SMA Biomarker

Overview

Status: Recruiting
Keywords: SMA , Biomarker
IRB Number: 00058219
Specialty: Neurology
Sub Specialties: Spinal Muscular Atrophy

Brief Summary

Spinal muscular atrophy (SMA) is the leading genetic killer of infants. Strong preclinical evidence suggests that effective therapy must be delivered as early as possible to prevent progression of the disease. The primary study objective will be to identify prognostic and surrogate biomarkers of disease progression that will facilitate the execution of therapeutic SMA clinical trials in infants.

Aim 1. To establish the validity of putative physiological SMA biomarkers in the immediate postnatal period A longitudinal, natural history examination of physiological markers of muscle innervation will be performed in healthy and SMA infants. The first week of life is the ideal first time point, with visits occurring at scheduled visits up to the age two (2). Compound motor action potential (CMAP) amplitude and electrical impedance myography (EIM) will be examined and will be correlated with motor function. Each of these is associated with muscle innervation and provides information on the number and function of lower motor neurons in the spinal cord, the cellular target of SMA therapeutic interventions. This trial will establish the natural history of these putative SMA biomarkers as the disease evolves in affected infants. Moreover, our approach will allow for measurements in pre-symptomatic subjects and determine their predictive value.

Aim 2. To establish the validity of putative molecular SMA biomarkers in the immediate postnatal period. SMN2 copy number is a valid, predictive molecular SMA biomarker; however, it is fixed, and therefore not useful as a biomarker of clinical progression or response to therapy. SMN mRNA and protein expression is variable in different cell types and, in mice, naturally decreases with age postnatally. In this study, SMN expression levels will be measured longitudinally in SMA patients and controls. Additional putative molecular SMA markers that have been identified to correlate with motor function will be determined in an effort to distinguish between predictive markers that change prior to development of weakness and those that change as a consequence of weakness.

Principal Investigator: Kathryn Swoboda
Department: Neurology
Co Investigator:

Contact Information

Name:Tammy Floore
Phone: 801-585-5227
Email: tammy.floore@hsc.utah.edu

Inclusion Criteria

Infants will be between 0-24 months of age at the time of enrollment. Parents or guardians of the enrolled infants must sign an informed consent form prior to any study procedure being performed.

Healthy control infants who meet the following criteria will be enrolled:

Birth between 36 and 42 weeks inclusive of gestation

Siblings of children with SMA must have had prior SMA genetic testing completed confirming the infant is a healthy control

Principal investigator feels the family/infant is able and willing to comply with study procedures

Parent or guardian able to give informed consent

SMA infants who meet the following criteria will be enrolled:

Birth between 36 and 42 weeks inclusive of gestation

Positive SMN1 gene mutation/deletion

Principal investigator feels the family/infant is able and willing to comply with study procedures

Parent or guardian able to give informed consent

Exclusion Criteria

Infants will be excluded if they meet any of the following criteria:

Use of any putative therapy to increase SMN expression

Enrollment in an SMA therapeutic trial at the time of enrollment in the SMA biomarker study

Have a systemic illness requiring ongoing treatment

Any neurologic or other medical condition resulting in weakness, CNS changes, or that would interfere with the performance of the study (as determined by the investigator) on the physical examination or medical history