Kenyon Engineering News Vol 1-1

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These studies tested the hypothesis that increased M6P content on rhGAA will increase its affinity of interaction with CI-MPRs, and result in higher amounts of intravenously administered rhGAA being internalized by CI-MPRs and delivered to lysosomes. Stepwise Enzymatic Modification of rhGAA The N-glycans of acid hydrolases undergo a two-step modification in the Golgi to acquire the M6P tag: (1) GlcNAc-1-phosphotransferase recognizes a lysinecontaining, conformation-dependent motif unique to soluble acid hydrolases and adds GlcNAc-1-phosphate to selected mannose residues to form a phosphodiester, M6P-GlcNAc (Hasilik et al.

Thus, it is apparent that much critical work remains to be done in order to optimize therapy for these rare, but devastating diseases. S. Kishnani References Anderson LJ, Henley W, Wyatt KM, Nikolaou V, Waldek S, Hughes DA, Pastores GM, Logan S (2014) Long-term effectiveness of enzyme replacement therapy in children with Gaucher disease: results from the NCS-LSD cohort study. J Inherit Metab Dis 37(6):961–968 Banugaria SG, Prater SN, Ng YK, Kobori JA, Finkel RS, Ladda RL, Chen YT, Rosenberg AS, Kishnani PS (2011) The impact of antibodies on clinical outcomes in diseases treated with therapeutic protein: lessons learned from infantile Pompe disease.

Subsequent studies indicate that clenbuterol has both CI-MPR-dependent and CI-MPR-independent effects on the efficacy of rhGAA treatment in Pompe mice (Farah et al. 2014). Although preliminary, as this pilot study did not include placebo controls, β2-agonist treatment of adult Pompe patients with albuterol showed that CI-MPR protein expression was increased in three of the patients as assessed by Western blot analysis of quadriceps muscle biopsy, and improvements were noted in the 6-min walk test for all seven subjects (Koeberl et al.

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