New Enzyme Trial


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During a recent meeting of the European Study Group of Lysosomal Disorders in Oslo during September 2005, Prof Ari Zimran from the Gaucher Clinic at Shaare Zedek Medical Center presented the six months results from the Phase I/II clinical trial of a new enzyme preparation for patients with Type I Gaucher disease produced by Transkaryotic Therapeutics (TKT) which is now owned by Shire Pharmaceuticals.


'The new enzyme was developed by TKT using the company's proprietary gene activation technology, and is called "gene-activated human glucocerebrosidase" (GA-GCB) reports Prof Zimran'. 'GA-GCB has an amino acid sequence identical to the naturally occurring human enzyme, and this is in contrast to Cerezyme, which has a single amino acid change at position 495 (histidine instead of arginine). GA-GCB also has terminal mannose residues that target the enzyme to macrophages, the primary target cells in Gaucher disease.

'The aims of the study (like any Phase I/II trial) were to evaluate the safety and efficacy of GA-GCB in adult patients (age 18 years and above) with Type I Gaucher disease. Twelve patients (7 females and 5 males) enrolled in the study to receive GA-GCB every other week for a total of 40 weeks (20 infusions). Patients either had not received any Cerezyme or had not received medication for their Gaucher disease for at least one year prior to treatment with GA-GCB. One patient withdrew consent after three infusions for reasons not related to treatment. All patients tolerated treatment well at 60 U/kg after 6 months and infusion reactions and adverse events were mild and transient. No antibodies (to the infused enzyme) were detected in any patient.

'Hemoglobin and platelet levels, spleen and liver volume, and disease biomarkers were evaluated after six months of GA-GCB treatment. Mean hemoglobin increase was 1.9 g/dL (all patients increased by more than 1 g/dL) and the mean platelet count increased by 23.4%. Liver and spleen volumes were studied by MRI and analyzed as multiple of normal organ volumes.'

Six months of treatment with GA-GCB showed a statistical significant reduction of the liver and spleen volumes. In addition, mean levels of the disease biomarkers chitotriosidase and CCL18 decreased coincident with the improvements in hematologic parameters and organomegaly'.

Prof Ari Zimran (Principle Investigator) and Dr Deborah Elstein (Study Co-ordinator) said that 'These results are similar to those published in the trials of Ceredase and Cerezyme, although, in the current study (unlike the former ones) no children (patients younger than 18 years of age) were enrolled. The results suggest that GA-GCB, if approved, could provide an alternative therapy for patients with Gaucher disease'.


See 9 month results
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Source: Gauchers News December 2005.
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