Gene therapy tackles the source of disease in the patient’s DNA through viral or bacterial vectors. Most commonly, muscle cells are targeted because muscle injection is an accessible entrance to the body. However, muscle cells may not be capable of producing the right protein. A recently published study explores how changing protein regulation networks can enhance muscle cells’ ability to respond to gene therapy.
AAT deficiency is a condition in which liver cells produce insufficient quantities of the protein AAT. Consequently, serious respiratory problems can develop, such as COPD or emphysema. Common treatment involves regular hospital trips for infusion or investment into expensive home equipment. However, Dr Terence Flotte developed an injectable AAT gene therapy that allows sustained AAT release over several years. Unfortunately, he found that because muscle cells can’t produce the AAT proteins, the increase after gene therapy was limited.
The recent study explored the options for transforming muscle cells into better protein production sites, like liver cells. They tested several on mice muscle cells to see if they would boost AAT secretion and found that adding suberoylanilide hydroxamic acid (SAHA) enables this. In the future, the hope is that using SAHA or similar proteostasis regulators to gene therapies would ameliorate treatments for genetic diseases.
This study has “implications beyond just gene therapies”, according to Professors Daniel Hebert and Lila Gierasch. They believe that mRNA vaccines, which work according to cell production of proteins, “face the same limitations as gene therapies”.
“Increasing the protein production of muscle cells could potentially improve vaccine immunity.”
Furthermore, lots of drugs are derived from natural sources and “rely heavily on a given cell’s protein production capabilities”. Professors Hebert and Gierasch think that a protein homeostasis enhancer could “optimise protein yield and increase the effectiveness of the drug”. This would have implications beyond drug development, for neurodegenerative diseases, for example. They look forward to further research on “ways to improve the cellular machinery” to “open many new doors” against a range of diseases.
To hear from industry leaders at the World Vaccine Congress in Europe, 2022, head to this page to buy tickets.