Literature Review #2

Some articles I found interesting and might be applicable to our research (Oct 10, 2012):

1. Gene therapy progress and prospects: gene therapy of lysosomal storage disorders

http://www.nature.com/gt/journal/v10/n16/abs/3302092a.html

The LSDs are monogenic and several small and large, representative animal models of the human diseases are available. Further, the successful reconstitution of only low and unregulated tissue levels of the affected lysosomal enzymes are expected to be sufficient to correct the disease at least in the case of some of the LSDs. For these reasons, they are perceived as good models for the evaluation of different gene delivery vectors and of different strategies for treating chronic genetic diseases by gene transfer. In this review, we will highlight the progress that has been made over the past 2 years in preclinical research for this group of disorders and speculate on future prospects.

2. CNS-directed gene therapy for lysosomal storage diseases

http://onlinelibrary.wiley.com/doi/10.1111/j.1651-2227.2008.00660.x/abstract;jsessionid=BDFC0264422B81ACD25FAB6DD547374C.d04t02?deniedAccessCustomisedMessage=&userIsAuthenticated=false
Gene therapy represents a promising approach for the treatment of CNS disease as it has the potential to provide a permanent source of the deficient enzyme to CNS. Direct intracranial injection of viral gene transfer vectors has resulted in reduced lysosomal storage and functional improvement in certain small (rodent) and large (canine and feline) animal models of LSDs. The addition of protein transduction domains (PTDs) to the recombinant enzymes increased the distribution of enzyme and the extent of correction. Therapeutic levels of lysosomal enzymes can also be delivered to distant sites in the brain by anterograde and retrograde axonal transport. Finally, combining disparate approaches such as BMT and CNS-directed gene therapy can increase treatment efficacy in LSDs with severe CNS disease that are refractory to more conventional approaches

3. Immune Responses to AAV in Clinical Trials (to download)

http://dx.doi.org/10.2174/156652311796150354
4. Potential of AAV vectors in the treatment of metabolic diseaseAAV vectors in the treatment of metabolic disease

http://www.nature.com/gt/journal/v15/n11/full/gt200864a.html

Achieving adequately widespread transduction within the central nervous system, however, remains a major challenge, and will be critical to realization of the therapeutic potential of gene therapy for many of the most clinically troubling metabolic disease phenotypes. Despite the relatively low immunogenicity of AAV vectors, immune responses are also emerging as a factor requiring special attention as efforts accelerate toward human clinical translation. Four metabolic disease phenotypes have reached phase I or I/II trials with one, targeting lipoprotein lipase deficiency, showing exciting early evidence of efficacy.

5. Review: Clinical Trial Outcomes

Gene therapy in neurology: review of ongoing clinical trials

http://www.future-science.com/doi/abs/10.4155/cli.12.47

Gene therapy has entered into its third decade since the first human clinical trial in 1990. The advances in clinical arenas, the successes in this field and the remaining obstacles are highlighted.

6. Gene Therapy Approaches for Lysosomal Storage Disease: Next-Generation Treatment

http://online.liebertpub.com/doi/abs/10.1089/hum.2012.140?mi=3fd470&af=R&prevSearch=allfield%253A%2528integrative+medicine%2529&filter=multiple&nh=20&searchText=integrative+medicine

Since the advent of enzyme replacement therapy (ERT) to manage some LSDs, general clinical outcomes have significantly improved; however, treatment with infused protein is lifelong and continued disease progression is still evident in patients. Viral gene therapy may provide a viable alternative or adjunctive therapy to current management strategies for LSDs. In this review, we discuss the various viral vector systems that have been developed and some of the strategy designs for the treatment of LSDs.