The time-dependent plots of lung volume computed from the EIT data clearly show when the MIE device insufflates and exsufflates air and the rest periods between mechanical coughs. In four of the six subjects, lung volumes during tidal breathing increased after MIE (average change from pre to post MIE was 58.8±55.1 ml). Images of pulsatile pulmonary perfusion were computed in subjects able to perform breath-holding. Lung volumes were computed from the images and compared before, during, and after the MIE procedure to assess the ability of EIT to estimate changes in lung volume during insufflation and exsufflation. EIT data were collected before, during, and after the MIE procedure on two rows of 16 electrodes placed around the chest. A pilot study to investigate the feasibility of using three dimensional (3-D) electrical impedance tomography (EIT) images to estimate lung volumes pre- and post-MIE for assessing the effectiveness of mechanical insufflation-exsufflation (MIE) was conducted in 6 pediatric patients with SMA‐I in the neuromuscular clinic at Children's Hospital Colorado. The effect of mechanical insufflation-exsufflation (MIE) for airway clearance in patients with spinal muscular atrophy type I (SMA‐I) on the distribution of ventilation in the lung is unknown, as is the duration of its beneficial effects.
After describing the concept of splicing modulation, this review will cover the progress achieved in this field, by highlighting the breakthrough accomplished recently for the treatment of SMA using the mechanism of alternative splicing. Understanding the regulation of the SMN2 pre-mRNA splicing process has allowed for innovative treatment and the introduction of new medicines for SMA. A pathologically low level of survival motor neuron protein (SMN) causes degeneration of the anterior horn cells in the spinal cord with associated destruction of α-motor cells and manifested by muscle weakness and loss. The nearly identical SMN2 gene does not compensate for SMN loss caused by SMN1 gene mutation due to different splicing of exon 7. Homozygous deletion in 5q13 (the region coding for the motor neuron survival gene (SMN1)) is responsible for 95% of SMA cases. Spinal Muscular Atrophy (SMA) is an autosomal recessive neurodegenerative disease. Disturbed alternative splicing is observed in many disorders, including neuromuscular diseases and carcinomas. It is a crucial mechanism to increase genetic diversity. It has been estimated that 80% of the pre-mRNA undergoes alternative splicing, which exponentially increases the flow of biological information in cellular processes and can be an attractive therapeutic target.
0 kommentar(er)
