How FLT-200 works
Gaucher disease is a heritable genetic disorder that can affect many organs and tissues. The disease is caused by mutations in the GBA gene, which provides the instructions to make an enzyme called beta-glucocerebrosidase. This enzyme is responsible for breaking down a cellular waste product called glucocerebroside. Mutations in GBA cause the enzyme to be made incorrectly; the faulty enzyme is unable to break down glucocerebroside, which builds up to a toxic level within cells.
FLT-200 uses an adeno-associated viral vector to deliver a normal copy of the GBA gene to cells. Once within the cells, the GBA gene is inserted into the genome and is used by the cell to make the normal beta-glucocerebrosidase enzyme. FLT-200 carries a signal that makes the gene active only in the liver, allowing the liver to potentially produce enough normal enzyme to control the symptoms of Gaucher disease.
However, this type of approach is very new and in early stages of development. Researchers are working on determining the right “dosage” of virus needed to treat Gaucher disease and ensure that cells do not produce too much of the enzyme. Moreover, research on this and other gene therapies has yet to determine whether one treatment will be sufficient, and if not, how frequently the treatment will need to be administered.
FLT-200 in research
The results of a preclinical study of a gene therapy similar to Freeline’s proprietary viral platform were published in the Journal of Gene Medicine. The study used a mouse model of Gaucher disease treated with GBA gene therapy delivered by a virus. Mice treated with the virus prior to the development of Gaucher symptoms were prevented from accumulating glucocerebroside and did not develop Gaucher-type cells (cells showing damage typical of Gaucher disease) in the liver, spleen, and lungs. In older mice with established disease symptoms, the treatment normalized glucocerebroside levels in the liver and the spleen, and significantly reduced accumulation in the lungs. The authors concluded that gene therapy may be a potential treatment for Gaucher disease.
Freeline presented its own preclinical findings in early 2019 at the 15th Annual WORLD Symposium. A single injection of FLT-200 resulted in a steady increase in beta-glucocerebrosidase levels in the blood of a mouse model of Gaucher disease. The researchers further reported that the enzyme was taken up by the spleen, lungs, and bone marrow, all organs and tissues affected by Gaucher disease.
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