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Since the basal level of glycogen in the tgKO is significantly higher than in the KO, we extended the therapy by three additional injections and observed a further drop in glycogen, but a significant amount of glycogen remained (Figure 7A).
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We transferred 106 bone marrow cells derived from THOC5/FMIP flox/flox) mice into nonablated Mx-cre THOC5/FMIP flox/flox) mice via i.v. and a day after transplantation we injected recipient mice with poly (I C), followed by two additional injections.
Two additional injections were performed at days 35 and 70 after the first injection using same amount and antigen batches emulsified at 1∶1 in 1 ml of Alum.
57% of the eyes didn't require injections after laser, while 43% needed two additional injections.
In previous randomised trials the number of injections received by patients was considerably higher: in the CATT study, patients were treated with a mean of seven additional injections during the first year [ 16].
Interestingly, patients receiving more than five additional injections did not present a better improvement of VA at 15 months, compared with those who received four additional injections.
In open-label extensions to these studies (ClinicalTrials.gov NCT00956410; NCT01023685), patients received four additional injections of CAD106 at 12-week intervals (weeks 56, 68, 80, and 92) by s.c. or intramuscular (i.m).
This is supported by two additional considerations.
In order to fit the bolus injection phase, for 10 or the 24 subjects it was necessary to assume that a fraction of the bolus dose was sequestered and then slowly released from the lungs (characterized by two additional parameters).
Three additional booster injections were administered using incomplete adjuvant every 2 weeks.
13 Every retreatment due to new disease activity triggered three additional monthly injections.
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