Efficiency of Pompe Disease Treatment Improved by Molecular “Tag”

By Jodee Redmond from In the Cloud Copy

The results of a recent study published in Pompe Disease News suggest that a molecular “tag” used to improve the distribution of the acid-alpha-glucidodase (GAA) protein to cells improved the efficiency of gene therapy in mice being treated for Pompe disease.

What is Pompe Disease?

Pompe disease is a genetic disorder caused by an accumulation of a particular complex sugar called glycogen in the body’s cells. When glycogen accumulates in the body’s tissues and organs (especially muscles), their ability to function normally becomes impaired.

GAA is the protein that normally breaks down glycogen (a complex sugar) into a simpler version (glucose). In a person with Pompe disease, this ability is limited or may even be shut down completely.

Gene Therapy a Treatment Option for Pompe Disease

One proposed treatment option is gene therapy. It works by giving the body back its ability to produce the GAA enzyme on its own. To accomplish this goal, cells are provided with a functioning copy of the GAA gene.

To deliver the functioning copy of a gene, a modified virus is usually used as a vector. This is called an adeno-associated virus (AAV). A vector is a way to transport the gene into the cells.

An AAV vector doesn’t work as a standard virus. It doesn’t have any dangerous properties that will cause the recipient to get sick, as these have been removed. The desired gene is added (in the case of a patient with Pompe disease, GAA). Like a virus, it integrates the gene into the patient’s cells, providing the patient with a new, healthy copy of GAA.

Gene therapy can be targeted toward specific tissues in the body. For example, some patients have difficulty breathing. In that instance, the GAA can be targeted to the diaphragm to help improve breathing capacity.

GILT Tag Added to GAA Protein

The researchers involved in the new study created a form of gene therapy that delivered directions for a GAA protein with a molecular “tag.” This was called a glycosylation-independent lysosomal targeting (GILT) tag.

The GILT tag is a tiny update to the GAA protein that is identified by other proteins in a cell. This addition makes the GAA transport process to the lysosome easier.

The researchers then compared the gene therapy encoded, GILT-tag modified GAA to the encoded unmodified GAA in the tongues of mice with Pompe disease. They were able to confirm that both therapies successfully increased GAA expression in the animals’ tongues.

In this early stage of research, it’s important to continue to focus on the fact that the study was carried out on mice. It’s impossible to tell at this stage whether these results will have a bearing on possible treatment options for humans with Pompe disease in the future. The gene therapy was delivered by injection to the tongue only, and this was the only part of the body examined. The researchers noted that different means of administering the therapy may have to adopted to make it effective in human patients.


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