2025 Research
Hearing Function in Spinal and Bulbar Muscular Atrophy (SBMA): A Case Control Study From a Tertiary Referral Center
Abstract
Background
Expanding on earlier findings of auditory involvement from two small‐scale studies, we conducted a comprehensive evaluation of hearing levels in a larger cohort of SBMA patients.
Methods
Thirty‐six SBMA patients and 36 age‐matched male controls without risk factors for hearing loss underwent a comprehensive audiological assessment, including pure‐tone audiometry at 250, 500, 1000, 2000, 4000, and 8000 Hz frequencies, using both air and bone conduction. The pure‐tone average (PTA) was calculated as the mean threshold at 500, 1000, 2000, and 4000 Hz. A correlation analysis was performed to evaluate the relationship between patients' audiological features and clinical characteristics, including motor disability, as measured by the SBMA functional rating scale (SBMAFRS) and the 6‐min walk test (6MWT).
Results
PTA values were significantly higher in SBMA patients compared to healthy controls (Mann–Whitney U test, p = 0.0005, and p = 0.0001 for the right and left side, respectively), even when analysis was restricted to the 19 SBMA patients without risk factors for hearing loss (Mann–Whitney U test, p = 0.0148 and p = 0.0243 for the right and left ear, respectively). In the latter group, the hearing thresholds of each individual frequency were significantly higher than in controls, except for the intermediate frequencies (2000 Hz on both sides and 1000 on the left one). Negative significant correlations were found between PTA values and both the CAG repeat number and 6MWT distances. Conversely, SBMAFRS scores were overall unrelated to PTA values.
Conclusions
Our findings suggest a disease‐specific hearing impairment in SBMA patients.
Read the research article, Hearing Function in Spinal and Bulbar Muscular Atrophy (SBMA): A Case Control Study From a Tertiary Referral Center
Neuromuscular junction transcriptome analysis of spinal and bulbar muscular atrophy mice implicates sarcomere gene expression and calcium flux dysregulation in disease pathogenesis
Abstract
X-linked Spinal and Bulbar Muscular Atrophy (SBMA) is a rare, late-onset neuromuscular disease caused by a CAG repeat expansion mutation in the androgen receptor (AR) gene. SBMA is characterized by progressive muscle atrophy of both neurogenic and myopathic etiologies. Previous work has established that mutant AR expression in skeletal muscle could be a significant contributor to neuromuscular decline, yet the mechanisms involved remain ill-defined. As AR is a nuclear hormone receptor transcription factor, we sought to define early changes in gene expression in skeletal muscle of pre-symptomatic SBMA mice, with a focus on transcriptional changes at the neuromuscular junction (NMJ). We describe loss of key NMJ-specific genes in synaptic muscle regions of pre-symptomatic SBMA mice, while extrasynaptic muscle features a coordinated loss of sarcomere genes that coincides with ectopic re-expression of certain NMJ genes. Furthermore, SBMA muscle prominently features dysregulated calcium flux, likely stemming from a compensatory response to early atrophy that greatly exacerbates over time. The SERCA activator CDN1163 conferred a mild rescue in function and muscle size in SBMA mice, while genetic deletion of the gene encoding Myf6/MRF4, a negative regulator of sarcomere gene expression and predicted AR interactor, did not ameliorate muscle atrophy. These studies suggest that modulation of calcium flux could be a promising pharmacological target in SBMA.
Read the research article, Neuromuscular junction transcriptome analysis of spinal and bulbar muscular atrophy mice implicates sarcomere gene expression and calcium flux dysregulation in disease pathogenesis.
Kennedy Disease in Latin America: Two New Mexican Cases and a Systematic Review of Regional Reports
Abstract
Spinal and bulbar muscular atrophy (SBMA), or Kennedy disease (KD), is a rare X-linked trinucleotide repeat disorder caused by cytosine, adenine, and guanine (CAG) expansions in the androgen receptor (AR) gene. KD affects lower motor neurons, leading to progressive muscle weakness, bulbar dysfunction, and endocrine symptoms such as gynecomastia. Diagnosis is challenging due to phenotypic overlap with other neurodegenerative diseases. This report aimed to describe two new Mexican cases of KD and to summarize all published cases of KD in Latin America through a systematic review (SR).
The SR search was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method in the Scielo, Lilacs, and Scopus databases, including cohort studies, case series, and case reports with molecular confirmation of SBMA. Clinical and molecular data were analyzed.
The review identified 23 Latin American SBMA cases. The median age of onset was 43 years (range: 21-66). The most common manifestations were weakness (95.7%; n = 22), tremor (65.2%; n = 15), and bulbar symptoms such as dysarthria (95.6%; n = 22) and dysphagia (91.3%; n = 21). Endocrine manifestations such as gynecomastia (73.9%; n = 17) and sexual dysfunction (56.5%; n = 13) were common. Electrophysiological findings confirmed lower motor neuron involvement, and molecular analysis revealed a median of 46.5 CAG repeats.
Despite its low frequency, SBMA remains underdiagnosed in Latin America, which may be due to limited awareness and clinical overlap with other pathologies. Molecular testing is crucial for diagnostic certainty. The review also highlights the need to evaluate multisystem involvement. Improved diagnostic protocols, genetic counseling, and increased awareness are needed for the timely detection and management of SBMA in Latin America.
Read the research article, Kennedy Disease in Latin America: Two New Mexican Cases and a Systematic Review of Regional Reports.
Conscience Announces Recipients of Inaugural Program to Foster Collaborative Drug Discovery and Development
TORONTO--(BUSINESS WIRE)--Conscience, a non-profit focused on accelerating drug discovery in areas of unmet medical need using open science and radical collaboration, is pleased to announce three recipients and projects have been approved for its Developing Medicines through Open Science (DMOS) program. The DMOS program is designed to foster collaborative drug discovery and development in areas often overlooked by the pharmaceutical industry, such as rare and orphan diseases and antimicrobial resistance. The inaugural round of this program is offering a total of $5M in funding and partnership opportunities to support significant advancements toward drug candidates. Project 1. Focus: Small Molecule PRMT6 Inhibitors for the Treatment of Spinal Bulbar Muscular Atrophy.
Read the article, Conscience Announces Recipients of Inaugural Program to Foster Collaborative Drug Discovery and Development.
The University of Rochester Announces the SBMA-Health Index, a rating scale for patient-related outcome measure for Kennedy's Disease. To view the rating scale, read the article, SBMA-HI: The Spinal-Bulbar Muscular Atrophy Health Index.
