Gaucher Disease: “Rare Disorder with High Unmet Needs”

Gaucher Disease is a rare autosomal recessive inherited multisystem disease with phenotypic variation from mild to very severe. It is the most common lysosomal storage disorder which occurs due to the deficiency of an enzyme β-glucocerebrosidase that helps in degrading glucocerebroside into glucose and ceramide. Lack of degradation of glucocerebroside into glucose and ceramide results in accumulation of glucocerebroside within the lysosomes.

Gaucher Disease is classified as Type 1 Gaucher Disease, Type 2 Gaucher Disease, and Type 3 Gaucher Disease on the basis of symptoms and course of the disease. The treatment of Gaucher Disease apart from the Enzyme Replacement Therapy and Substrate Reduction Therapy is not very encouraging as there is no approved therapy for the treatment of Type 2 Gaucher Disease, and Type 3 GD.

Enzyme Replacement Therapy has been proven safe and effective for a period of over 14 years, by reducing clinical symptoms. Several limitations such as the requirement of life-long, intravenous infusions at least once every two weeks and its inability to cross the blood-brain barrier are associated with the use of Enzyme Replacement Therapy. Several studies have demonstrated that Enzyme Replacement Therapy is not effective for the treatment of Gaucher Disease patients with neuropathic involvement (Type 2 & Type 3 Gaucher Disease) and severe or pre-existing bone and lung lesions.

Although the introduction of Substrate Reduction Therapy has overcome the few limitations of the existing Enzyme Replacement Therapy as Substrate Reduction Therapy provides a consistent dose over time and Zavesca can crosses the blood-brain barrier. Substrate Reduction Therapy is not recommended for the children, pregnant or breastfeeding women, elderly patients, and patients with severe kidney or liver disease.

The unmet need also remains high due to the limited availability of existing therapy, inaccessibility of certain disease sites such as Central Nervous System (CNS) and, to a lesser extent, bone and lungs and emerging disease manifestations such as malignancy and neurological changes. Therefore there is an immense need for improving the existing therapies for the treatment of GD.

Lack of understanding regarding the basic pathophysiological mechanisms of GD is hindering the progress of developing effective therapies for Gaucher Disease. The pipeline of Gaucher Disease is not robust as there are few drugs in late clinical phase and a large number of drugs are present in Pre-Clinical and Discovery stages which will take approximately 15- 20 years to reach the market.

Therefore, unmet treatment needs are likely to remain for the foreseeable future. Research related to the complex pathophysiology of GD for the development of pharmacological effective therapies would provide some ray of hope to patients with GD for improving their quality of life.

Insight by:
Diksha Wadhwa