Spinal muscular atrophy may also affect the heart

August 11, 2010, Nationwide Children's Hospital

Along with skeletal muscles, it may be important to monitor heart function in patients with spinal muscular atrophy (SMA). These are the findings from a study conducted by Nationwide Children's Hospital and published online ahead of print in Human Molecular Genetics. This is the first study to report cardiac dysfunction in mouse models of SMA.

SMA is a debilitating neurological disease that leads to wasting away of muscles throughout the body. Historically, scientists and physicians believed that SMA only affected skeletal muscles; however, 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 ," said the study's co-author Brian Kaspar, PhD, principal investigator in the Center for Gene Therapy at The Research Institute at Nationwide Children's Hospital. "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, developed by Arthur Burghes, PhD, professor of Molecular and Cellular Biochemistry at The Ohio State University College of Medicine, 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 in the heart of the SMA mice, along with severely impaired left-ventricular function. SMA mice also had significantly lower heart rates. After examining the underlying structure of the mouse they found it similar to the 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, PhD, director of the Center for Cardiovascular and Pulmonary Research at The Research Institute at Nationwide Children's Hospital and study co-author, says it is still not clear which mechanisms are fully responsible for the heart deficits seen in the SMA mice, but data suggests that neuronal, autonomic and developmental components all may play a role.

"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, also a faculty member at The Ohio State University College of Medicine.

More research is needed to determine whether the cardiac deficits are unique to the mouse or whether SMA patient of various severities have or will develop similar issues. Still, Kaspar, also on the faculty at The Ohio State University College of Medicine, says clinicians should be acutely aware of potential dysfunction in a subset of SMA patients.

"Increasing reports of autonomic dysfunction together with our current findings warrant increased attention to the cardiac status of SMA patients, and potentially highlights the need to investigate cardiac interventions alongside neuromuscular treatments," said Kaspar.

Related Stories

Recommended for you

Epigenetics study helps focus search for autism risk factors

January 16, 2018
Scientists have long tried to pin down the causes of autism spectrum disorder. Recent studies have expanded the search for genetic links from identifying genes toward epigenetics, the study of factors that control gene expression ...

Group recreates DNA of man who died in 1827 despite having no body to work with

January 16, 2018
An international team of researchers led by a group with deCODE Genetics, a biopharmaceutical company in Iceland, has partly recreated the DNA of a man who died in 1827, despite having no body to take tissue samples from. ...

Study advances gene therapy for glaucoma

January 16, 2018
While testing genes to treat glaucoma by reducing pressure inside the eye, University of Wisconsin-Madison scientists stumbled onto a problem: They had trouble getting efficient gene delivery to the cells that act like drains ...

The surprising role of gene architecture in cell fate decisions

January 16, 2018
Scientists read the code of life—the genome—as a sequence of letters, but now researchers have also started exploring its three-dimensional organisation. In a paper published in Nature Genetics, an interdisciplinary research ...

How incurable mitochondrial diseases strike previously unaffected families

January 15, 2018
Researchers have shown for the first time how children can inherit a severe - potentially fatal - mitochondrial disease from a healthy mother. The study, led by researchers from the MRC Mitochondrial Biology Unit at the University ...

Genes that aid spinal cord healing in lamprey also present in humans

January 15, 2018
Many of the genes involved in natural repair of the injured spinal cord of the lamprey are also active in the repair of the peripheral nervous system in mammals, according to a study by a collaborative group of scientists ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.