SMN Circular RNAs as Potential New Targets and Biomarkers for SMA

NCT05760209 | Unknown

• 1 other identifier: 4348
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Spinal Muscular Atrophy (SMA) is a life-threatening disease in infancy that is caused by inactivating mutations in the Survival Motor Neuron 1 (SMN1) gene1,2. SMN1 mutations lead to deficiency in SMN protein, which results in degeneration of motor neurons in the spinal cord, progressive muscle weakness and atrophy. The almost identical SMN2 gene does not suffice SMN function, because skipping of exon 7 in its mRNA yields an unstable protein. Nevertheless, SMN2 represents a disease modifier gene and increasing its expression or rescuing its splicing defect have long been considered elective strategies for SMA1,2. After substantial translational research efforts, the first therapies eliciting clinical benefits for SMA patients have recently become available3. Nusinersen, an antisense oligonucleotide (ASO), and Risdiplasm, a small molecule, bind the SMN2 RNA and promote splicing of exon 7. On the other hand, Zolgesma, an adeno-associated virus delivering the SMN1 gene (scAAV9-SMN), bypasses the need to correct the splicing defect. Nevertheless, none of these therapies currently represents a complete cure for patients, because not all of them respond equally and in a significant portion of patients the symptoms are attenuated but not corrected3. It is believed that early treatment, possibly at a pre-symptomatic stage, would positively affect the clinical response and may significantly improve patient's management. However, another critical point is the current lack of information on the long-term efficacy and safety of the current treatments4. In this scenario, it is likely that further elucidation of the biological functions of the SMN genes and the identification of robust biomarkers for stratification of patients will set the ground for more "personalized" therapies, which may account for the clinical variability observed in patients and help improving the therapies in use.

Conditions

Spinal Muscular Atrophy

Keywords

biomarkers, spinal muscular atrophy; outcome

Outcome Measures

Primary Outcomes (1)

• survival motor neuron (SMN) circular RNA

  biomarker

  36 months

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

patients with SMA trewated according to standards of care

You may qualify if:

• Genetic diagnosis of SMA, without any restrictions for phenotype (i.e. presymptomatic patients, SMA 0, SMA I, SMA II, SMA III, SMA IV patients), number of SMN2, age or gender.
• Treatment with Nusinersen or Risdiplam or Zolgensma.

You may not qualify if:

• unable to provide consent

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead

Study Sites (1)

Policlinico gemelli

Rome, Italy

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

serum

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

Study Officials

• Eugenio Mercuri

  F Policlinico Gemelli IRCCS

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Eugenio Mercuri, MD

CONTACT

063015; eugeniomaria.mercuri@policlinicogemelli.it

claudio sette, phD

CONTACT

063015; claudio.sette@policlinicogemelli.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2023
• First Posted: March 8, 2023
• Study Start: July 22, 2021
• Primary Completion: July 21, 2024
• Study Completion: July 21, 2024
• Last Updated: March 8, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)