Towards more effective enzyme replacement therapy for inherited and acquired Lysosomal Storage Diseases of muscle tissue.

01 January 2017 → 31 December 2020
Research Foundation - Flanders (FWO)
Research disciplines
No data available
Biopharmaceuticals Glyco-Engineering Lysosomal Storage Diseases
Project description

Breakdown of waste compounds in our cells is essential for their long-term viability. However,
when people have a mutation in a gene that code for an enzyme that facilitates the degradation
process or when people age, waste products are not removed very efficient anymore. One group
of such diseases is called Lysosomal Storage Diseases (LSD). This results in an accumulation of
these waste compounds in the lysosomes of cells. A therapy has been developed for LSD which
concerns an intravenous injection of a functional equivalent of the deficient enzyme: Enzyme
Replacement Therapy (ERT). In that way, the active form is able to degrade the stored products in
diseased cells. Besides the genetic variants, also acquired LSD exist in nature. Those are caused by
an accumulating substrate especially due to aging. We believe that the concept of ERT can be
expanded towards these acquired diseases. The goal of the project is to recombinantly produce
Acid Alpha-Glucosidase and Cathepsin D, two enzymes that can treat Pompe Disease (genetic LSD)
and Inclusion Body Myositis (acquired LSD). In both diseases, the skeletal muscles are affected.
Therefore both enzymes will be fused to a Nanobody that recognizes receptors on those muscle
cells. Moreover, the fused molecules will be recombinantly produced in GlycoDelete cells. Within
these cells, sugars on proteins are trimmed which makes the proteins less sensitive for clearance
by the liver and will lead to enhanced delivery to muscle cells.