Clinical, Molecular and Imaging Biomarkers in Spinal and Bulbar Muscular Atrophy (SBMA)

Background: SBMA is an inherited chronic disease. It affects males in mid to late adulthood. It causes slowly progressive weakness of muscles and hand tremors. Researchers want to learn more about the effects of SBMA. Objective: To identify measurements that change over time in SBMA, including tests of muscle strength and function, as well as measurements of muscle and fat size. Eligibility: Men over the age of 18 both with and without a history of SBMA. Design: Participants will have a medical history, physical exam, and blood and urine tests. They will have neuromuscular ultrasound. They will have a lumbar puncture to obtain spinal fluid. For this, a needle will be inserted into the spinal canal in the lower back. Participants will have muscle strength and function tests. These tests may include pushing, pulling, rising from a chair and sitting back down, and/or walking. During these tests, they may wear an accelerometer (activity tracker) on their wrist. Participants will get an activity tracker to wear on their wrist for 10 days at home every 3 months. Participants with SBMA will also have lower limb magnetic resonance imaging (MRI) and optional whole-body MRI. They will have lung function tests. They will have speech and swallow tests. They will complete questionnaires. They may have optional body scans to measure bone density and lean body mass. They may have optional muscle biopsies. For biopsies, a needle will be used to take a small piece of muscle from the leg. Participants with SBMA will have 5 study visits over 2 years (every 6 months). Participants without SBMA will have 1 study visit.

Study Description: Spinal and bulbar muscular atrophy (SBMA) is an inherited form of motor neuron disease caused by a CAG-repeat expansion in the androgen receptor gene on the X chromosome for which there is no treatment currently. Biomarkers will be collected from participants with SBMA during this study to understand the natural history and progression of the disease. Objectives: The main objective of this study is to develop clinical, molecular and imaging outcome parameters that correlate with disease progression and severity and that predict clinical decline. These biomarkers and outcome measures can serve as potential tools for the evaluation of efficacy in future therapeutic studies in SBMA. Endpoints: The studies performed under this protocol are exploratory. However, the following measures may be used to characterize baseline status and disease progression over the course of the study: Muscle strength by manual and quantitative myometry Distance traveled in meters on the 6-minute walk test Activity levels and parameters of gait as measured by accelerometers Global disability measured by the SBMAFRS questionnaire and other tools/instruments Fatigue as measured by the Fatigue Severity Scale Breathing function measured by pulmonary function test Swallow and speech function measured by questionnaires, tongue muscle strength, digital audio recordings for analysis of voice and speech, and barium swallow Skeletal muscle MRI measurement of muscle volume and fat fraction Whole body MRI measurement of body muscle fat fraction, muscle fat infiltration, and liver. Skeletal muscle ultrasound measurement of muscle thickness, echogenicity and elasticity Nerve ultrasound measurement of nerve cross sectional area and anterior posterior diameter Laboratory studies from blood, serum, urine, stool, and CSF Muscle biopsy assessment of androgen receptor levels and function