Pompe disease is a lysosomal storage disorder where glycogen accumulates in cell structures called lysosomes, bags of about 50 different enzymes surrounded by a membrane similar to the cell membrane, which function as the digestive system for the cell.

What happens in Pompe disease?

In Pompe disease, lysosomes do not contain enough of an enzyme called acid alpha-glucosidase (GAA.) This enzyme is necessary to break down glycogen — a complex sugar molecule — into glucose, the simple sugar that the body uses for energy. If glycogen is not broken down, it builds inside cells and causes damage.

In addition to this essential process, lysosomes may  also fuse with the cell membrane to move bulk contents like proteins out of the cell — a process called exocytosis.

Lysosomal exocytosis as potential treatment

Researchers recently discovered a network of genes and two transcription factors (proteins that regulate the production of other proteins) that control lysosomes and their function.  They found that increased levels of these two transcription factors, TFEB and TFE3, could induce exocytosis by lysosomes. Building on this discovery, they hypothesized that if a way could be found to stimulate exocytosis in Pompe disease patients, it might reduce the buildup of glycogen inside patients’ cells.

Experiments were done in mice genetically altered to have a condition that mimicked Pompe disease. Researchers found that increasing the activity of TFEB in these mice caused lysosomes in muscle cells to move their glycogen out of cells, reducing the damaging amount of glycogen accumulation.

Artificially stimulating lysosomal exocytosis is still in early, pre-clinical stages of development, meaning this potential treatment approach has not been tested in humans. But ongoing research into this new approach could lead to a new way of treating Pompe disease.

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