Substrate reduction therapy

Substrate reduction therapy (SRT, engl. Substrate reduction therapy ) is a therapeutic method for the treatment of lysosomal storage diseases.

Principle

Through genetic enzyme defects, patients with lysosomal storage diseases specific macromolecules in some body cells no longer break down sufficiently. Thus, the non -degradable macromolecules accumulate in the cell, where they can cause damage to the cells and various organs constructed therefrom. When substrate reduction therapy, the patient orally available drugs that prevent the emergence of non-degradable substance obtained ( inhibit ) are. This leads to a reduction of the non-biodegradable substances in the cell. In the case of small molecules ( small molecules ), these compounds - as opposed to the enzymes in enzyme replacement therapy - capable of overcoming the blood -brain barrier. This also forms of lysosomal storage diseases Cerebral course can be treated. Not the disease itself treated or cured, but it can be used to treat symptoms of the disease - When the substrate reduction therapy - also as with enzyme replacement therapy. The patients must take the drugs for life at regular intervals.

Problem

The development of suitable agents for enzyme replacement therapy is extremely difficult. Firstly, there is - due to the very low prevalence of partial lysosomal storage diseases - very few patients for the conduct of clinical trials and other requirements relating to the safety of medicines over very long periods of intake are important. The drugs are to be taken for life. Due to the rarity of the diseases of the market for a developed drug is very small. The development costs thus spread over a small number of patients, which in turn has very high treatment cost per patient result.

Therapy example

Miglustat ( chemically: N-butyl- Deoxygluconojirimycin, also known as N - Butyldeoxynojirimycin, NB -DNJ, brand name Zavesca ® (CAS 72599-27-0 ) refers ), a glycosyltransferase inhibitor for oral treatment of mild to moderate type 1 Gaucher disease admitted ( in the U.S. since 31 July 2003). However, it should be used only in patients for whom enzyme replacement therapy is unsuitable in consideration. It is approved for this indication in the European Union, the USA, Canada, Switzerland, Brazil, Australia, Turkey and Israel. The reason for the limitation of the indication, the weaker activity (as compared to enzyme replacement therapy ), and the considerable side effects.

Miglustat inhibits the enzyme glycosyltransferase, which is the formation of glucocerebroside in the first step of glycosphingolipid synthesis - the storage substance in Gaucher disease - catalyzed. The approval of miglustat in the European Union for the treatment of Niemann -Pick type C disease was in 2009.