Substratreduktionsterapien

Substratreduktionsterapien, or substrate reduction therapies (SRTs), are a class of pharmacological treatments designed to reduce the production of specific toxic substrates within cells. These therapies are primarily developed for lysosomal storage diseases, a group of genetic disorders caused by deficiencies in lysosomal enzymes. When an enzyme is lacking, its corresponding substrate accumulates in the lysosome, leading to cellular dysfunction and a range of clinical symptoms. SRTs work by inhibiting the enzymes involved in the synthesis of these accumulating substrates. By reducing the rate at which these substrates are produced, SRTs aim to decrease their cellular accumulation, thereby alleviating the downstream pathological effects of the lysosomal storage disease.

The most common substrates targeted by SRTs are glycosphingolipids, which accumulate in diseases such as Gaucher disease, Fabry disease, and Niemann-Pick disease types C. These therapies do not replace the deficient enzyme but rather lower the burden of the substrate that needs to be processed. This approach can be particularly beneficial when enzyme replacement therapy is not feasible or sufficient. SRTs are typically administered orally, offering a more convenient route of administration compared to intravenous infusions. While effective in managing symptoms and slowing disease progression for certain lysosomal storage disorders, SRTs may not completely normalize substrate levels and their long-term efficacy and safety profiles continue to be evaluated through ongoing research and clinical trials.