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  • tech_210 tech_210 Jan 17, 2011 2:08 PM Flag

    ACT’s SMD Trial Must Evaluate ABCA4 & ELOVL4 Gene Replacement generation

    >>What genes are related to Stargardt macular degeneration?
    In most cases, Stargardt macular degeneration is caused by mutations in the ABCA4 gene. Less often, mutations in the ELOVL4 gene cause this condition. The ABCA4 and ELOVL4 genes provide instructions for making proteins that are found in light-sensing (photoreceptor) cells in the retina.<<

    IMO, for meaningful results, ACT’s donor hRPE from their hESC source will certainly contain both the ABCA4 & ELOVL4 genes so that the donor’s hRPE can carry out the necessary phagocytosis action in which the SMD patient’s diseased RPEs were not able to. The donor’s hRPE, if allowed to by the donor’s immune system, should then be removing dead cells from the patient’s (1)photoreceptors, (2) RPEs and (3) Bruch membrane plus whatever other surrounding tissue would normally be kept “clean” by the RPEs. The Phase I safety aspect of the trial will be evaluating safe co-existence of the donor’s RPEs vs. patient’s RPEs and other patient’s surrounding eye tissues. The hope is that the RPEs, donor’s and patient’s, are the good guys and will not attack each other but co-exist peacefully. As long as the patient’s eye tissues remain in an immune-privilege state with no seeping bleeding, then there is a good chance for success. While peaceful co-existence was the case for the rat/mice/animal trials, the human genetic/immune system with the much longer life span exponential magnitude, will no doubt pose a much greater challenge. Hence the Phase I safety evaluation before being allowed to move forward with the Phase II Efficacy evaluation with greater than 50K cells.

    These same concerns will also apply to the DAMD patients but perhaps without the ABCA4 & ELOVL4 genes replacement.

    In time the donor’s RPE will need to be regenerated as dictated by its telomere actions. This regeneration will then be a major crossroad as to what ACT will evaluate as to the best course of action.

    It is expected that the additional hESC injections will likely be needed after several months unless the patient begins to regenerate new hRPEs. The ACT team can then make an assessment at this time as to whether any of their autologous therapies would be more beneficial in complete restorative eye cells.

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