Current enzyme replacement therapy for LSD is based on recombinant lysosomal enzymes synthesized with specific carbohydrate structures (mannose or mannose 6-phosphate). These carbohydrate groups are necessary for entry into target cells and elimination of storage materials in the cells. However, the recombinant enzymes may not always have the carbohydrate structures needed to target the cells of choice. Also, the carbohydrate structures do not guide the therapeutic enzymes through the blood-brain carrier due to the lack of complementary receptors. There is a need for a method of delivery that allows lysosomal enzymes to enter cells of choice, as well as cross the blood-brain barrier.

INNOVATION:  Researchers at UCLA have developed a method of delivering lysosomal enzymes to deficient cells to treat lysosomal storage disease. The delivery method uses conjugates of lysosomal enzymes and aptamers. Since lysosomal enzymes can be linked to aptamers, and aptamers can be selected against any desired target, lysosomal enzymes can now be delivered to areas that have not been reached.

POTENTIAL APPLICATIONS 

• Delivery of lysosomal enzymes to deficient cells for therapeutic purposes
• Treatment of neurological aspects of lysosomal storage diseases

ADVANTAGES

• Any lysosomal enzyme of interest potentially can be linked to an aptamer that is selected against any desired target
• It is possible to link aptamers linked to lysosomal enzymes without destroying enzyme activity
• Therapeutic enzymes can potentially enter into brain cells

DEVELOPMENT-TO-DATE:  Researchers have demonstrated the delivery of lysosomal enzymes and correction of substrate accumulation in cultured cells deficient in lysosomal enzymes.

Reference: UCLA Case No. 2008-128