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Page last updated: 17th September 2011


In 2009, two independent research groups showed that a single intravenous (administered into a vein) injection of harmless viruses into 1-2 day old mice and cats was able to reach the nervous system and infect up to about 60% of motor neurons. To do this, they engineered the viruses to contain a gene that expresses a protein called Green Fluorescent Protein (GFP). GFP appears green under blue light, so the scientists were able to calculate the number of successfully infected nerve cells. This approach of packaging a particular gene into viruses that can target most, if not all, cells and tissues in the body has great potential for the treatment of SMA. Given that the lower motor neurons are the principle cells affected by SMA, it was a critical result that the viruses were able to successfully find and infect the nerve cells.

In 2010, this same approach was used to replace the survival motor neuron (SMN) protein in severe SMA mice by Brian Kaspar and colleagues at the Centre for Gene Therapy, OH, USA. Not only was there an impressive improvement in motor function (i.e. the ability to use and control muscle movement), but an unprecedented extension of lifespan. The mice used in this study normally live for about two weeks when untreated; however, when the study was submitted for publication, the mice injected with viruses containing the SMN gene were still alive and healthy after well over 200 days.

This improvement in lifespan of SMA mice through gene therapy has been corroborated by the group of Mimoun Azzouz at the University of Sheffield, UK, through work funded by the Jennifer Trust (now SMA UK), and Martine Barkats’ laboratory at the Institut de Myologie in Paris, France.

In principle, the results in SMA mice show that the defects caused by low levels of SMN protein can be rescued by virus-mediated SMN gene replacement.

In the 2010 Kaspar laboratory study, in order to assess the possibility of being able to translate this type of treatment to human patients, the researchers intravenously injected GFP-expressing viruses into one day old macaque monkeys (a type of primate like humans) and looked for GFP expression 25 days later. Importantly, the results were similar to what was seen in mice; GFP was found in the nervous system including the motor neurons, and all animals tolerated the treatment well.

In a recently published follow-up study from the Kaspar group, the virus expressing GFP was shown to be efficient at infecting the nervous system, muscles and organs of the macaque. This time, GFP expression was analysed three months after the initial injection. Motor neurons, muscles, and glial cells, which are cells that help to support, maintain and protect the nervous system, were all successfully infected by the virus. Promisingly, two weeks after administration, motor neurons expressing GFP were also found in three year old monkeys, indicating that gene replacement may be possible at later stages of life in humans. In addition, the injection of GFP-expressing viruses into the nervous system of five day old pigs resulted in the efficient targeting of motor neurons and parts of the brain.

Unfortunately, the GFP signal seen in macaque heart muscle was lower relative to skeletal muscle (i.e. muscles, such as the biceps, that allow us to move parts of our body). This is an important point because the heart appears to be an organ that is affected in more severe cases of SMA; therefore any potential therapy will likely need to target this organ.

Nevertheless, this most recent work in macaques and pigs has added to the evidence that a gene replacement therapy such as the one discussed here could be a viable future option for the treatment of SMA. After the arduous process of altering various experimental factors so as to optimise both the efficacy and safety of the approach, such a therapy may perhaps soon be advanced to the clinic.

Further Information

The abstract from The Azzouz Group Article >

The abstract from The Barkats Group Article >

The abstract from The Kaspar Group Article that uses macaques and pigs >