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

• INCLUSION CRITERIA:

Some restrictions are placed on participation in the study because we aim to identify disease biomarkers specific to those with early to intermediate stages of disease who would be potential candidates for future therapeutic studies.

In order to be eligible to participate in the SBMA cohort, an individual must meet all of the following criteria:

• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male, above the age of 18 years
• Genetically confirmed SBMA
• Ability of subject to understand and the willingness to sign a written informed consent document
• Ability of subject to travel to the NIH Clinical Center.

Note: an SBMA patient who meets both of the additional following criteria will be offered an optional whole body MRI at subsequent follow-up visits:

• Spinal bulbar muscular atrophy functional rating of \< 50 (and > 35).
• On initial whole body MRI, subject has evidence of muscle fat replacement such that the total volume of disease affected muscles (i.e., muscles with at least 10% muscle fat infiltration and no more than 50% muscle fat fraction) is at least:

• 500ml if only 1 muscle is eligible or
• 250ml if more than one muscle meets the criteria

In order to be eligible to participate in this study in the Healthy Control cohort, an individual must meet all of the following criteria:

• Stated willingness to comply with all study procedures and availability to travel to the NIH for the duration of the study
• Male, above the age of 18 years
• No history of SBMA or other neuromuscular disorder
• No history of facial palsy
• Ability of subject to understand and the willingness to sign a written informed consent document
• Ability of subject to travel to the NIH Clinical Center.

EXCLUSION CRITERIA

SBMA is a disease that affects males and manifests in adulthood. Thus, woman and children are not included in this study. This study will not include individuals who lack consent capacity.

An SBMA patient who meets any of the following criteria will be excluded from participation in this study:

• Contraindications to MRI such as a contraindicated non-removable metal device (i.e., pacemaker, defibrillator, insulin pump, metal clips, non-removable jewelry) or claustrophobia.
• Non ambulatory
• Use of androgen reducing agents within the past two years

Note: An SBMA patient who meets any of the following criteria will be excluded from the lumbar puncture procedure:

• PT/PTT values that are prolonged greater than or equal to 3 seconds from the upper limit of normal (including treatment with oral and parenteral anticoagulants)
• INR greater than or equal to 1.5, thrombocytopenia (\<70,000), or abnormal bleeding time or platelet dysfunction
• History of a bleeding disorder
• Use of anticoagulants

Note: An SBMA patient who meets any of the following criteria will be excluded from the muscle biopsy procedure:

• Advanced wasting of tibialis anterior that precludes needle muscle biopsy (in order to ensure that a sample taken would be of muscle and not just fat and fascia)
• Use of aspirin or non-steroidal anti-inflammatory agents 3 days prior to the procedure

Note: An SBMA patient who meets any of the following criteria will be excluded from the whole body MRI:

• Patient has a history of prior treatment with androgen reducing agents including LHRH agonists or antagonists, androgen receptor antagonists and selective androgen receptor modifiers.
• Patient is unable to complete the study assessments of QMT or timed walk tests.
• Patient anticipates making major lifestyle changes during the observation period relating to diet and exercise.

A Healthy Control participant who meets any of the following criteria will be excluded from the study:

• PT/PTT values that are prolonged greater than or equal to 3 seconds from the upper limit of normal (including treatment with oral and parenteral anticoagulants)
• INR greater than or equal to 1.5, thrombocytopenia (\<70,000), or abnormal bleeding time or platelet dysfunction
• History of a bleeding disorder
• Use of anticoagulants