substrátcsökkent

Substrate reduction, referred to in Hungarian as substrátcsökkentés, is a therapeutic approach that aims to limit the buildup of a substrate that cannot be adequately degraded because of an enzyme deficiency. The strategy uses small molecules to inhibit enzymes in the substrate’s biosynthetic pathway, lowering the substrate load on cells and tissues.

In lysosomal storage diseases such as Gaucher disease, substrate reduction targets the production of glucosylceramide by inhibiting glucosylceramide synthase. This complements enzyme replacement therapy (ERT) by reducing substrate formation and, in some cases, enabling treatment of tissues less accessible to ERT. Approved agents include miglustat, which inhibits glucosylceramide synthase, and eliglustat, a more selective inhibitor with different pharmacokinetics.

Clinical use is primarily for Gaucher disease type 1, often in patients who are unable to receive ERT or prefer oral therapy. While SRT can improve hematologic and organ involvement, it may not fully control manifestations in all patients and can have adverse effects such as gastrointestinal symptoms. CNS involvement remains challenging for some substrates due to limited drug penetration across the blood–brain barrier.

Beyond Gaucher disease, research has explored SRT for other lysosomal storage disorders, including Niemann-Pick disease type C and emerging targets in other conditions. The field continues to evaluate long-term outcomes, safety, and combinations with other therapies.