Promise in Precision
Affordable, quality genetic information will transform the way providers diagnose patients, develop and deliver targeted therapies, and help entire populations avoid, prevent or mitigate diseases. The degree to which investments are made in pediatric precision medicine — where it can bear the greatest impact over a lifetime — will forever alter health for generations to come.
For more on this topic, read the December 2018 editorial penned by Larry Moss, MD, Nemours President & CEO, and published by Becker’s Hospital Review.
Customizing Care, Changing Lives
The Nemours Precision Medicine program leverages genetic screening and sequencing, genomics and bioinformatics, gene therapy research and pharmaco-genetics to target specific genetic information about patients and their conditions. Together, physicians and researchers throughout Nemours are working to provide customized solutions to some of the most challenging pediatric diagnoses — and expediting those solutions from the bench to bedside. Benefits include:
- more efficient diagnoses
- more effective treatments
- fewer side effects
- reduced costs
Once the leading genetic cause of death in infants, SMA is now a treatable disease
The successful collaboration between Richard Finkel, MD, chief of neurology, Nemours Children’s Hospital, and pharmaceutical companies changed the life-limiting trajectory for children diagnosed with spinal muscular atrophy (SMA), a genetic disorder affecting voluntary muscle movement. Nusinersen (a.k.a. Spinraza®), the FDA-approved drug proven to halt and reverse typical SMA disease progression, has shown such benefit that the FDA accelerated approval to include SMA in newborn screening.
So far, 17 U.S. states have added SMA to their newborn screening panels for early diagnosis and intervention with this life-saving treatment. Research shows that when the therapy is administered to very weak infants and children affected by SMA, it increases production of a critical motor neuron maintenance protein, effectively inhibiting the progression of SMA, increasing the chance of survival and even leading to improvement in muscle function. Astoundingly, pre-symptomatic newborns treated with Spinraza are often completely normal, suggesting that this therapy may allow children with SMA to grow up without experiencing the devastating effects of this disease.
A TRADITIONAL APPROACH TO MODERN MEDICINE
Imagine a place where patient care, community engagement and research are tightly integrated. A place where house calls are still commonplace, even as some of the most advanced work in genetic research is taking place. That place is Nemours Kinder Clinic — a community-based, patient-centered medical home serving medically complex children from the Amish Plain community of Delaware.
One such patient is Grace, who at two years old is reaching milestones that other family members sadly did not. Grace is part of a very small population born with a rare genetic disease called YARSopathy (seven known cases in the U.S.). Because of her cousins’ experiences, Nemours doctors were able to identify Grace’s YARS gene early on and have been able to keep her healthier as a result.
“Based on genetics of the Amish population, we know the exact genetic mutations; you can’t say that about diseases among the general population — yet,” says Michael D. Fox, MD, division of diagnostic referral, pediatrician, Nemours Kinder Clinic. “The big step is figuring out how to take what we’re learning and doing in this community and bring it to the broader population. As sequencing becomes more readily available, the development of screening panels that cover a wide range of diseases, not just those affecting Amish, will also become more readily available.”
Read or listen to “Saving Grace,” and in-depth, special report from Delaware Online.
Credits to Meredith Newman, health reporter, and Jennifer Corbett, staff photographer, Delaware Online.
Genetics Stewardship Program
Whether a child is born with medical issues or they develop over time, genetic testing can provide valuable insight. The Nemours Genetic Stewardship Program employs genetic counselors to ensure:
- appropriate tests are chosen based on the clinical features of the child;
- resulting reports are received by clinicians on a timely basis;
- care and treatment plans are developed based on test results;
- information is shared with families in a responsible manner; and
- guidance and coordination occur throughout the genetic testing process.
A Paradigm Shift for Cancer Care
Tropomyosin receptor kinases (TRK) gene mutations can be common in pediatric cancers, especially treatment-resistant cancers. Previously, the only treatments for these cancers were chemotherapy, radiation, and, in some cases, surgery — all of which can have serious adverse effects. A targeted drug therapy, aimed at treating genetic mutations in the tumors (rather than risking “off-target” damage to normal cells), is offering new hope to children with these types of cancers. The multicenter clinical trial was conducted at Nemours by Ramamoorthy Nagasubramanian, MD, division chief of pediatric hematology-oncology, Nemours Children’s Hospital. Designed to test the safety, dosing and effectiveness of the oral medication called larotrectinib (LOXO-101), the trial results are promising. More than 90 percent of the patients with solid TRK fusion-positive tumors in the trial showed sustained tumor regression. Of further significance, LOXO-101 is being tested in children nearly simultaneously with adults. Typically, this type of pediatric research lags years behind adult research.
A personalized approach to treatment through PRECISION medicine truly EMBODIES the Nemours MISSION: involving the patient and the family in their care for BETTER HEALTH outcomes.
Kids Deserve Better
The survival rate for children with acute myeloid leukemia (AML) hovers around 60 percent*. With support from the Leukemia & Lymphoma Society, Nemours is determined to do better. Using 2,000 samples from more than 900 children with AML, researchers are studying gene mutations at diagnosis, remission and relapse. Applying predictive analytics, the goal is to understand germ line events (that happen within the whole patient, not just the leukemia cells), define risk factors and better understand the components of relapse. The $1 million sequencing project will examine total body DNA and leukemia DNA. Using data, modeling and Artificial Intelligence to identify similarities and differences, the team will also work to develop precisely targeted therapies for pediatric AML.
*Survival rate for most common pediatric cancers is 80%.