Spinal Muscular Atrophy Neonatal Screening Program

NCT06310421 | Recruiting

• 1 other identifier: Screening_SMA
• Study Type: observational
• Target: 11,500
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Spinal Muscular Atrophy

Keywords

Spinal muscular atrophy; Newborn Screening

Outcome Measures

Primary Outcomes (1)

• Rate of newborn screened

  Number of newborns screened per 100 live births

  In the first 48-72 hours after birth

Study Arms (1)

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

Interventions

Screening SMA test DIAGNOSTIC_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.

Screening group

Eligibility Criteria

• Age: 48 Hours - 72 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• 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)

You may qualify if:

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

You may not qualify if:

• No consent signed by parents.

Sponsors & Collaborators

• IRCCS Burlo Garofolo: lead

Study Sites (2)

SC Pediatria Gorizia - Monfalcone

Monfalcone, Gorizia, Italy

RECRUITING

Institute for Maternal and Child Health - IRCCS "Burlo Garofolo"

Trieste, 34137, Italy

RECRUITING

MeSH Terms

Conditions

Muscular Atrophy, Spinal

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; Neuromuscular Diseases

Central Study Contacts

Sheila Ulivi

CONTACT

39 0403785226; sheila.ulivi@burlo.trieste.it

Stefania Zampieri

CONTACT

stefania.zampieri@burlo.trieste.it

Study Design

• Study Type: observational
• Observational Model: ECOLOGIC OR COMMUNITY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 7, 2024
• First Posted: March 15, 2024
• Study Start: October 16, 2023
• Primary Completion: May 31, 2026
• Study Completion: May 31, 2026
• Last Updated: March 18, 2024

Record last verified: 2024-03

Locations

IT (2)