Friday 6 January 2012
Gene therapy clinical trial for spinal muscular atrophy started
Isis Pharmaceuticals has announced that it has started a Phase 1 clinical trial of an antisense oligonucleotide drug called ISIS-SMNRx in patients with spinal muscular atrophy (SMA). This safety trial based in the USA will test the drug in 24 children with SMA.
Antisense oligonucleotides (AOs) are small pieces of DNA which can bind to a specific gene and change how the code is read. This can be considered a type of gene therapy. AOs are currently in phase 3 clinical trial for Duchenne muscular dystrophy.
Spinal muscular atrophy (SMA) is caused by the lack of the SMN1 gene which is responsible for the production of a protein called "survival of motor neuron" or SMN. This protein is critical for the survival of motor neurons - the nerves that carry signals from the central nervous system to the muscle.
It is thought that AOs could be used to treat SMA because scientists can take advantage of the fact that everybody has at least one copy of a gene that is closely related to the SMN1 gene called SMN2. This gene mostly produces a shortened version of the SMN protein that does not work. However, AOs can be used to change the way the SMN2 gene is read, resulting in the production of full length, functional SMN protein. This approach has been successfully tested in mouse models of SMA - SMN protein was seen in the nerves and the lifespan of the mice was increased.
What will happen in this trial?
This first trial will focus on safety. They will also study how the body absorbs and processes the drug so they can work out the best dose for subsequent trials. Four different centres in the USA will carry out the trial; in Boston, New York, Dallas and Salt Lake City.
This trial will test the ISIS-SMNRx drug in 24 children with SMA between the ages of 2 and 14 who are medically stable. Participants will receive a single injection of the drug directly into the spinal fluid. They will receive one of four different doses. The lowest dose will be tested first and if this appears safe the next group of participants will receive the next highest dose, and so on up to the highest dose.
What does this mean for patients?
The commencement of this trial is very exciting because it is the first time that gene therapy approach has been tested in patients with SMA.
ISIS pharmaceuticals started a similar clinical trial one year ago for another condition called amyotrophic lateral sclerosis (ALS). This trial also involved injecting antisense oligonucleotides directly into the spinal column and this has been shown to be safe and well tolerated so far.
C. Frank Bennett, Ph.D., Senior Vice President of Research at Isis said:
We are committed to quickly developing this drug and are finalizing what we believe will be a rapid development path for this drug in all types of SMA. Once we evaluate ISIS-SMNRx as a single-dose in children with SMA, we will move to multiple-doses in our Phase 1 studies and eventually evaluate the drug in Phase 2 studies in children with SMA, including infants with Type I SMA.
Preliminary work into SMA therapies has indicated that treatments would need to be given early in life to have a beneficial effect. If this is the case, it would mean that newborn screening for SMA is a necessity, especially for the most severe form of the condition - SMA type 1.
Further information and links
Read the press release from Isis Pharmaceuticals.
More information about the trial.
Learn more about gene therapy in Target Research magazine.
Read about the SMA research we fund.
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