SMA is a debilitating neurological disease that leads to wasting away of muscles throughout the body. Historically, scientists believed that SMA only affected skeletal muscles. New data suggests that this genetic disease may also impact the heart.
"A few studies regarding SMA patients have implicated the involvement of the cardiovascular and the autonomic nervous system," said the study's co-author Brian Kaspar. "However, there have been few to no highly powered and controlled studies to determine how common these cardiovascular anomalies are in these patients."
The reports of altered blood flow and slowed heart rate in some SMA patients prompted Kaspar's team to examine whether a cardiac deficit is present in a mouse model of severe SMA, which is routinely used for drug and therapeutic-based screening.
They analyzed heart structure of the SMA mice compared with normal mice, and found that there were significant structural changes occurring, along with severely impaired left-ventricular function. SMA mice also had significantly lower heart rates. After examining the underlying structure of the mouse heart cells they found it similar to the cellular structure of a heart biopsy from patient with type 3 SMA.
Kaspar's team recently developed a gene therapy approach shown to successfully deliver the missing SMN protein to SMA mice and improve neuromuscular function. Next, the team studied whether the discovered heart defects could be corrected by this gene delivery treatment. Results showed that restoring SMN levels completely restored heart rates and prevented the early development of dilated cardiomyopathy.
Pam Lucchesi, director of the Center for Cardiovascular and Pulmonary Research at The Research Institute at Nationwide Children's Hospital (USA), says it is still not clear which mechanisms are fully responsible for the heart deficits seen in the SMA mice.
"Our gene delivery strategy has unique advantages in that it targets neurons within the central and peripheral nervous system as well as the cardiac tissues," said Lucchesi.
MEDICA.de; Source: Nationwide Children's Hospital