Lysosomal storage diseases: treatment options

For some lysosomal storage disorders enzyme replacement therapy is available or is under development. In order to ensure that intravenously applied enzymes reach the central nervous system, methods to overcome the blood-brain barrier by modification of the enzymes or by the use of nanoparticles are being developed. Substrate deprivation represents another therapeutic option that is available for Gaucher disease and Niemann-Pick disease type C. One disadvantage of chaperones is the fact that they are effective only for patients with specific mutations. "Read-through" drugs will be useful only for patients who bear a nonsense-mutation. Presently gene therapy is being used as a therapeutic intervention for lysosomal storage disorders only in clinical trials. Before this treatment can be declared a routine therapeutic procedure, many questions have to be answered regarding, for example, long-term safety, immune reactions and organ specifity of the vector used for insertion of the gene. In many countries, newborn screening for lysosomal storage disorders has been introduced to allow timely initiation of treatment before any clinical manifestation occurs. However, since by screening many more cases have been found than was expected from epidemiological studies, it must be assumed that also such patients are being detected who are very mildly affected and probably do not need any therapy. As the severity of a disease cannot be predicted precisely by mutation analysis, a decision as to when to start treatment may be difficult in individual cases. No solution has been found for this dilemma to date.