Patients with spinal and bulbar muscular atrophy (SBMA) may be at risk of developing respiratory complications due to a decline in the levels of genes responsible for muscle strength, according to a new study. The authors assert that monitoring the breathing decline in these patients may help provide better clinical management of the disease.
The study, “Decreased Peak Expiratory Flow Associated With Muscle Fiber-Type Switching In Spinal And Bulbar Muscular Atrophy,” was published in the journal PLoS One.
At more advanced stages of the disease, SBMA patients may develop dysphagia (difficulties in swallowing) and dyspnea (shortness of breath), as well as pneumonia and respiratory failure. Thus, the management of swallowing and respiratory function is indispensable for the long-term care of these patients.
However, respiratory difficulties associated with SBMA are not well characterized, which limits the knowledge of how these processes occur in patients and how they might be managed.
The objective of the study was to evaluate respiratory function of SBMA patients and identify the mechanisms underlying this condition, in comparison to patients with amyotrophic lateral sclerosis (ALS), another motor neuron disease in which dyspnea has been observed and well-studied.
The study included 40 SBMA and 25 ALS male patients, as well as 15 healthy individuals, in whom researchers evaluated respiratory function (by assessing the peak expiratory flow, %PEF, a measure of breathing capacity, and the forced vital capacity, FVC), motor function (using the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) or the Spinal and Bulbar Muscular Atrophy Functional Rating Scale (SBMAFRS)) and muscle strength (by assessing the modified quantitative myasthenia gravis (mQMG) score, that measures muscle weakness, tongue pressure, and grip power).
Researchers also collected bicep muscle biopsies from two patients with SBMA and two patients with ALS to evaluate the levels of myosin heavy chain (MHC) expression and other proteins involved in muscle activity.
Results indicated that %PEF and FVC were lower in SBMA patients compared to healthy individuals or ALS patients. Both parameters were found to be strongly correlated with disease duration, suggesting that both values can be biomarkers of respiratory function in SBMA patients and potentially be used to assess disease progression.
SBMA patients also had substantially decreased tongue pressure and grip power (measures of fast muscle power) compared to ALS patients. This probably is associated with a reduction in the expression of genes responsible for fast muscle power, observed in SBMA patients rather than in ALS patients.
“[W]e found that subjects with SBMA exhibited decreased %PEF, which appears to reflect the preferential involvement of fast-twitch [muscle] fibers in this disease,” the authors wrote. “Given that the leading causes of death in subjects with SBMA are pneumonia and respiratory failure, particular attention should be paid to %PEF decline during the clinical management of SBMA.”
SBMA is caused by the presence of repeat portions of DNA (called CAG repeats) within the gene encoding the androgen receptor, thereby affecting men. Muscular weakness generally appears between the ages of 30-60 years. Patients start using a wheelchair 15 to 20 years after the onset of symptoms.