Potential Nephrocalcinosis Risk Linked to Nusinersin: Insights from FAERS-Based Signal Detection and Molecular Docking
Author(s)
YASHWANTH G R, Jr., MPH PHARMACY PRACTICE1, Eswaran Maheswari, Dr., PhD2.
1STUDENT, M S RAMAIAH UNIVERSITY OF APPLIED SCIENCES, BENGALURU, India, 2PHARMACY PRACTICE, M S RAMAIAH UNIVERSITY OF APPLIED SCIENCES, BENGALURU, India.
1STUDENT, M S RAMAIAH UNIVERSITY OF APPLIED SCIENCES, BENGALURU, India, 2PHARMACY PRACTICE, M S RAMAIAH UNIVERSITY OF APPLIED SCIENCES, BENGALURU, India.
OBJECTIVES: Nusinersen is a trailblazing therapy for spinal muscular atrophy, which is an autosomal-recessive disorder characterized by degeneration of motor neurons in the spinal cord. The well-known neurologic adverse effects of nusinersen include arachnoiditis, aseptic meningitis, headache, hydrocephalus, meningitis and reaction to post-lumbar puncture. This study aimed to identify the novel signals reported for nusinersen utilizing the USFDA Adverse Event Reporting System (FAERS) database.
METHODS: A disproportionality analysis was performed using the FAERS database for Nusinersen. Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR) were calculated using the Open Vigil database, with positive signals defined as PRR≥2, ROR - 1.96SE>2, chisquare>4 and adverse events>2. Bioinformatics databases like Gene Cards, Omim Gene Map were utilized to retrieve the genes. The pubchem was utilized to identify the targets of nusinersen. The InteractiVenn was utilized for identifying the common gene targets of nusinersin and nephrocalcinosis. The STITCH, STRING, Cytoscape and Cytohubba were employed to identify nephrocalcinosis-associated proteins and genes. Molecular docking was performed using Schrodinger software to explore the binding affinity of associated genes and proteins.
RESULTS: Nusinersen was approved by the U.S. Food and Drug Administration on 23rd December, 2016. Analysis of FAERS database revealed 6685 cases associated with Nusinersen, of which 218 cases pertained to nephrocalcinosis. The Open Vigil data showed the ROR of 14.941(5.588; 39.954), PRR of 14.932(5.588; 39.9), chi square value of 37.58 and 4 events of interest confirmed nephrocalcinosis as a positive signal. Bioinformatics analysis and molecular docking revealed GAPDH, EGFR and TNF as potential common targets of neusinersin and nephrocalcinosis with the binding affinity of -6.055, -3.882 and -7.602 respectively.
CONCLUSIONS: This study identified nephrocalcinosis as a potential adverse signal associated with Nusinersen. The findings highlight the need for further pharmacogenetic and epidemiological investigations to validate this signal and explore underlying mechanisms and risk factors.
METHODS: A disproportionality analysis was performed using the FAERS database for Nusinersen. Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR) were calculated using the Open Vigil database, with positive signals defined as PRR≥2, ROR - 1.96SE>2, chisquare>4 and adverse events>2. Bioinformatics databases like Gene Cards, Omim Gene Map were utilized to retrieve the genes. The pubchem was utilized to identify the targets of nusinersen. The InteractiVenn was utilized for identifying the common gene targets of nusinersin and nephrocalcinosis. The STITCH, STRING, Cytoscape and Cytohubba were employed to identify nephrocalcinosis-associated proteins and genes. Molecular docking was performed using Schrodinger software to explore the binding affinity of associated genes and proteins.
RESULTS: Nusinersen was approved by the U.S. Food and Drug Administration on 23rd December, 2016. Analysis of FAERS database revealed 6685 cases associated with Nusinersen, of which 218 cases pertained to nephrocalcinosis. The Open Vigil data showed the ROR of 14.941(5.588; 39.954), PRR of 14.932(5.588; 39.9), chi square value of 37.58 and 4 events of interest confirmed nephrocalcinosis as a positive signal. Bioinformatics analysis and molecular docking revealed GAPDH, EGFR and TNF as potential common targets of neusinersin and nephrocalcinosis with the binding affinity of -6.055, -3.882 and -7.602 respectively.
CONCLUSIONS: This study identified nephrocalcinosis as a potential adverse signal associated with Nusinersen. The findings highlight the need for further pharmacogenetic and epidemiological investigations to validate this signal and explore underlying mechanisms and risk factors.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
RWD136
Topic
Clinical Outcomes, Epidemiology & Public Health, Real World Data & Information Systems
Topic Subcategory
Distributed Data & Research Networks
Disease
Urinary/Kidney Disorders