Impact of Nusinersen on Neurofilament, Creatinine Levels, and Motor Function in Pediatric Spinal Muscular Atrophy Rehabilitation: A Biomarker Analysis

Abstract

Background: Spinal amyotrophy is a rare, neurodegenerative disease, with progressive evolution, disabling until death in severe forms, but for which 3 disease-modifying drugs have recently been approved (in the last 8 years). In this context, it became necessary to find predictive factors for the evolution of patients and for the effectiveness of the treatment applied to personalize the therapy to obtain the best results according to the particularities of each patient. Objective: The objective of this retrospective study is to analyze the evolution of different clinical (motor functional scales) and paraclinical biomarkers (level of pNF-H neurofilaments in serum and cerebrospinal fluid and of serum creatinine) under treatment with nusinersen in various types of spinal muscular atrophy (SMA). Methods: We analyzed the biomarkers values for a group of 69 pediatric patients diagnosed with SMA in different stages of treatment over three years, depending on the type of SMA, the number of copies of the SMN2 gene, and the age at initiation of therapy. Results: We observed significant increases in the levels of pNF-H neurofilaments in both cerebrospinal fluid (CSF) and serum, with correlations to the age of symptom onset in patients and an inverse relationship to the number of copies of the SMN2 gene. These levels decreased during treatment with nusinersen, coinciding with increased serum creatinine values and improved motor functional assessment scores. The most pronounced effects were noted in patients with severe forms of the disease, such as SMA type 1, mainly when treatment was initiated at a younger age. Conclusion: The evolution of patients under disease-modifying treatments should be analyzed both for the evolution on specific motor functional scales, as well as against the biomarkers of neuronal degradation: pNF-H, present in CSF and serum, and serum creatinine, a marker of muscle activity. Administering the disease-modifying treatment promptly after diagnostic confirmation halts neural degradation and enhances the patient's motor function. Keywords: spinal muscular atrophy; neurofilaments; cerebrospinal fluid; biomarkers; nusinersen; creatinine; motor evolution