Cancer Moonshot Yields Data-Sharing Initiatives, Hemophilia Surprise, Mitochondrial Medal

Buckle your seatbelts because this has been a busy week for research news at Children’s Hospital of Philadelphia. (It was also Teen Driver Safety Week, a topic we touched on with one of our blog posts earlier this week and in last week’s In the News post.) Cancer research is hitting the accelerator with the release of the national Cancer Moonshot Initiative’s final report to the President — and two CHOP-involved initiatives announced their commitments to the Moonshot’s call to action. CHOP hemophilia researchers took a look under the hood of how cells respond to protein infusions to treat this bleeding disorder, finding that one key protein behaved in the exact opposite way it was expected to. And look both ways for what might be some shiny chrome speeding our way in the form of the 2017 Franklin Medal. The recipient of this prestigious award in life sciences was announced this week to be a CHOP scientist who is world renowned as the founder of the field of mitochondrial medicine. Check out more on all of these stories below.

CHOP-Involved Commitments Announced With Cancer Moonshot Final Report

If the name “Cavatica” sounds familiar, you might remember it as the surname of a helpful spider named Charlotte in E.B. White’s classic book “Charlotte’s Web.” Now a new CAVATICA is spinning a web to connect and help people with computing tools for research on cancer and other rare diseases. This CAVATICA is a cloud-based biomedical data analysis platform created by the Children's Brain Tumor Tissue Consortium (CBTTC), whose operations center is located at CHOP, with the Pacific Pediatric Neuro-Oncology Consortium, in partnership with Seven Bridges Genomics.

"CAVATICA gives us an unprecedented opportunity to research a number of childhood diseases, ranging from pediatric brain tumors that are the leading cause of disease-related death in children to rare pediatric disorders that get limited attention and resources," said Adam Resnick, PhD, an expert in brain tumors and director of the Center for Data-Driven Discovery in Biomedicine at CHOP.

By making large volumes of genomic and other types of data from multiple diseases available within the context of tools to share and analyze that data, CAVATICA is answering the Cancer Moonshot's call to share data and make it more useful to accelerate progress against pediatric cancer and other diseases.

Dr. Resnick and collaborators from CBTTC, PNOC, and Seven Bridges attended the White House Cancer Moonshot report release event Oct. 17 and shared the launch of CAVATICA among the commitments announced in response to Vice President Biden’s call to action.

Another CHOP-involved initiative was also announced among the commitments responding to that call to action: CHOP is one of 12 medical research centers partnering with the nonprofit Open Commons Consortium to build a pilot biomedical data commons, the Contribute & Change (C2) Cancer Commons, and a pilot platform where multiple systems connect to share cancer data, the Cancer Commons Hub. These tools aim to dramatically increase the amount of data available to researchers to fuel improvements in cancer outcomes.

Read more about the Cancer Moonshot report and all of the announced commitments in the White House fact sheet.

Finding Suggests ‘Less is More’ Approach in New Hemophilia A Treatments

Hematology researchers have found that blocking the role of a common protein may offer unexpected benefits for patients with the inherited disorder hemophilia A, the most common form of the condition hemophilia in which patients are unable to control bleeding.

The new research, done in cells and animals, contradicts prevailing assumptions about the biological effect of a protein called furin, an important enzyme found in most cells. The scientists report that, although furin improves blood clotting in hemophilia B (the other common form of hemophilia), in hemophilia A, the protein impairs clotting instead — the opposite effect.

Doctors treat either form of hemophilia with intravenous transfusions of proteins to replace a missing clotting factor, which differs depending on the type of hemophilia. Those replacement drugs also contain amino acids that recognize and interact with furin, but the new research calls that into question.

“We were surprised to find no evidence that furin was required in factor VIII replacement [for hemophilia A], as it is in factor IX [for hemophilia B],” said study leader Valder R. Arruda, MD, PhD, a hematology researcher at CHOP.

This discovery may trigger a reassessment in hemophilia research, including research into gene therapy approaches.

“In gene therapy, size matters,” Dr. Arruda said. “It’s important to reduce the gene package for FVIII to the smallest effective size.” He added that deleting the furin-recognition components both decreases the size of the gene therapy payload and strengthens its benefits for treating hemophilia A.

The researchers also bioengineered a new variant protein, FVIII-∆F, which avoids interacting with furin. In mice treated in gene therapy experiments, the variant increased FVIII levels and improved clotting activity.

Dr. Arruda and colleagues from CHOP, Penn Medicine, and the University of North Carolina, Chapel Hill (UNC) co-authored the study appearing this week in the journal JCI Insight.

Douglas Wallace Selected for Prestigious Franklin Medal in Life Science

The Franklin Institute announced this week that it has selected Douglas Wallace, PhD, founder and director of the Center for Mitochondrial and Epigenomic Medicine at CHOP, as the recipient of the 2017 Benjamin Franklin Medal in Life Science. This highly esteemed international award, established in 1824, has been awarded to scientific luminaries including Albert Einstein, Thomas Edison, Stephen Hawking, Marie Curie, Nikola Tesla, Niels Bohr, Bill Gates, and Max Planck. More than 100 Franklin Medal laureates have also received Nobel Prizes.

Dr. Wallace has achieved worldwide prominence as the founder of mitochondrial medicine. During the 1970s, Dr. Wallace defined the genetics of the DNA located in the mitochondria, the “power plants” of the cell, including demonstrating that human mitochondrial DNA is exclusively maternally inherited. Applying this fact to the study of human evolution, Dr. Wallace reconstructed the origins and ancient migrations of humans out of Africa and around the world. In the realm of human health, analysis of the mitochondrial DNAs of a diverse array of patients led Dr. Wallace to discover mitochondrial DNA diseases and that mitochondrial DNA variation contributes to a wide range of rare and common metabolic and degenerative diseases as well as cancer and aging. His program is an important part of our newly launched Roberts Collaborative for Genetics and Individualized Medicine.

Earlier this year, Dr. Wallace received another prestigious honor with his induction as one of only 75 foreign members of the Italian Academy of Sciences.

Read more about Dr. Wallace, mitochondrial medicine, and the other 2017 Franklin Medal winners, in the Philadelphia Inquirer.

ICYMI

In case you missed it earlier this week on Cornerstone, our Chief Scientific Officer Bryan A. Wolf, MD, PhD, interviewed pediatric oncologist Peter Adamson, MD, about the Cancer Moonshot; and for Teen Driver Safety Week, we shared research that aims to reduce distracted driving among teenagers and their parents.

Last week’s chock-full In the News post featured a study showing that teens mostly do adhere to Graduated Driver Licensing rules; a look back at a study of school nutrition laws and their potential impact on obesity; an autism expert sharing her knowledge with peers in Dubai; work that identified inadequate pregnancy screening for teen girls with cancer; and a perspective on the importance of pediatric research to ensure the effectiveness and safety of drugs for children.

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