Glycolipids are a diverse class of bioactive molecules that function in a variety of normal and pathogenic cellular processes. Genetic defects in the enzymes that metabolize different glycolipid can lead to their abnormal accumulation of lipids in lysosomes of different cell types. This accumulation can have a variety of pathogenic effects and lead to a collection of diseases called lysosomal storage diseases (LSD). Depending on the severity and the specific glycolipids involved, these LSDs can impact various body organs including heart, kidney, liver and in some cases the central nervous system.
By inhibiting the enzymes that synthesize these glycolipids, we target the root cause of the diseases by decreasing the production of the pathogenic glycolipids. This approach is called substrate reduction therapy (SRT). AceLink is developing both brain-targeting and non-brain-targeting small molecule therapeutics to treat different lysosomal storage disorders. Some examples of LSDs that can be treated with SRT are Fabry disease, Gaucher disease, and GM1 and GM2 gangliosidosis.
Glycolipids are also dysregulated in chronic non-genetic diseases where they contribute to disease associated inflammation, cell proliferation, protein misfolding, and fibrosis. These diseases include polycystic kidney disease, diabetic kidney disease, fatty liver disease, heart disease, and even Parkinson’s disease. For these non-genetic diseases, reducing the cellular levels of specific glycolipids can also be therapeutic.