What is substrate reduction therapy for Gaucher disease?

Substrate reduction therapy for Gaucher disease reduces glucosylceramide synthesis, which builds up in the cell due to a lack of the enzyme that degrades it, glucocerebrosidase (Figure 1).1 Miglustat was the first approved substrate reduction therapy in 2002, followed by eliglustat in 2014; both treatments are administered orally.2

The availability of these treatments differs between countries. For further information, please consult your local prescribing information.

Figure 1.
Substrate reduction therapy decreases the production of glucosylceramide in patients with Gaucher disease by inhibiting glucosylceramide synthase

What studies have been performed looking at patients' attitudes toward substrate reduction therapy?

The introduction of substrate reduction therapies for Gaucher disease allowed patients the first opportunity to have a choice regarding the type and method of treatment delivery (oral substrate reduction therapy versus intravenous enzyme replacement therapy).3 Studies of patients' attitudes toward enzyme replacement therapies can be accessed here.

In a US survey conducted in 47 adults with Gaucher disease, patients were asked questions surrounding their attitudes towards substrate reduction therapy. Thirty-two patients (68%) reported using enzyme replacement therapy, 14 patients (30%) were using substrate reduction therapy, and one patient (2%) was not currently receiving treatment. Of the 32 patients who were using enzyme replacement therapy, 23 (72%) had been offered a substrate reduction therapy by their physician in the past. Of the 14 patients who were currently receiving substrate reduction therapy, 12 (86%) had a previous history of enzyme replacement therapy.3


Of the patients currently receiving enzyme replacement therapy who had been offered substrate reduction therapy by their physician (n=23), reasons reported for declining substrate reduction therapy included3:

  • Potential or experienced side effects (n=16)
  • Not enough research (n=8)
  • Satisfaction with current treatment (n=5)
  • Convenience (n=2)
  • Barriers to substrate reduction therapy use (n=1)
  • Cost and insurance coverage (n=1).

When patients using substrate reduction therapy (n=14) were asked to provide reasons that contributed to the initiation of this type of treatment, reported reasons included3:

  • Convenience (n=7)
  • Less invasive than enzyme replacement therapy (n=4)
  • Reaction to enzyme replacement therapy (n=1)
  • Continued therapy after a Food and Drug Administration study (n=1)
  • Cost and insurance coverage (n=1)
  • Recommended by their physician (n=1).


Healthcare providers should discuss treatment options with patients with Gaucher disease, and should assess their perceptions of different therapy options prior to treatment initiation.3

Data were collected for this study between October 2015 and January 2016.3 These results should therefore be interpreted with caution, in light of the period the study was conducted and the study location. The availability of these treatments differs between countries. For further information, please consult your local prescribing information. Moreover, introduction to the market of each treatment differs for enzyme replacement therapies (imiglucerase, 1995; velaglucerase alfa, 2010; taliglucerase alfa, 2012) and substrate reduction therapies (miglustat, 2002; eliglustat, 2014),2 which may have influenced patient attitudes towards treatment depending upon when the study was performed.

C-ANPROM/INT//7568; Date of preparation: September 2020