Enzyme Replacement Therapy, Substrate Reduction Therapy & Symptomatic Treatment

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In view of the genetic nature of Gaucher disease, there is currently no cure available Therefore, the ultimate goal of Gaucher disease management is to reduce the accumulation of the toxic substrate glucocerebroside and other glycolipids to prevent progressive disease with serious complications.1 This can be achieved either by Enzyme Replacement Therapy (ERT) or Substrate reduction therapy (SRT).

As Gaucher disease is variable in its presentation and manifestations, physicians can individualize treatment goals for each patient by taking into account all possible signs and symptoms, and identify treatment goals for each of these conditions.1-3

A panel of global experts agreed on a consensusÂfor eight therapeutic goals of treatment inÂGaucher disease, including:3

  1. Hepatomegaly (reduce liver volume)
  2. Splenomegaly (reduce spleen volume)
  3. Skeletal pathology (address bone pain, bone crises)
  4. Anemia (improve hemoglobin level)
  5. Thrombocytopenia (increase platelet count)
  6. Growth (normalize pediatric population)
  7. Pulmonary involvement (improve lung function)
  8. Functional health and wellbeing (improving or restoring physical function)
1. WEINREB, NJ. et al. Am J Hematol 2008; 83(12): 896–900.
2. GRABOWSKI, GA. Lancet 2008; 372: 1263–71
3. MEHTA A. Eur J Int Med. 2006; 17:S2–S5.

Enzyme Replacement Therapy

ERT for Gaucher disease is designed to replace a specific defective or missing lysosomal enzyme (β-glucocerebrosidase), as shown in the figure below.1 The replacement enzyme helps break down the glycosphingolipid substrate thereby preventing accumulation of the storage material and subsequent tissue damage.1,2

1. KOLTER, T and SANDHOFF, K. Biochimica et Biophysica Acta. 2006;1758:2057–79.1.
2. LUTSKY, KF and TEJWANI, NC. Bulletin of the NYU Hospital for Joint Diseases. 2007;65:37–42.

Substrate Reduction Therapy

SRT is an approach used to treat LSDs by inhibiting the synthesis of substrate and subsequent influx into the lysosomes, as shown in the figure below.1 In Gaucher disease, SRT reduces the rate of glycosphingolipid substrate production and thus lysosomal accumulation.

1. KOLTER, T and SANDHOFF, K. Biochimica et Biophysica Acta. 2006;1758:2057–79.

Symptomatic Treatment

Supportive care to alleviate symptoms of Gaucher disease is an integral part of disease management, and should be provided by a multidisciplinary team with expertise in Gaucher disease.1

Treatment of bone manifestations is mostly directed at the prevention of irreversible complications.2 For example, patients with cases of osteopenia or osteoporosis may be treated with bisphosphonates and calcium/vitamin D.1,3,4

Orthopaedic surgery may be necessary in cases of pathologic fractures or avascular necroses. Bone pains or bone crises may be treated with bed rest, analgesics and oral prednisolone.3,4
Anemia may require blood transfusions after confirmation of no iron or vitamin B12 deficiency.1,3
Supportive care to alleviate symptoms of Gaucher disease is an integral part of disease management, and should be provided by a multidisciplinary team with expertise in Gaucher disease.1

A tendency to bleed indicates abnormalities in platelet count and function, and coagulation factors, potentially requiring platelet transfusions and other appropriate preparations before surgical procedures or pregnancy.1,3,4
Once popular, splenectomy is now performed only in cases of severe thrombocytopenia or symptomatic organomegaly that are unresponsive to ERT.1,3,4
Liver transplants are rarely necessary today, but may be considered in cases of progressive liver fibrosis, portal hypertension, and cirrhosis.3,4
Neuronopathic disease is best managed by a neurologist, and using specific drugs such as those indicated for seizures and symptoms of Parkinsonism. Malignancies should be referred to the appropriate oncologist for therapy.1,3

1. PASTORES, GM and HUGHES, DA. Gaucher Disease. 2000 Jul 27 [Updated 2015 Feb 26]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015. Available from:
2. Genzyme Europe B.V. Cerdelga® Summary of product characteristics, 2015. Available at:
Accessed September 2015.
3. NAGRAL, A. J Clin Exp Hepatol. 2014;4(1):37–50.
4. JMOUDIAK, M and FUTERMAN, AH. Br J Haematol. 2005;129:178–88.
Assessing Quality of Life in Clinical Practice: A Physician’s Perspective – Dr Gregory Pastores

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