Abstract
ObjectiveTo determine whether blood biomarkers of neuronal damage (neurofilament light chain [NfL]), muscle damage (creatine kinase [CK]), and muscle mass (creatinine) are altered in spinal and bulbar muscular atrophy (SBMA) and can be used as biomarkers for disease severity.MethodsIn this multicenter longitudinal prospective study, plasma and serum were collected from 2 cohorts of patients with SBMA in London, United Kingdom (n = 50), and Padova, Italy (n = 43), along with disease (amyotrophic lateral sclerosis [ALS]) and healthy controls, and levels of plasma and serum NfL, CK, and creatinine were measured. Disease severity was assessed by the SBMA Functional Rating Scale and the Adult Myopathy Assessment Tool at baseline and 12 and 24 months.ResultsBlood NfL concentrations were increased in ALS samples, but were unchanged in both SBMA cohorts, were stable after 12 and 24 months, and were not correlated with clinical severity. Normal NfL levels were also found in a well-established mouse model of SBMA. Conversely, CK concentrations were significantly raised in SBMA compared with ALS samples, and were not correlated to the clinical measures. Creatinine concentrations were significantly reduced in SBMA, and strongly and significantly correlated with disease severity.ConclusionsWhile muscle damage and muscle mass biomarkers are abnormal in SBMA, axonal damage markers are unchanged, highlighting the relevant primary role of skeletal muscle in disease pathogenesis. Creatinine, but not CK, correlated with disease severity, confirming its role as a valuable biomarker in SBMA.
Highlights
In this multicenter longitudinal prospective study, plasma and serum were collected from 2 cohorts of patients with spinal and bulbar muscular atrophy (SBMA) in London, United Kingdom (n = 50), and Padova, Italy (n = 43), along with disease and healthy controls, and levels of plasma and serum Neurofilament light chain (NfL), creatine kinase (CK), and creatinine were measured
While muscle damage and muscle mass biomarkers are abnormal in SBMA, axonal damage markers are unchanged, highlighting the relevant primary role of skeletal muscle in disease pathogenesis
NfL levels are unchanged in 2 cohorts of patients with SBMA We measured the plasma levels of NfL, using the highly sensitive single molecule array (Simoa) assay, in samples from the UK SBMA cohort, and compared them with healthy controls and with slow and fast progressor amyotrophic lateral sclerosis (ALS) cases, as positive controls
Summary
In this multicenter longitudinal prospective study, plasma and serum were collected from 2 cohorts of patients with SBMA in London, United Kingdom (n = 50), and Padova, Italy (n = 43), along with disease (amyotrophic lateral sclerosis [ALS]) and healthy controls, and levels of plasma and serum NfL, CK, and creatinine were measured. Registrations, and patient consents Plasma and serum were prospectively collected with informed consent from 2 cohorts of patients with a genetically confirmed diagnosis of SBMA attending the KD clinic at the National Hospital for Neurology in London, United Kingdom (n = 50), and at the University Hospital in Padova, Italy (n = 43). Patient evaluation All patients were recruited in neuromuscular clinics at the National Hospital for Neurology in London, United Kingdom, and at the University Hospital in Padova, Italy. Healthy controls were excluded if they had coexistent neurologic disease as determined by a symptom and medical history–based questionnaire
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