Innovation and Impact at the Clinic for Special Children

Last Updated: Apr 15, 2020

By Adam Heaps, MS, MBA

For the last 31 years, the Clinic for Special Children (CSC) has provided integrated clinical, laboratory, research, and educational services to patients with genetic or other complex disorders in an unusual setting: rural Lancaster County.

The organization was founded to provide care primarily to children with metabolic disorders, such as Glutaric Acidemia Type 1 or Maple Syrup Urine Disease, from the area’s Old Order Amish and Mennonite (Plain) communities. It has since grown in scale and scope to care for patients with many types of disorders, some of whom come from well beyond Central Pennsylvania.

From the beginning, CSC has been an atypical outpatient practice. The complexity of disorders and the cultural context of providing primary and specialty care is certainly unique, but more importantly, innovative research and on-site advanced laboratory services have been an important focus. While the laboratory at CSC originally focused on the practical application of inexpensive and rapid biochemical assays, such as urine organic acids and blood amino acid quantitation, today the CLIA-certified clinical laboratory has the capability to rapidly genotype patients for specific genetic variants and even sequence DNA.

THE PRACTICAL APPLICATIONS OF THE RECENT ADVANCES IN SMA CARE ARE JUST A FEW EXAMPLES OF THE INNOVATIVE PROGRAMS AND SERVICES PROVIDED BY CSC.

clinic-special-children-cowsThe laboratory, clinical, and research teams at CSC focus on using the capabilities of the organization in practical ways that positively impact the natural history of a disease. The process of allowing patient needs to guide research that results in improved patient outcomes is called translational medicine. This strategy has been successfully applied to a number of projects and disorders at CSC, but most powerfully for recent innovations in the care of Spinal Muscular Atrophy (SMA) — a progressive neurological disease typically caused by a deletion within the SMN1 gene.

SMA is common worldwide, occurring in 1 in 10,000 births, but is even more common in Old Order Mennonite communities, with a frequency of around 1 in 3,600 births. The severity of the disease is dependent on the number of copies of the gene SMN2 that are present in SMA individuals. Those individuals with two copies of the SMN2 gene have SMA type 1, which is the most severe form of SMA. These children have onset early in infancy, are unable to sit or walk, and often die or require ventilator support by two years of age. On the other hand, individuals with three copies of SMN2 typically have SMA type 2, which is a less severe form of SMA. These children are able to sit unassisted but are unable to stand or walk. Historically, the only option for SMA care was symptom management.

The landscape of SMA treatment has changed significantly over the last three years. In late 2017, two articles were published in the New England Journal of Medicine showing the efficiency of two treatment options — one is an antisense oligonucleotide that increases the effectiveness of the SMN2 gene product and is delivered intrathecally into the cerebral spinal fluid (CSF) via lumbar puncture every four months after initial loading doses. The second is a gene replacement therapy.

At CSC, we were interested in giving Spinraza® (the antisense oligonucleotide treatment option mentioned above) to our existing patients with SMA type 1 and type 2 to hopefully halt or slow the progression of the disease. However, we immediately ran into a roadblock. Most older children and adults with SMA have severe scoliosis and spinal fusion, which makes it difficult, if not impossible, to perform a lumbar puncture to access the CSF in order to give the Spinraza®.

clinic-amish-manCSC partnered with Nemours/A.I. duPont Hospital for Children in Wilmington, Del., to develop a system for drug delivery where an indwelling catheter would be placed in the CSF and attached to a port anchored to a rib that sits under the skin. This allows Spinraza® to be administered without the need to perform a lumbar puncture every four months. CSC was able to expand this program, and the results from the first ten 10 subjects treated with this novel system were published in the Journal of Pediatric Orthopaedics in late 2018. Initial observations show the catheter system to be well tolerated and effective. This strategy is impactful locally for existing CSC patients as well as SMA patients across the world, demonstrating a clear model of translational medicine in action.

The disorder is recessive, which means that both parents are carriers of the SMN1 deletion, and an affected child has two damaged copies of the SMN1 gene. Outside of treating existing patients, CSC is also able to harness its laboratory capabilities to identify adults who are carriers of SMA so affected children can be treated as soon as possible. Thanks to funding it received, CSC was able to carrier test 2,177 healthy adults in 15 months, identifying 318 carriers, and nine couples where both spouses are carriers for SMA. This resulted in nine infants being genetically screened by our laboratory within the first day of life, and treatment started rapidly in three SMA infants.

adam_heaps 
Adam Heaps, MS, MBA, is the executive director of the Clinic for Special Children in Lancaster. Learn more about CSC at https://clinicforspecialchildren.org.

Pediatric Neurologist at CSC and PAMED member Vincent Carson, MD, explains, “Identifying couples who are carriers for SMA allows us to discuss treatment options and develop a game plan before a child is even born. The ability to diagnose infants with SMA on day one of life in our laboratory allows us to put that game plan into action quickly. This strategy provides affected newborns with the best possible chance to have a good outcome.”

The practical applications of the recent advances in SMA care are just a few examples of the innovative programs and services provided by CSC. The dedication of CSC’s 22 staff members to the more than 1,100 active patients served by the organization is a testament to how integrated, advanced laboratory capabilities, used in a timely and practical manner, coupled with a high-quality and creative clinical service, can produce innovative and impactful benefits for patient families.

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