Treatment with Cerezyme (imiglucerase), Sanofi Genzyme‘s enzyme replacement therapy, can effectively reverse severe pulmonary and liver complications triggered by Gaucher disease, a case report suggests.
The study “Reversal of life-threatening hepatopulmonary syndrome in Gaucher disease by imiglucerase enzyme replacement therapy” was published in the journal Molecular Genetics and Metabolism Reports.
In Gaucher patients, defects in the glucocerebrosidase enzyme — which degrades a fat molecule called glucocerebroside — results in some cells build up too much of this fat. These cells – called Gaucher cells – then travel to organs like the liver, spleen, and bones, causing common Gaucher symptoms like spleen and liver enlargement and bone fractures.
The liver is affected in virtually all Gaucher patients. Some have only mild liver enlargement, but others develop massive livers, along with elevated liver enzymes and cirrhosis. These people are at a higher risk for liver cancer, even when the liver is not cirrhotic.
In extreme cases, patients also develop severe complications in their lungs, affecting oxygen transfer to the body and causing severe shortness of breath, a condition called hepatopulmonary syndrome (HPS). Because no therapies are known to reverse HPC, these people usually undergo a liver transplant.
Researchers in Egypt and the U.S. described the case of a Gaucher patient whose lung (HPS) and liver disease were dramatically reversed with Cerezyme treatment.
The girl had her spleen removed at the age 3 after it was found to be massively enlarged, and she developed anemia and low platelet levels. Following the spleen’s removal, her symptoms eased, but her liver kept progressively enlarging, eventually occupying her entire abdomen at age 10.
She became increasingly short of breath, and showed changes in her fingers that suggested low oxygen supply.
A liver biopsy showed a massive infiltration of Gaucher cells and that the organ had become cirrhotic, meaning it was so damaged it wasn’t functioning properly. Along with a mutation in the GBA gene, this confirmed a diagnosis of Gaucher disease.
Between age 10 and 14, the girl developed HPS, chronically low oxygenation, and massive liver enlargement. Given the severity of her symptoms, the 14-year-old started treatment with Cerezyme, provided through a humanitarian program established by Project Hope and Sanofi Genzyme.
Treatment brought significant improvements in her symptoms, including a reduction in liver size, increases in hemoglobin and platelet levels, and better oxygenation. Her growth failure and finger clubbing also stopped and normalized with Cerezyme use.
Importantly, significant respiratory improvement also accompanied treatment, although the lungs often do not benefit from enzyme replacement therapy due to their high uptake by other organs. Researchers suggest that the lungs were able to claim more of Cerezyme’s effects because the spleen had been removed years earlier.
“The dramatic effects of [Cerezyme] seen in our patient is likely due to primary reversal of liver disease and hepatic fibrosis with additional effect on pulmonary vascular macrophages [infiltrated cells],” the researchers wrote.
The association between severe tissue scarring and Gaucher’s disease is not fully understood, and future studies should focus on exploring the underlying mechanisms of “widespread response to the metabolic defect in Gaucher disease involving the liver, bone marrow, spleen, and the lungs,” the scientists suggested.