ABSTRACT
Becker muscular dystrophy (BMD) is the milder allelic variant of Duchenne muscular dystrophy, with higher dystrophin levels. To anticipate on results of interventions targeting dystrophin expression it is important to know the natural variation of dystrophin expression between different muscles and over time. Dystrophin was quantified using capillary Western immunoassay (Wes) in the anterior tibial (TA) muscle of 37 BMD patients. Variability was studied using two samples from the same TA biopsy site in nine patients, assessing nine longitudinal TA biopsies, and eight simultaneously obtained vastus lateralis (VL) muscle biopsies. Measurements were performed in duplicate with two primary antibodies. Baseline dystrophin levels were correlated to longitudinal muscle strength and functional outcomes. Results showed low technical variability and high precision for both antibodies. Dystrophin TA levels ranged from 4.8 to 97.7%, remained stable over a 3-5 year period, and did not correlate with changes in longitudinal muscle function. Dystrophin levels were comparable between TA and VL muscles. Intra-muscle biopsy variability was low (5.2% and 11.4% of the total variability of the two antibodies). These observations are relevant for the design of clinical trials targeting dystrophin production, and may urge the need for other biomarkers or surrogate endpoints.
Subject(s)
Biomarkers , Dystrophin/metabolism , Gene Expression , Immunoassay , Muscle, Skeletal/metabolism , Muscular Dystrophy, Duchenne/genetics , Muscular Dystrophy, Duchenne/metabolism , Adolescent , Adult , Aged , Biopsy , Child , Child, Preschool , Dystrophin/genetics , Humans , Immunoassay/methods , Infant , Middle Aged , Muscle, Skeletal/pathology , Muscular Dystrophy, Duchenne/diagnosis , Mutation , Young AdultABSTRACT
The ability of changes in the distribution of technetium-99m-hexamethylpropylene amine oxime (99mTc-HMPAO) to reflect physiologic changes in regional cerebral blood flow (rCBF) was evaluated using photic stimulation, a procedure known to increase rCBF in the striate cortex. Seven healthy subjects were injected with 740 MBq 99mTc-HMPAO on two separate days. On one day, the injection was performed following closure of the eyes and patching for 5 min. On the other day, subjects were exposed to a stroboscopic light to produce photic simulation. Images of distribution of 99mTc-HMPAO were obtained using a Strichman 810X single-photon emission computed tomogram (SPECT) brain scanner. Comparison of images obtained during light occluded versus stimulation conditions revealed a significant increase in distribution of radiopharmaceutical in visual cortex relative to whole brain (peak increase corrected for radiopharmaceutical backdiffusion 36.7% +/- 6.6%). HMPAO appears to provide a useful method for detecting relative rCBF increases with SPECT.
