Substrate reduction therapy

Substrate reduction therapy (SRT), also known as substrate deprivation therapy, is a form of treatment for lysosomal storage diseases (LSDs). LSDs are a group of approximately 50 rare inherited metabolic disorders that result from defects in lysosomal function. SRT aims to reduce the accumulation of harmful substances in the cells of individuals with these diseases.

Overview

The principle of substrate reduction therapy is to decrease the production of the substance that accumulates in the cells due to a deficiency of a specific enzyme. This is achieved by inhibiting the synthesis of the substance, thereby reducing its levels and preventing or slowing the progression of the disease.

Mechanism of Action

Substrate reduction therapy works by inhibiting the synthesis of the specific substance that accumulates in the cells. This is achieved through the use of small molecules that can cross the blood-brain barrier and reach the cells where the substance is produced. These molecules inhibit the enzymes involved in the synthesis of the substance, thereby reducing its levels.

Applications

Substrate reduction therapy has been used in the treatment of several lysosomal storage diseases, including Gaucher's disease, Niemann-Pick disease, and Fabry disease. In Gaucher's disease, for example, the drug miglustat is used to inhibit the synthesis of glucocerebroside, the substance that accumulates in the cells of individuals with this disease.

Advantages and Limitations

One of the main advantages of substrate reduction therapy is that it can be administered orally, making it a more convenient option for many patients. Furthermore, because it targets the synthesis of the substance, it can potentially be used in combination with other treatments, such as enzyme replacement therapy (ERT), to enhance their effectiveness.

However, substrate reduction therapy also has some limitations. For instance, it may not be effective in all patients, and it may have side effects, such as diarrhea and weight loss. Moreover, it may not be able to completely stop the progression of the disease, especially in severe cases.

Future Directions

Research is ongoing to develop new substrate reduction therapies and to improve the effectiveness of existing ones. This includes the development of new drugs that can more effectively inhibit the synthesis of the substances that accumulate in the cells, as well as the use of gene therapy to correct the underlying genetic defects.