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Lysosomal Storage Diseases
Lysosomal storage diseases (LSDs) comprise a large group of rare inherited disorders, including Tay Sachs Disease, Fabry Disease, Gaucher’s Disease, Pompe Disease, Nieman Pick, Hunter syndrome and other mucopolysaccharidosis (MPS).
LSDs arise from enzyme deficiency resulting from inherited gene mutations. Specifically, the enzymes involved are required for metabolism of lipids or glycoproteins within cells; accumulation of these molecules within the cell lysosome underlies the pathology of the disease.
Each LSD is associated with reduced or ablated expression of a different protein, and exhibits symptoms arising from different organs. Many of these diseases are evident in infancy or childhood, however, some appear later in life.
As a group, LSDs occur with incidences of about one in every seven thousand births. While there are no cures for LSDs, intravenous delivery of the deficient enzyme (enzyme replacement therapy, ERT) has been used to ameliorate symptoms in patients with some LSDs.
Currently available ERTs do not cross the blood-brain barrier (BBB); therefore, neurological symptoms, such as cognitive decline and behavioral changes, have not been addressed by ERT.
Hurler Syndrome (MPSI)
Hurler syndrome, one of the most severe LSDs, also known as mucopolysaccharidosis type I (MPS I), is a genetic disorder that results in the deficiency of alpha-L-iduronidase (IDUA), an enzyme responsible for the degradation of mucopolysaccharides in lysosomes. Without this enzyme, glycosaminoglycans build up and damage organs.
Using its platform technology, Angiochem is designing and testing new enzyme derivatives by conjugating Angiopep-2 to IDUA so that they will not be easily cleared by the liver, will increase brain penetration to be used for ERTs for the treatment of Hurler syndrome (MPS I). Lysosomal enzymes have a short half-life and are rapidly cleared in the liver. If not protected by structural modifications, they will be cleared before even reaching the BBB. Once an Angiopep-2 enzyme conjugate gains entry into the brain, it has to be designed to gain entry into the lysosomes while keeping their enzymatic activity.
In addition to discovery work done internally, Angiochem is also working with partners to discover and develop new treatments for LSDS. For more information Angiochem’s collaborations in LSDs, browse Partnering section.