Using plant-made enzymes to treat and diagnose lysosomal storage diseases
When we’re healthy, the lysosome of our cells plays a key role in our body’s recycling system by breaking down large carbohydrate molecules and passing them on to other parts of the cell.
In those with lysosomal storage diseases (LSDs), however, these carbohydrates are not broken down and are caught in the lysosome, eventually killing the cell and leading to disease symptoms.
“It is the equilibrium between breakdown and biosynthesis that really keeps cells healthy and happy. When an enzyme deficiency occurs, these complex carbohydrates accrue in patient cells, and they cause the disease process,” says Dr. Lorne Clarke, a researcher at the University of British Columbia. Clarke is an investigator working on this project along with project leader Dr. Allison Kermode (Simon Fraser University).
While there are treatments for these diseases, Clarke and Kermode have harnessed the power of plants for a potentially more effective treatment option. Most lysosomal storage diseases, including the childhood metabolic disease Mucopolysaccharidosis I (MPS I), are caused by an enzyme deficiency – in the case of MPS I, the enzyme is called iduronidase.
A typical strategy to combat this deficiency is to generate the enzyme using cell cultures and then administer it to patients in a process called enzyme replacement therapy (ERT). However, ERT is costly and not always effective.
But Kermode and Clarke have found that by using plants as hosts to produce the iduronidase enzyme, they can stimulate enzyme production rapidly and in a more cost-effective manner. In addition, the plant cells are not subject to contamination from pathogens that affect humans, making them safer.
“The prospect of creating a therapeutic enzyme for ERT administration in patients is reaching a fruitful stage, where we are starting to look at therapeutic efficacy. Once completed, we can begin to scale up the purification of our enzyme target and develop the means to get it into clinical trials,” Kermode adds.
Early detection of the disease is critical to impacting outcomes for patients, and so newborn screening is also essential. “We are at an exciting phase where we can market the iduronidase enzyme created with our plant host system for use as a screening reagent,” says Kermode.
“The potential outcomes of our research are two-fold: one is to create cost-effective enzyme therapeutics for MPS I and other lysosomal storage diseases, and the second is to use the plant-made enzyme target as a reagent in newborn screening for LSDs,” says Kermode.