Team Science, CAROL Funding, Circadian Rhythms, Spinal Muscular Atrophy

 

Cheer on an interdisciplinary, global team of researchers led by Yael Mossé, MD, as they enter the final round of Cancer Grand Challenges, in our Children's Hospital of Philadelphia news roundup this week. A collaborative team studying mitral valve disease receives CAROL funding to continue their work, a CHOP physician scientist shares her expertise in an NHLBI workshop on circadian research, and an interview highlights progress of spinal muscular atrophy treatments being studied at CHOP.

Team KOODAC Among 12 Cancer Grand Challenges Finalists

Team KOODAC, an interdisciplinary, global team of researchers led by Yael Mossé, MD, attending physician in the Cancer Center at CHOP, has been selected as one of 12 teams shortlisted for the final stages of Cancer Grand Challenges. Now, her team will receive seed funding to draft a full research proposal and compete for up to $25 million in funding for their project.

"I am humbled and incredibly energized to be one step closer to leading a team with outstanding and broad expertise, who together will develop drugs that we intend to become the new standard of care for children with solid malignancies," Dr. Mossé said.

If successful, team KOODAC, comprised of scientists from the United States, Austria, France, Germany, and the United Kingdom, aims to develop drugs that break down or "degrade" five of the most significant cancer-driving proteins in children with high-risk oncogene-driven cancers, including neuroblastoma, medulloblastoma, Ewing sarcoma, fibrolamellar hepatocellular carcinoma, rhabdomyosarcoma, and other cancers that deregulate these essential oncoproteins.

Find out more in this CHOP news release.

Collaborative Program Receives CAROL Funding for Mitral Valve Disease Research

The National Heart, Lung, and Blood Institute (NHLBI) awarded a CHOP-Columbia collaborative program, "Serotonin Signaling in Mitral Valve Homeostasis, Maintenance and Restoration" – supplemental grant support from the Cardiovascular Advances in Research and Opportunities Legacy (CAROL) Act Program. Co-led by CHOP's Robert Levy, MD, and Columbia's Giovanni Ferrari, PhD, they are investigating novel directions related to heart valve leaflet biomechanics, and how these influence the progression of mitral valve disease through serotonin receptor signaling mechanisms.

Findings from a study published by the same collaborative earlier this year in Science Translational Medicine revealed that serotonin can affect the heart's mitral valve and potentially accelerate an existing cardiac condition known as degenerative mitral regurgitation. This grant will allow Dr. Levy and his colleagues to continue their mitral valve research.

The CAROL Act provides support for the innovative research that is necessary to put high risk patients on a path to living long and healthy lives. United States Congressman Andy Barr introduced this legislation to honor the legacy of his wife, Carol Leavell Barr, who died from sudden cardiac death brought on by mitral valve prolapse.

CHOP Scientist Presents Circadian Research at NHLBI Workshop

The NHLBI invited CHOP's attending neonatologist and physician scientist Shaon Sengupta, MBBS, MPH to moderate and present in a three-day virtual workshop titled "Circadian Clock at the Interface of Lung Health and Disease." Hosted by the NHLBI Sept. 14, 15, and 18, the workshop covered the application of developing advances in circadian science to priorities in lung biology, disease, and therapeutics research by stimulating multidisciplinary discussions between exceptional pulmonary and circadian investigators.

Dr. Sengupta co-moderated a session on clock biology and lung pathophysiology, and she presented her project titled "Circadian Rhythms as Therapeutic Targets in Critical Illness." Her most recent study, published in JCI Insight, showed — for the first time — that circadian rhythms contribute to lung regeneration independent of the clock's effect on inflammation.

Additionally, her team discovered lung organoids have a functional circadian clock, and the disruption of this clock impairs regenerative capacity. Poor circadian rhythms were associated with significantly higher risk of hospital admission, length of stay, and higher 30-day mortality following discharge.

Learn more about the workshop through the NHLBI.

Neurologist Finds Treatments for SMA 'Extremely Encouraging'

Interim Neuromuscular Section Head in CHOP's Division of Neurology, John Brandsema, MD, spoke with NeurologyToday about the progress of treatment for spinal muscular atrophy (SMA), a progressive, genetic neuromuscular disease that affects the motor nerve cells in the spinal cord, causing muscle wasting and weakness, eventually taking away the ability to walk, eat, and breathe. Before the Food and Drug Administration approved the first drug to treat SMA, antisense oligonucleotide nusinersen, in December of 2016, SMA was the most common genetic cause of death in infants.

"It's difficult to overstate the impact of nusinersen and the other new therapies. It's a 180-degree change," Dr. Brandsema stated. "We went from disclosing a diagnosis that had no effective treatment, supportively caring for the patient, and trying our best to augment whatever function we could in the face of a relentlessly progressive disease."

As the neurologist who diagnosed patients like Jaxon Payne with SMA, Dr. Brandsema finds the latest results of a five-year open-label phase 2 NURTURE clinical trial, which evaluated nusinersen's safety and efficacy in 25 children diagnosed with SMA as infants, "extremely encouraging."

He noted that even in the most severe infantile onset form, despite a period in which the patients rapidly change, they reach a plateau in their disease. In his own clinic, nusinersen continues to be well tolerated with no major safety concerns, and the likelihood of needing to change management is very low, demonstrating the impact this drug has had on patients' quality of life.

Check out the full article on NeurologyToday for more information.

ICYMI

Catch up on our headlines from our Sept. 1 In the News:

• Researchers Develop Inexpensive, Easy-to-Use RNA Sequencing Technique
• Citadel Credit Union Renews Commitment to Parkway Run & Walk
• Neighborhood Opportunity Linked to Pediatric Primary Care Outcomes
• CHOP Scientists Receive Doris Duke Foundation Awards
• Proof-of-Concept Study Identifies Way to Deliver Gene Editing Tools to the Brain

Keep up with our news, stories, and updates in real time by following us on Twitter, LinkedIn, or Instagram. Meet the minds behind the science in the Bench to Bedside podcast. Or subscribe to our newsletter to receive an email every other Friday by signing up here.