How did we get here and where are we going?

Objective: To identify the breakdown of pharmacist interventionswithin a newly established IMD adult service based at UniversityHospital Birmingham.

Method: Data was collected over a one year period using 3 differentsources. All prescribing was captured using an accurate and reliableprescribing system used within the hospital, called PICS. The number ofitems prescribed was recorded. Secondly the IMD database where mostcommunications with patients and interventions should be documentedwas used to capture any form of drug related intervention. Lastly emailswere used as a final source to highlight any interventions that had beencarried out over the one year period that were not included within theother two sources.

Results: 301 interventions were recorded, of which 57 (19%)interventions were drug histories for outpatient clinics. 136 (45%)interventions were prescribing and supplying of medication eitherthrough the hospital or as a letter of recommendation to the GP. 41(14%) interventions were purely clinical interventions and 66 (22%)were interventions relating to homecare services.

Discussion: The first three months of this job was to learn andunderstand the various types of inherited metabolic diseases, tounderstand how a specialist centre for IMD operates on a day to daybasis, to understand the financial and homecare aspects as well as toestablish a good rapport with the IMD team and with patients.Outpatient attendance to clinics started several months in to the role,hence the potential reason for fewer clinical interventions. Recom-mendations for future intervention audits could include othercentres, both adult and paediatric pharmacist interventions and acomparison of the different types of interventions made. The mainlimiting factor with this audit was data capture. The information thatwas captured was recorded data. However, this can be a usefullearning point for the future to ensure all interventions are recordedaccurately and efficiently for future auditing purposes. This datacollection was a good exercise to highlight and provide more detailinto the various areas Pharmacists can use their knowledge and skillsto assist their IMD team in improving patient-centred outcomes.

doi:10.1016/j.ymgme.2013.12.101

90How did we get here and where are we going?

Gregory A. Grabowski, Cincinnati Children's Hospital Medical Center,Cincinnati, OH, USA

From the discovery of the lysosomes by Christian deDuve, the need forlocalization signals was evident for targeting of proteins to this organelle.These signals could have intracellular or extracellular functions, but thefinal common path was to the lysosome. Equally evident was the use ofsuch signals for reconstituting deficient proteins in the lysosome. The socall lysosomal diseases (LSD) became the targets of investigation formorethan 3 decades as the signals were raveled, i.e, themannose 6-phosphate,carbohydrate, and peptide signals. In the past two decades the success intreating Gaucher disease spurred investment and progress in treatingseveral other LSD. However, the basic understanding of the LSD in generaland specifically is rudimentary and in many lacking. To make significantadditional progress in treating LSD effectively will require continuinginvestment in delineating their basic pathogenesis. The paths towardintegrative approaches will be highlight by clinical and basic research inGaucher disease, the saposin deficiencies, and lysosomal acid lipasedefects over the past 2.5 decades and how the approaches and strategieshave evolved and how these apply to the larger group of LSD. The majorquestions presented by these disorders are relevant to other LSD.Importantly, the lessons from these investigations have expanded toinclude the understanding of the potential roles of LSD gene defects in

more common diseases, including neurodegenerative diseases (e.g.,Parkinsonism) and atherogenesis. Developing innovative interventionsfor such diseases will require knowledgable applications of in silico, exvivo, and in vivo model systems as well as highly trained and motivatedphysican/scientists and basic researchers with expertise in these fieldsworking as collaborative groups. This presentation will focus on theessential need for such groups and the huge and rewording opportunitiesfor new investigators in these exciting fields. There is much to do!

doi:10.1016/j.ymgme.2013.12.102

91Taliglucerase alfa: an enzyme replacement therapy using plantcell expression technology

Gregory Grabowskia, Myriam Golembob, Yoseph Shaaltielb, aCincinnatiChildren’s Hospital Medical Center, Cincinnati, OH, USA, bProtalixBiotherapeutics, Carmiel, Israel

Gaucher disease (GD) is a rare, genetic lysosomal disorder caused byfunctional defects of acid β-glucosidase (glucocerebrosidase [EC3.2.1.45]) that results in multiple organ dysfunction. Glycosylation ofrecombinant human acid β-glucosidase and exposure of terminalmannose residues is critical to the success of enzyme replacementtherapy (ERT) for the treatment of visceral and hematologic manifesta-tions in GD. Currently, three ERT are commercially available for thetreatment of GD type I (GD1); two are produced in mammalian cell-based systems. Imiglucerase is produced in a Chinese hamster ovary[CHO] system and velaglucerase alfa is produced in a human fibrosar-coma cell line. Imiglucerase and velaglucerase alfa require post-production or post-translational glycosylationmodifications, respective-ly, to expose terminal α-mannose residues, which are needed formannose receptor-mediated uptake by target macrophages. Suchmodifications add to production costs. Taliglucerase alfa is a new acidβ-glucosidase that is approved in the United States and other countriesfor the treatment of GD1 in adults; it is the first approved plant cell-expressed biotherapeutic. A plant-based expression system, using carrotroot cell cultures, was developed for production of taliglucerase alfa anddoes not require additional processing for post-production or post-translational glycosidic modifications. Clinical trials have demonstratedthe efficacy and safety of taliglucerase alfa in adult ERT-naïve patientswith symptomatic GD1 and for such patients previously treated withimiglucerase. These included significant improvements in organomegalyand hematologic parameters as early as 9 months, and maintenance ofachieved therapeutic values in previously treated patients. Ongoingclinical trialswill further characterize the long-termefficacy and safety oftaliglucerase alfa in more diverse patient populations, and may help toguide clinical decisions for achieving optimal outcomes for patients withGD1. This presentation will focus on the developmental history oftaliglucerase alfa.

doi:10.1016/j.ymgme.2013.12.103

92Age-dependent analysis of inflammatory markers in cartilagetissue of GALNS knockout mice

Shane Grace, Catalina Sosa, Adriana Montano, Saint Louis UniversitySchool of Medicine, St. Louis, MO, USA

The mucopolysaccharidoses (MPS) are inherited metabolic disor-ders resulting from defective catabolism of glycosaminoglycans

Abstracts S49