Gene Therapy in Mouse Model Gives Insight into Possible SMA Treatments

by Lauren Taylor from In The Cloud Copy

Spinal muscular atrophy, or SMA, is a genetic disease that affects an individual’s central and peripheral nervous systems, as well as their skeletal muscles, which control voluntary muscle movements. SMA occurs due to the loss of motor neurons, which are nerve cells. There are various forms of SMA, and all affect the individual differently. The most common symptom is weakness or loss of control of voluntary muscles. SMA eventually takes away the individual’s ability to eat, walk, and breathe. It is the number one killer of genetic nature in infants.

SMA is caused by a mutation in the survival motor neuron gene 1 or SMN1. This gene is responsible for producing the protein that helps the nerves that control muscles to function. Without SMN1, the nerve cells do not function as they should and eventually die away. There are various types of SMA, which are based on symptoms onset and the highest physical milestones that can be achieved.

Gene Therapy Shows Promise in Mouse Model

A recent study on the production of a protein called docking protein 7 or DOK7, is showing promising results in an SMA mouse model. The study found that in mice affected by SMA, increasing the production of DOK7 improved the neuromuscular junction structure, improved grip strength, reduced muscle fiber loss, and ultimately extended survival times in the mice.

The protein, DOK7, is essential in SMA research as it plays a vital role in the neuromuscular junction development. It is at this neuromuscular junction that the nerve cells ultimately connect to the muscles they are intended to control. In SMA, inadequate levels of the SMN protein impair the proper formation of the neuromuscular junction.

The team investigating this, located at the University of Missouri, delivered the gene for DOK7 to mice that had lesser forms of SMA in terms of severity of disease. The mice did have the ability to walk but lacked other skeletal control of muscles.

The DOK7 gene was given to the mice via IV, one day after birth. It was delivered via adeno-associated virus or AAV, which is a commonly used vector when administering gene therapy.

17 days after administration, the DOK7 levels had increased in the back legs’ skeletal muscles of the mice. The overproduction of DOK7 did not ultimately impact the SMN protein levels. Mice treated with DOK7 lived 22.2 days, while untreated mice averaged a lifespan of 21.2 days. Grip strength was tested on all four limbs and showed significant improvements at the mid-stage disease progression point in the treated mice compared to the mice that were not treated.

The DOK7 seemed to prevent the reduction in the endplate area where the nerve impulses are received by the muscles. DOK7 also improved muscle fiber area significantly in the treated mice compared to those untreated.

These results demonstrate that DOK7 can play an important protective role, as well as improve motor activity. This study gives researchers further evidence that DOK7 could be a possible therapy for patients suffering from SMA and other diseases that are neuromuscular in nature.

Learn more about this story here.

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