By the humane (AAV-T) or experimental (AAV-TC) endpoint the GM1-ganglioside content in all structures analyzed was higher than normal levels in control HZ mice (Fig. 3B, D, H – Endpoint light and dark gray bars).
Triglyceride (TG) and total cholesterol (TC) were assessed by endpoint method [ 13].
The critical endpoint temperatures (Tcs) of hydrogels, obtained from volume phase transition data upon changing the acetone concentration in aqueous solutions at various temperatures, were shown to decrease with the increasing acid or amide contents.
This was a 24-week placebo-controlled and randomized intervention trial to investigate the effects of GTP and TC on relevant primary and secondary endpoints in postmenopausal women with osteopenia.
Efficacy endpoints included lipid metabolism parameters such as TG, TC, low-density cholesterol (LDL-C), HDL-C, non-HDL-C, and TG/HDL ratio and glucose metabolism parameters such as FBG, HbA1c, and homeostasis model assessment insulin resistance (HOMA-R).
All but one AAV-TC GM1 mouse (n = 8) survived until the 52-week experimental endpoint (p<0.001, Log-rank test), despite their poor performance in motor tasks.
Secondary endpoints included mean percentage change from baseline of lipid profile (TC, LDL-C, HDL-C, TG, TC: HDL ratio), Framingham Cardiovascular Health Risk Score and absolute risk change from baseline in blood pressure parameters at week 24.
Measurements of TC binding to 43S·mRNA AUG) complexes or 43S complexes without mRNA revealed reaction endpoints and Kd values (<1 nM for 43S·mRNA AUG) complexes, Figure 8E) indistinguishable between WT and R148E mutant ribosomes, as were rates of TC dissociation (koff) from these complexes containing AUG start codons.
Other efficacy endpoints included mean percentage change from baseline of lipid profile (TC, LDL-C, HDL-C, TG, TC: HDL ratio), Framingham Cardiovascular Heart Risk Score, and absolute risk change from baseline in blood pressure parameters (systolic and diastolic) at week 24 and week 36.
Histological analysis of the eye at the humane endpoint (untreated GM1 and AAV-T GM1 mice), or 1 year of age (heterozygote mice, and AAV-TC GM1 mice) showed evidence of some βgal activity in the retinal ganglion cell layer (GCL) in both groups of AAV-injected GM1 mice compared to no detectable activity in the retinas of untreated GM1 mice (Fig. 8).
