Spinal Muscular Atrophy Neonatal Screening Program

Activation of the Spinal Muscular Atrophy Neonatal Screening Program and Integration With Cystic Fibrosis Screening. Feasibility Study

Spinal muscular atrophy (SMA) is a group of disorders caused by the degeneration of the motor neuron cells of the anterior horn of the spinal cord and, in some subtypes, of the bulbar motor neurons. Almost all cases are genetically determined. Most SMAs are autosomal recessive diseases, caused by homozygous deletions of the survival motor neuron (SMN) gene located on the long arm of chromosome 5. The estimated incidence of recessive childhood and juvenile SMA linked to deletion of the SMN gene is 1 in 6000 to 10000 live births, with a carrier frequency of 1 in 35 in the general population, making it a major genetic cause of infant mortality. Up to 95-97% of all childhood cases are due to homozygous deletions of the survival motor neuron 1 (SMN1) gene, or telomeric SMN, located on chromosome 5q11.2-13.3. The remaining 3-5% of cases are due to small mutations in SMN1 (rather than complete deletions).

Until a few years ago, the prognosis of type 1 SMA was poor. In the absence of therapies, the only measures were supportive (ventilation, nutrition) and the prospect, especially in the early forms, was to accompany them towards an early end of life. There are currently three treatment options available: nusinersen, risdiplam, and gene therapy with onasemnogene abeparvovec. The three options were found to be equally effective in reducing the symptoms of the disease, making it possible to reach or safeguard fundamental stages in a child's neuromotor development, starting from the ability to remain seated. At this moment, gene therapy is probably the preferred choice. To date, in Italy, there are approximately 100 patients undergoing gene therapy.

To ensure maximum benefit for affected patients, it is essential that the therapy is administered as soon as possible. Literature shows how the administration of gene therapy in pre-symptomatic subjects made it possible to achieve a better neurological outcome compared to symptomatic patients. From this perspective, the inclusion of spinal muscular atrophy in neonatal screening is of fundamental relevance.

Study Overview

• Status: Recruiting
• Conditions: Spinal Muscular Atrophy
• Intervention / Treatment: Diagnostic test: Screening SMA test

• Study Type: Observational
• Enrollment (Estimated): 11500

Contacts and Locations

• Study Contact: Name: Sheila Ulivi; Phone Number: 39 0403785226; Email: sheila.ulivi@burlo.trieste.it
• Study Contact Backup: Name: Stefania Zampieri; Email: stefania.zampieri@burlo.trieste.it

Study Locations

• Italy
  • Trieste, Italy, 34137
    • Recruiting
    • Institute for Maternal and Child Health - IRCCS "Burlo Garofolo"
    • Contact: Sheila Ulivi, MSc; Phone Number: +36.040 3785 226; Email: sheila.ulivi@burlo.trieste.it
    • Contact: Luca Ronfani, PhD MD; Phone Number: +39.040.3785.297; Email: luca.ronfani@burlo.trieste.it
  • Gorizia
    • Monfalcone, Gorizia, Italy
      • Recruiting
      • SC Pediatria Gorizia - Monfalcone
      • Contact: Danica Dragovic, MD; Phone Number: +39 0481 487252; Email: danica.dragovic@asugi.sanita.fvg.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Newborn babies born at the Neonatology Unit of the Institute for Maternal and Child Health Burlo Garofolo, Trieste, and at the Pediatrics Unit of the Gorizia-Monfalcone Hospital (Friuli Venezia Giulia-Italy)

Description

INCLUSION CRITERIA

• Live births in the neonatologies and paediatric centers involved in the study.

EXCLUSION CRITERIA

• No consent signed by parents.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Screening group; The patient enrollment takes place at the Neonatology Unit of the Institute for Maternal and Child Health Burlo Garofolo and at the Pediatrics Unit of the Gorizia-Monfalcone Hospital, which are the only two birth centers in the area of the Giuliano-Isontina University Health Authority

Diagnostic test: Screening SMA test; Drops of blood from a puncture from the newborn's heel are collected, dried for 24 hours at room temperature and then sent to the laboratory for analysis. The screening test is a first-level molecular genetic test that allows the identification of patients affected by SMA who present the homozygous deletion of exon 7 of the SMN1 gene using the Real Time polymerase chain reaction (PCR) technique. This qualitative method is based on the use of specific fluorescent probes that discriminate the SMN1 gene from its survival motor neuron 2 (SMN2) homologue and also allow the quality assessment of genomic DNA through amplification of an internal control gene. When a positive testing patient is identified, the birth center is promptly notified to call the family and carry out a further blood sample aimed at confirming the possible diagnosis with a second level test.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of newborn screened	Number of newborns screened per 100 live births	In the first 48-72 hours after birth

Collaborators and Investigators

• Sponsor: IRCCS Burlo Garofolo

Study record dates

Study Major Dates

• Study Start (Actual): October 16, 2023
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): May 31, 2026

Study Registration Dates

• First Submitted: March 7, 2024
• First Submitted That Met QC Criteria: March 7, 2024
• First Posted (Actual): March 15, 2024

Study Record Updates

• Last Update Posted (Actual): March 18, 2024
• Last Update Submitted That Met QC Criteria: March 15, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Spinal muscular atrophy; Newborn Screening
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neuromuscular Diseases; Neurodegenerative Diseases; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Spinal Cord Diseases; Motor Neuron Disease; Muscular Atrophy; Atrophy; Muscular Atrophy, Spinal
• Other Study ID Numbers: Screening_SMA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No