Research ranging from tackling muscle regeneration for injured athletes to a potential cure for haemophilia has been presented at the American Society of Gene Therapy meeting at Baltimore, Maryland. A team from the University of Pittsburgh has successfully used gene therapy techniques to promote accelerated skeletal muscle healing in injured mice. The researchers injected mice with a gene that codes for a protein which blocks a muscle growth inhibitor, prior to inflicting muscle injury. Results after four weeks of healing showed enhanced muscle regeneration as compared to non-gene-therapy treated control mice. There was also significantly less fibrous scar tissue in the gene therapy mice. Formation of fibrous scar tissue can seriously impede recovery of athletes after muscle injury and may result in a lack of complete functional recovery.
In separate research, a team from the University of Iowa presented preliminary results describing their progress in designing a novel treatment for Huntington's disease (HD) using RNAi (ribonucleic acid interference) techniques. HD is an incurable genetic disease where a faulty gene leads to production of a mutated version of the protein huntingtin. It leads to a loss of cognitive abilities, involuntary movements and early death. RNAi is a technique that uses short sequences of RNA (a close chemical relative of DNA) to shut down or silence particular genes, and thereby prevents bad copies of proteins from being manufactured.
In previous research the team, led by Beverly Davidson, successfully used the approach to reduce levels of the huntingtin protein in mouse brains, in turn reducing the severity of the behavioural symptoms. However, people with the disorder have one mutated and one normal copy of the gene, and Davidson's technique so far targets both normal and mutated copies. Although huntingtin is known to be important in development its function in the adult brain is unclear. The new research presented in Baltimore describes how the team is now able to target only the mutated gene in 40 per cent of HD patients who carry a particular version of the faulty gene. It is thought that it will be several years before the therapy is ready to test in humans but the team is 'very optimistic' says Davidson.
In other research presented at the conference, a team from Milan is using microRNA to enable gene therapy to be used in diseases where patients have functioning immune systems that usually swiftly target and destroy vectors carrying therapeutic genes. MicroRNAs damp down the activity of particular genes in cells where they are not needed, and the team are exploiting this function to place vectors into mice which, so far have not been rejected.Researchers from Stanford University presented work looking at the long-term effects of high activity of short hairpin RNAs (shRNAs) used to target hepatitis B virus in the livers of adult mice. shRNA was delivered into mouse livers using a non-disease-causing monkey virus to induce RNA interference. The team found that there is a limit to the amount of shRNA molecules that can be tolerated by individual cells before toxicity and death occurs. Other research presented included a team developing small interfering RNAs (siRNAs) to inhibit Respiratory Syncytial Virus and a study, from the Salk Institute in California, which demonstrates a method of delivering proteins across the blood-brain barrier by piggy-backing onto existing receptors.