Developing a genetic therapy for spinal muscular atrophy

Professor Wood in his lab, University of Oxford

Professor Wood and his team are developing a molecular patch technology to treat spinal muscular atrophy (SMA). They are developing short protein fragments, called peptides, to help deliver molecular patches to the brain and spinal cord, eliminating the need for invasive spinal cord injections. This PhD studentship will test the potential therapeutic approach in mice with SMA and establish a safe, therapeutic dose. This is necessary before the potential therapy could be tested in clinical trials. 


This project is co-funded by Muscular Dystrophy UK and the SMA Trust – a collaborative partnership established to accelerate progress in the search for treatments and eventually cures for spinal muscular atrophy.

So far in this project the student has tested several peptides for their ability to deliver molecular patches that alter the SMN2 genetic code. The delivery of the molecular patches by the peptides has been studied in different cell types in the laboratory and in various tissues of a mouse model of SMA. The student also examined the effect and toxicity of the peptides in cells and in the SMA mouse model. The team has identified the most efficient peptide for delivering molecular patches to the central nervous system of SMA mice and showed there was no toxicity at the administered dose.

Not much is known about the dosage required to maintain effective levels of molecular patches in SMA mice and ultimately in patients. Therefore, the team is evaluating the response to different dose regimens for long-term treatment in the mice.

The student is also investigating how the molecular patches affect the level of other proteins and gene activity in SMA mice. By comparing treated with untreated SMA mice the researchers will see which molecular pathways are changed after treatment. This will help our understanding of how the peptide delivery system and molecular patches work, and will highlight how the peptides can be improved.

This year the work was presented by the student at the Oligonucleotide Therapeutics Society meeting in Leiden, Netherlands and in a poster presentation at the CureSMA meeting in Anaheim. The student has also contributed to a publication in a scientific journal on a related peptide project.

What are the researchers aiming to do in this project?

SMA is caused by mutations in the SMN1 gene which lead to a lack of SMN protein – which is crucial for motor neurones to survive. A second gene, called SMN2, also carries the information to produce SMN protein, but does not produce normal levels of SMN protein due to a change in its genetic code. However, the effects of this change can be overcome using an adapted form of exon skipping technology – using a short piece of DNA called a molecular patch to alter the way the SMN2 genetic code is read to allow larger amounts of protein to be produced.

A big challenge for this potential therapy is delivery; to maximise the therapeutic effect, the molecular patches need to access the brain and spinal cord. Injecting the molecular patches directly into the spinal cord overcomes this limitation, but this is invasive and not feasible as a long-term treatment strategy.

Professor Wood and his team have been developing and testing short protein fragments called peptides that can be linked to the molecular patches and allow them to reach the brain and spinal cord without the need for spinal cord injections.

In this project, the researchers will identify the one most efficient at delivering molecular patches to the central nervous system of a mouse model of SMA and establish the dose required. This work, if successful, will lead to further preclinical development work on the peptide-linked molecular patches which would be a necessary step before pursuing clinical trials.

How will the outcomes of the research benefit patients?

This PhD studentship will further the development of a potential gene therapy for SMA that eliminates the need for invasive spinal cord injections. The novel delivery system will ensure therapeutic molecular patches reach the entire body, including the brain and spinal cord, maximising its benefits. This work could pave the way to preclinical testing of the potential therapy in animal models, which would be a necessary step before clinical trials in humans.

Grant information

Project leader: Professor Matthew Wood
Location: Oxford University
Conditions: spinal muscular atrophy
Duration: three years, starting 2014
Total project cost: £82,173
Official title: Central nervous system delivery peptides conjugated to oligonucleotides for splice switching therapy of spinal muscular atrophy

Further information and links

Download a summary of this project

Learn more about spinal muscular atrophy

Read about other spinal muscular atrophy research projects we are funding

Read the latest research news for spinal muscular atrophy

It is only through your contributions that we can continue to fund the vital work that takes us closer to finding treatments and cures for muscle disease. Donate now and help change the lives of thousands of people living with muscle disease. Thank-you for your support.

Keep in touch