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Gene therapy: "...Keeping an eye on clinical trials 2008"

Here is a good article that describes important aspects of a clinical trial strategy in addition to discussing briefly the nature of the study--from Nature on line:

2008 promises to be an exciting one for ocular gene therapy. 2007 saw the start of 3 clinical trials of gene therapy for inherited retinal degeneration. These trials mark the culmination of decades of international research in ocular genetics and experimental ophthalmology and by the end of 2008 some of the results... are likely to be available.

The potential for gene therapy in this area has benefited from significant progress in the mapping and cloning of retinal disease genes, of which more than 120 have been identified to date.…Inherited retinal degenerations resulting from single gene defects affect approximately one in every 3000 individuals....there is no treatment option currently available....

The 3 clinical trials are all aimed at the same form of inherited retinal degeneration: early-onset severe retinal degeneration (Leber's congenital amaurosis). This is caused by defects in the gene encoding the enzyme RPE65, which is an isomerase critical for normal retinoid cycling in the retinal pigment epithelium. Individuals with defects in RPE65 have absent/very poor night vision and poor central vision with a predictably progressive degeneration. As they can have relatively well-preserved retinal structure, gene replacement offers the possibility of an improvement in visual function, measurable within the short term.…

Each of these trials have started with adult subjects and have a strong emphasis on evaluating safety and toxicity but they will also address the beneficial potential in terms of visual function…If the feasibility and safety of subretinal vector delivery can be demonstrated in young adults, then children will be included in subsequent phases of each trial.

The 3 clinical studies are a landmark for the development of ocular gene therapy….Although it is expected that they will demonstrate a clear benefit of applied gene therapy, the first clinical trials for inherited disease will also have important implications for the field and it is critically important that expectations are not raised disproportionately and the results are interpreted in an appropriately balanced fashion.

(1) http://www.nature.com/gt/journal/v15/n9/full/gt200828a.html
Gene Therapy (2008) 15, 633–634; doi:10.1038/gt.2008.28; published online 13 March 2008; JW Bainbridge and RR Ali, Division of Molecular Therapy, UCL Institute of Ophthalmology and Faculty, UCL and Moorfields Eye Hospital Biomedical Research Centre for Opthalmology, London, UK. E-mail: r.ali@ucl.ac.uk

See below for more on:
-- What are the unique advantages the eye has as a target organ for the development of novel therapies and is often regarded as a valuable model system for gene therapy.
--Is there any value in running three similar trials concurrently?
--Which institutions are involved in the UK and USA?

The eye has unique advantages as a target organ for the development of novel therapies and is often regarded as a valuable model system for gene therapy. 1. It is a relatively small target organ with highly compartmentalized anatomy in which it is possible to deliver small volumes of adeno-associated virus or lentiviral-based vectors very precisely and obtain efficient and stable transduction of a variety of ocular tissues with attenuated immune responses. 2. The risks of systemic side effects for eye procedures are minimal. 3. If only one eye is treated, the untreated eye may serve as a useful control. 4. Although gene therapy might be used first as a treatment for relatively rare single gene disorders, it also offers a potentially powerful modality for the management of much more common complex acquired disorders, such as those involving angiogenesis.
Is there any value in running three similar trials concurrently?....The differences in study protocol between these trials in terms of vector titre, promoter sequences and inclusion criteria are expected to yield complementary data that will help to inform on optimal vector design and define a window of opportunity for the timing of intervention.
Which institutions are involved?
In February 2007, the first clinical trial began in the United Kingdom at UCL Institute of Ophthalmology and Moorfields Eye Hospital. By the end of the year, two additional trials had started in the United States— one at Scheie's Center for Hereditary Retinal Degenerations, University of Pennsylvania and the University of Florida College of Medicine in Gainesville and the other at the University of Pennsylvania and Children's Hospital of Philadelphia.

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