Research

Studies supported by Credit Unions Kids at Heart demonstrate for the first time that enhancing the clearance of brain tumor cells debris via “protectins” and “resolvins” is a novel biological target to prevent brain cancer in the future. Also stimulating the resolution of inflammation prevents cancer progression. A high omega-3 fatty acid diet can improve immunotherapy to block cancer in several models. Studies involve targeting certain pro-inflammatory lipid pathway enzymes in combination with chemotherapy and immunotherapy prevents different types of cancer. These “pro-resolving” therapies are a unique approach to turning off inflammation in cancer and will be evaluated in upcoming clinical cancer trials including brain, pancreatic, and colorectal cancers. These promising discoveries will soon lead to new therapeutic approaches to the treatment of children and adults diagnosed with brain tumors, and one day, the prevention of pediatric brain cancers.

*Credit Unions Kids at Heart established the CJ Buckley Memorial Fund in 2019 for Pediatric Brain Cancer Research to support the groundbreaking work of the Panigrahy Lab at Beth Israel Deaconess Medical Center. Dr. Dipak Panigrahy, principal research investigator, and his team study the impact of inflammation on cancer in the hope of stopping the growth of cancerous cells. CU Kids at Heart raises money for this fund through corporate and private donations, not through its Boston Marathon fundraising activities.

With the ongoing support of the Credit Unions Kids at Heart team, Dr. Stone and his team are uncovering the causes of epilepsy in children burdened by unrelenting seizures. The result? Targeted therapies that can halt seizures and enable children to live full and healthy lives. Dr. Stone and his team have designed and refined customized electrodes that can record activity at an individual neuron level. These electrodes enable specialists to understand how epilepsy develops—and where it originates—down to a single cell. It’s equivalent to putting a microphone on every single person in a crowd rather than recording populations of people at once. Dr. Stone implanted electrodes in the study’s first few patients this fall and expected to enroll 20 to 30 patients a year in the study. In addition, the data from the electrodes will also help experts learn about the biology of epilepsy to design and test new treatments.

Bringing in the power of Genetics

Dr. Stone and his team also are extracting DNA from the research and standard electrodes after they are removed to build a brain-wide map of genetic alterations. These alterations may be specific to one location in the brain but not another. This data can help explain, for example, why seizures start in one part of the brain in one patient and not another. Dr. Stone is collaborating with a genetics research fellow (a neurosurgical resident from UCLA) and experts in the Epilepsy Genetics Program at Boston Children’s to uncover unknown causes of epilepsy and change life trajectories.

Epilepsy in children differs from epilepsy in adults in important ways. Young children are progressing through critical developmental stages, and seizures can disrupt that development. If missed, it can be very difficult to get caught up—impacting children for a lifetime.

~Dr. Scellig Stone, MD, PhD

*This research at Boston Children’s Hospital is supported by the CU Kids at Heart Boston Marathon fundraising.

Dr. Smith and his colleagues published the successful results of a series of procedures performed using a surgical technique that they developed to treat a rare subset of moyamoya patients. The new technique—Pial Pericranial Dural (PiPeD) revascularization—builds on the principles of pial synangiosis, a revolutionary surgical treatment introduced at Boston Children’s that is now the gold standard of surgical care for moyamoya. In addition to further advancing surgical treatment for moyamoya, Dr. Smith and his team are also making inroads into how the disease can be diagnosed and monitored. Early identification of moyamoya—before disabling stroke occurs—has been a challenge due to the lack of easy, effective methods of detection. This year, Dr. Smith and his colleagues reported, for the first time, a panel of urinary biomarkers that predicts the presence of moyamoya.

Guidelines impact care worldwide

Dr. Smith continues his role as an international leader in setting new standards of care for patients with cerebrovascular disease. Serving on the board of directors of the International Pediatric Stroke Organization (IPSO), he led the development of moyamoya guidelines that were formally accepted by the organization’s Neurology Working Group—representing the largest group of stroke neurologists in the world. Dr. Smith’s leadership with the IPSO is just one example of how his work is impacting care worldwide. Since the American Heart Association (AHA) introduced new protocols incorporating Dr. Smith’s radiographic biomarkers in the diagnosis of cerebrovascular disease and identification of stroke risk among newborns and children with moyamoya, there has been a dramatic 42% reduction in perioperative stroke.

*This research at Boston Children’s Hospital is supported by the CU Kids at Heart Boston Marathon fundraising.

Dr. Panigrahy and his team are developing medicines to block a naturally occurring medical phenomenon called a "cytokine storm." A cytokine storm is an excessive immune response common to infections and autoimmune disorders that can cause dangerous levels of inflammation in the body. In studies done in collaboration with Professors Charles Serhan of Brigham & Women’s Hospital and Bruce Hammock of University of California-Davis, the team in the Panigrahy lab have shown that cell debris from surgery, chemotherapy, toxin exposure and other causes can lead to production of high levels of these pro-inflammatory mediators called cytokines. Their novel approach to inflammation resolution in studies of cancer and other illnesses has been shown to prevent cytokine storm. COVID-19 patients can experience lethal levels of inflammation of lung and other organ tissues also caused by a cytokine storm. These researchers believe that their treatments may work in COVID-19 patients and in children suffering from the multi-system inflammatory syndrome that appears to be associated with COVID-19 just as the drugs developed by this team, now in clinical trials, have worked to treat patients with other illnesses. These scientists hope to begin clinical trials for new COVID-19 treatments within the coming months and are currently pursuing partnerships and funding opportunities.

*CU Kids at Heart founded the CJ Buckley Memorial Fund for Pediatric Brain Cancer Research at Beth Israel Deaconess Medical Center to support the work of the Panigrahy Lab. CU Kids at Heart raises money for this fund through corporate and private donations, not through its Boston Marathon fundraising activities. This new 2020 COVID-19 research is a direct result of studies conducted by this Lab and supported by CU Kids at Heart; see “Study of Simulation of Resolution of Inflammation in Cancer” for more information.

Surgeon-scientist Dr. Stone, with his team at Boston Children’s Hospital, has spearheaded a surgical technique called “Stereoelectroencephalography,” or “SEEG”, for epilepsy and seizure disorders which allows for extremely precise, targeted analysis of brain activity. In a less-invasive surgical procedure than many typical brain surgeries, these electrodes and sensors are placed in a child’s brain for a period of time to document seizure activity and pinpoint its source. Only then is additional surgery performed to remove the seizure-causing tissue. Dr. Stone seeks to improve and advance these minimally invasive techniques to minimize recurrences of seizures and encourage functional regeneration and repair of the brain. His research plans include the further clinical testing of custom micro-wires that record seizure activity from even an individual neuron, or brain cell.

*This research at Boston Children’s Hospital is supported by the CU Kids at Heart Boston Marathon fundraising.

Moyamoya disease is a rare, neurovascular condition in which the walls of the vessels that supply blood to the brain become thickened and narrowed resulting in a reduction of blood flow. This blockage puts patients at risk of transient ischemic attacks (TIAs) and strokes. Dr. Smith and his team—international leaders in understanding and treating this disease—seek to develop novel, noninvasive methods to better evaluate the blood flow in the brain of Moyamoya patients. The underlying goal of this research is to better determine which patients may be candidates for surgery and to improve the team's ability to assess the success of surgical revascularization after treatment. This work is being done by a multidisciplinary team of surgeons, radiologists, and interventionalists.

*This research at Boston Children’s Hospital is supported by the CU Kids at Heart Boston Marathon fundraising.

Increasingly, medical investigators are recognizing that Moyamoya is not just one disease or disorder, but is actually a group of many different conditions that seem to share a common end-pathway with vessel narrowing and stroke. Discovering the genes and mutations that may be associated with Moyamoya is critically important both to determine a prognosis in newly diagnosed patients and to help inform potential future treatments. In this multi-center study, Dr. Smith and his team aim to discover unique genetic causes of Moyamoya that can improve clinical diagnosis, prognosis, and therapy.

*This research at Boston Children’s Hospital is supported by the CU Kids at Heart Boston Marathon fundraising.

A longstanding method to evaluate how well a pediatric patient's Moyamoya surgery worked is to perform a catheter angiogram. While these tests provided a great amount of detail and are necessary before surgery (as learned, in part, from research previously funded by Credit Unions Kids at Heart and now incorporated into national guidelines), improvements in other imaging modalities have now called into question whether the use of catheter angiograms can be reduced in postoperative patients. This study seeks to determine which subset of patients still benefits from catheter angiograms post-surgery, with the goal of reducing the number of post-surgery catheter angiograms overall.

*This research at Boston Children’s Hospital is supported by the CU Kids at Heart Boston Marathon fundraising

One of the primary problems in cerebral palsy and other conditions that relate to brain injury from previous stroke is the inability of the brain to recruit a new blood supply to help with healing an old injury or maximizing recovery of brain near the injury in tissue that remains alive but is unable to work at full capacity due to limited blood supply at the penumbra (stroke edge). This problem is particularly relevant to children with cerebral palsy, as they have had some form of brain injury early in life, but, unlike adults, have a growing brain that may require increasing recruitment of blood supply over time. In this study, Dr. Smith and his team are investigating the molecule netrin-1 as a driver of brain endothelial cell migration, invasion and tube formation specifically in the setting of low oxygen (hypoxia), to mimic the environment of the brain in patients with cerebral palsy. They aim to discover how to better engineer new blood supply to the brain in the hope of maximizing recovery and improving therapeutic response in patients with cerebral palsy.

*This research at Boston Children’s Hospital is supported by the CU Kids at Heart Boston Marathon fundraising.

Recent research shows that radiation and chemotherapy, both standard treatments for most cancers, leave behind dying cancer cells, or "cellular debris." Over the past year, Dr. Panigrahy and his team have demonstrated that during the course of these treatments, the cellular debris can actually trigger tumor-promoting inflammation and the growth of microscopic cancer cells. Their studies show that these traditional cancer treatments are a "double-edged sword"—the very treatment used to cure the cancer is, in fact, also helping it survive. Dr. Panigrahy and his team believe that this cancer growth could be prevented by stimulating the body's naturally-occurring molecules to intervene and "resolve" the inflammation. Their methods to enhance the resolvin pathways are currently in clinical trials for inflammatory diseases, and in the 2019-2020 year, will turn their focus their research on the use of this type of approach for pediatric brain tumors and other cancers. Additionally, this year this team will study pro-resolution lipids called protectins as a way to prevent and treat medulloblastoma, glioblastoma, and other brain cancers via stimulation of resolution of inflammation as well as the combination of resolvins and immunotherapy to synergistically inhibit cancer. This coming year, the Panigrahy laboratory will investigate new pro-resolution lipids called maresins to prevent experimental cancer by clearing tumor debris. “Debris” from non-tumorigenic cells, such as blood vessels and immune cells, generated by steroids, cyclosporine, statins, tamoxifen, or chemotherapy can paradoxically stimulate tumor growth that can be blocked by maresins. These findings also provide new information on why these drugs can increase a patient’s risk of cancer.

*CU Kids at Heart founded the CJ Buckley Memorial Fund for Pediatric Brain Cancer Research at Beth Israel Deaconess Medical Center to support the work of the Panigrahy Lab. CU Kids at Heart raises money for this fund through corporate and private donations, not through its Boston Marathon fundraising activities.