National Gaucher Foundation - Gaucher Disease
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Two approaches to treat Lysosomal Storage Diseases

Enzyme therapy proves effective in treating LSDs, whilst gene therapy is an upcoming contender.


Lysosomes are membrane-bound organelles found in most animal cells. They are responsible for treating cellular waste. Genetic mutations in lysosomal enzymes lead to lysosome malfunction and waste accumulation. And this leads to a whole range of complex metabolic disorders, collectively called Lysosomal Storage Diseases (LSD). There are two kinds of LDSs: those that affect the brain (neuropathic) and those that do not (non-neuropathic). The EU-funded EUCLYD project, completed in 2011, studied four non-neuropathic LSDs out of the 50 currently known. These were Gaucher disease, Pompe disease, the mucopolysaccharidosis (MPS) VI and the multiple sulfatase deficiency.

Enzyme replacement therapy was one of the approaches successfully implemented by the project. "As the name suggests, it consists of artificially synthesising the malfunctioning enzyme and administering it to patients through an injection every seven to fifteen days," says project coordinator Generoso Andria, director of the Paediatrics Department of the University of Naples, Italy. The newly synthesised enzyme is then able to reach the lysosome directly and perform its functions. The project also studied a gene therapeutic approach. "We can operate 'upstream' with respect to the enzyme therapy," Andria tells "We prepared a viral vector that could insert the normal gene directly in the affected chromosome," he explains, adding: "In December 2012 we started testing this gene therapy to make sure it is not toxic. And we plan to recruit patients soon."

Importantly, the project also changed how the lysosome is viewed. "We used to think that the lysosome functioned as the 'incinerator' of the cell," explains Andria. "It is quite an appropriate metaphor, at least here in Naples, with all the waste problem we have had," he adds jokingly. Yet the reality is a bit more complicated than that, as Andria tells "Just as with the waste in a city, we realised that rather than 'incinerating', for the lysosome, it is more efficient to 'recycle' different molecules, like sugars, after degrading them."