A new orally administered replacement therapy to restore enzyme activity


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Dr Edward Ginns, Director of Research in Pediatric Neurology at the University of Massachusetts Medical School in the USA is working on a technique to be taken by mouth that can deliver DNA directly to the macrophage cells of patients with Gaucher disease and other lysosomal storage disorders.


'Dr Gary Ostroff and I have developed an orally administered replacement therapy based on bakers yeast particles that can carry DNA directly to macrophage cells to restore normal enzymatic or other missing protein activities in tissues in lysosomal storage disorders such as Gaucher disease,' Dr Ed Ginns told delegates attending the National Gaucher Foundation Conference in Virginia on 14 November 2004.

'Following oral administration, the yeast particles containing the required human DNA are taken up in the intestine by Peyers Patches macrophage cells which then move the human DNA to the site of storage in the tissues. Within the tissue macrophage cells, the DNA encoding the required enzyme is released, resulting in newly produced normal human enzyme in lysosomes.

'We have already applied this technique to Gaucher disease. In both normal and long-lived Gaucher mutant mice this orally administered treatment results in human glucocerebrosidase production in mouse macrophages and in substantial correction of enzyme activity in many tissues, including the spleen, liver and lung.

'Our research has demonstrated that the yeast cell delivery vehicle is orally bioavailable and is targeted to tissue macrophages, including those in bone. Studies on brain are in progress.

'Preliminary findings also suggest that this orally administered replacement therapy ameliorates the symptoms in treated, compared to untreated, severely affected Gaucher mice.

'These encouraging preclinical data, along with results from ongoing therapeutic trials with Gaucher mice, provide the rationale to apply this new therapeutic approach to treat Gaucher Disease in human clinical trials.

'Dr Ginns has been carrying out research into Gaucher disease since his work with Dr Rosco Brady at the National Institutes of Health near Washington where he helped develop enzyme replacement therapy for Gaucher disease in the 1980s.'


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Source: Gauchers News May 2005.
Copyright © Gauchers Association 2005.