Gaucher disease: unmet treatment needs.
Gaucher disease is a multisystemic metabolic disorder arising from a deficiency of lysosomal glucocerebrosidase. The predominant clinical manifestations of the disease are hepatosplenomegaly, peripheral blood cytopenias and skeletal disease. Treatment with enzyme replacement therapy (ERT) and substrate reduction therapy (SRT) has been shown to be effective in improving organ volume, anaemia, thrombocytopenia, bone markers and biomarkers in patients with Gaucher disease. However, some patient needs remain unmet because of the limited availability of treatment, the inaccessibility of certain disease sites and emerging disease manifestations. An increase in haematological, lymphoreticular and immune system malignancies has been observed in patients with Gaucher disease, but mechanisms underlying the development of these are not fully understood. Mild neurological manifestations may also affect patients with type 1 Gaucher disease, but treatment with ERT or SRT does not improve neurological function. Potential new treatments for Gaucher disease include small molecules, which may penetrate tissues that are not accessible by ERT.


CONCLUSIONS
ERT currently remains the most effective treatment for Gaucher disease. New treatments are emerging, but deficiencies in understanding basic pathophysiological mechanisms hinder progress.
Mehta
Atul
A
Lysosomal Storage Disorders Unit, Department of Haematology, Royal Free Hospital and University College Medical School, London, UK. atul.mehta@royalfree.nhs.uk
D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005776:Gaucher Disease / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology / Q000628:therapy*; D005962:Glucosylceramidase / Q000627:therapeutic use; D065089:Glycoside Hydrolase Inhibitors; D006297:Health Services Accessibility; D019337:Hematologic Neoplasms / Q000209:etiology; D006801:Humans; D007719:Knee Joint / Q000473:pathology; D008279:Magnetic Resonance Imaging; D011994:Recombinant Proteins / Q000627:therapeutic use
D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D011994:Recombinant Proteins; D017485:1-Deoxynojirimycin; C059896:miglustat; D005962:Glucosylceramidase; C090568:imiglucerase