Gaucher Disease

Gaucher disease (GD) is a rare, autosomal recessive, inherited disorder in which toxic levels of the fatty substance (lipid) glucocerebroside accumulate in cells. GD affects one in 50,000 individuals worldwide. 

There are three types of GD, and the phenotypes range from a lethal perinatal to asymptomatic:

1. Type 1 is characterized by accumulation in spleen, liver, and bone marrow results in enlarged liver and spleen, anemia, bone pain and fractures, and lung disease, manifests in childhood or in adults. The CNS is not affected
2. Type 2 (acute or infantile), the central nervous system is affected; the age of onset is less than two years of age, and the central nervous system is affected. The disease is characterized by limited psychomotor development; the disease progresses rapidly and can be fatal between two and four years of age
3. Type 3 (sub-acute or juvenile), the central nervous system is affected; the age of onset is less than two years of age. The disease progresses less rapidly than Type 2; individuals affected by GD Type 3 tend to live into their 30s and 40s 

In addition to the above types, there are two other subtypes:

1. Perinatal-lethal: this subtype is characterized by skin abnormalities or nonimmune hydrops fetalis
2. Cardiovascular: this subtype is characterized by calcification of heart valves, mile splenomegaly, corneal opacities, and supranuclear ophthalmoplegia (eye movement disorder)

GD is caused by low levels of glucocerebrosidase (GCase), an enzyme required to break down glucocerebroside, due to mutations in the GBA gene encoding GCase. Undegraded glucocerebroside and related compounds accumulate in scavenger macrophages/monocytes forming characteristic Gaucher cells in liver, spleen, and bone marrow.

Currently available treatments that address GCase enzyme deficiency and glucocerebroside accumulation include:

1. Enzyme replacement therapy (ERT)
2. Substrate reduction therapy (SRT) for select individuals affected by GD
3. Multiple investigational products in development, including gene therapy 

M6PT is exploring potential gene therapy products and ERT options to treat individuals with GD.