Tuesday 7 August 2012
Results of a gene therapy trial for LGMD 2C
Results have recently been released for the Phase 1 clinical trial of a gene therapy for limb-girdle muscular dystrophy type 2C (LGMD2C). The trial organisers used a virus to introduce a healthy copy of the gamma-sarcoglycan gene - the gene that is affected in LGMD2C - into one wrist muscle of nine people with LGMD2C. They found that none of the participants suffered from a serious side effect as a result of the therapy and four of the participants started to produce gamma-sarcoglycan protein in the treated muscle.
A group of researchers in collaboration with the company Genethon, have released results of their phase 1 clinical trial of a gene therapy for LGMD2C. Their aim was to test if it was safe to use a virus - called an adeno-associated viral (AAV) vector - to deliver a healthy copy of the gamma-sarcoglycan gene to a single muscle of individuals with LGMD2C.
They recruited nine participants who were divided into three groups with each group receiving a different dose of the virus containing the healthy gene. The gene therapy was injected into a muscle in one wrist of each of the participants and they were monitored for up to 6 months.
The researchers found that all three participants who received the highest gene therapy dose and one patient from the middle-dose group had gamma-sarcoglycan present in the injected muscle. None of the participants suffered from any serious side effects.
A potential problem with gene therapy approaches is that participants may make an immune response to either the newly produced protein (since it has not been produced by the body before, the immune system sees it as foreign) or to the viral vector. Encouragingly, the researchers did not find evidence that the immune system was mounting a response against the new gamma-sarcoglycan protein. However, several of the participants had pre-existing antibodies against the viral vector and those who did not, developed antibodies during the trial. AAVs are viruses which naturally infect humans without causing disease, but this means people may have been previously infected by them and developed antibodies. The researchers suggested that the existence of the antibodies may have limited the effect of the gene therapy and may have been the reason why no gamma-sarcoglycan was seen at lower virus doses.
The researchers are now doing more pre-clinical work which will help them plan for a second trial that will aim to deliver the viral gene therapy to a whole limb.
This trial has provided proof of principle that a viral vector could be used to deliver a healthy copy of the gamma-sarcoglycan gene into muscle to treat LGMD2C. This trial was primarily aimed at testing the safety of the therapy and so future trials will determine if the gamma-sarcoglycan that is produced has a positive benefit for muscle strength or function.
Listen to a podcast from March 2012 about the trial featuring one of the organisers, Prof Thomas Voit
Read more about limb girdle muscular dystrophies
Read about research we fund into limb girdle muscular dystrophy
Find out about a gene therapy approach we are funding for Duchenne muscular dystrophy
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.