dollars and will be FREE for all. And on that day we will join together in celebration of all of the beautiful children who have gone before us so that others will get the chance to live. That day will be the absolute BEST DAY EVER!
Researcher Spotlight: Dr. Mariella Filbin from the Dana-Farber Cancer Institute
December 12, 2017
Where are you from? Where did you study?
I am from Austria. I received my Medical Degree from the University of Graz in Austria, and my PhD from the University of Vienna. I came to Boston where I did my Residency in Pediatrics and Fellowship for Pediatric Hematology/Oncology at Dana-Farber Boston Children’s.
When and why did you decide to research DIPG?
My journey with Neuro-Oncology started in Austria over 15 years ago when I was 21 yrs old. I was exposed to patients right away, and one of the first pediatric patients was a girl diagnosed with DIPG that was getting radiation. I started asking questions about DIPG, and was shocked to hear there were no treatment options. I was an enthusiastic med student, so I kept searching and still kept finding no additional treatment for children with DIPG.
How is the research you are currently doing different than other DIPG research?
Currently most researchers receive frozen biopsy tissue of patients in Boston or other hospitals. Researchers then grind up the samples into a “soup”, which is a mixture of all cells. Once in the soup, we can’t separate the cells back apart.
With this new grant, I will partner directly with hospitals to get fresh biopsy tissue samples and then immediately split the tissue into single cells. Each single cell will then be separately analyzed for their genetic profile.
This type of biopsy will allow for much more information to be gained by having separated single cells. This will also allow us to ask many questions. Are the tumor cells all the same or different? Are there immune cells and if so which ones? Are there any other cells that are supporting the tumor?
What are the implications if this protocol is successful?
What I have already found out is there is a hierarchy within the tumor of really bad cells called “cancer stem cells.” These are the only ones dividing. My hope is to develop a new way of therapy, called Differentiation Therapy. The idea is to push cancer cells from the bad cancer state to a more mature state. The drugs in essence would tell them to stop doing what they are doing, to remember what they were supposed to do, and to be more like a “normal” cell.
Is this part of a large protocol?
Yes and No. I started on biopsies in Boston only and have since then expanded to my old team in Vienna, Austria, and now San Francisco. I’m headed to a conference in San Francisco to see if more Doctors want to join efforts.
Where did you get the idea to focus on this protocol?
I wanted to look at new ways to analyze DIPG tumors. I went to a seminar at MIT, one of the best Technology Universities, where engineers talked about single cell technology.
I thought if we could use this cool new technology for DIPG, we could learn so much more. Everybody I approached said it was not possible. I insisted, and it has taken 2 ½ years to show others that we can use this technology. And, it’s running really well.
Why is support by the DIPG Collaborative and The Cure Starts Now important for this?
This is New Technology, so it’s deemed a high-risk project, in addition to being research on a rare tumor. The DIPG Collaborative and The Cure Starts Now allow me the funding to generate data to then go back to the government and say it’s feasible & to fund more DIPG research.