Technology Transfer Department

Application sectors

Problem to solve

Currently, there is no effective cure for Glycogen Storage Disease type III, a rare genetic disorder caused by deficiency of the glycogen debranching enzyme (GDE), leading to abnormal glycogen accumulation in muscle, heart, and liver. This technology delivers plasmid DNA encoding GDE into affected tissues via pulsed electric fields (EGT) and/or nanoparticles. The non-viral approach is safe, repeatable, and overcomes the limitations of viral vectors, with potential applications in other rare and common genetic diseases.

Description

Glycogen Storage Disease type III (GSDIII) is a rare genetic disorder caused by a deficiency of an enzyme involved in glycogen metabolism. The condition is due to a genetic mutation that impairs the production of the glycogen debranching enzyme (GDE), leading to the abnormal accumulation of glycogen, particularly in the liver, heart, and skeletal muscles. Symptoms typically appear in early childhood and include liver enlargement, hypoglycemic episodes, and growth delay. As the disease progresses with age, it may lead to more severe manifestations such as muscle weakness, cardiomyopathy, and reduced quality of life. Currently, there is no curative treatment for GSDIII: the only approach is a strict and continuous diet aimed at maintaining stable blood glucose levels. However, this does not address the underlying cause of the disease and does not stop its progression. The proposed innovation directly addresses the genetic defect underlying GSDIII. A plasmid has been developed containing the instructions to produce the missing enzyme in its active form. This DNA can be delivered into the cells of affected tissues—particularly muscles and liver—using physical or chemical methods, such as controlled electric pulses (electro gene transfer) or nanoparticles. Once transferred, the DNA enables the cells to synthesize the missing enzyme, thus restoring the impaired function. This is a non-viral strategy, safer than traditional virus-based methods and potentially repeatable over time. The approach has shown efficacy in animal models and is designed to be applicable to other similar genetic diseases as well.

Research group involved