Most ERTs are administered to patients via infusion. The ERT enzyme then needs to make its way from the bloodstream to the lysosomes within the affected cells to help metabolize the accumulating lipids, carbohydrates, or proteins. Mannose 6-phosphate (M6P) is a specialized carbohydrate structure found on the surfaces of lysosomal enzymes, and it enables ERT enzymes to bind to specialized M6P receptors on cell surfaces. Once this happens, the ERT enzymes can reach the lysosomes and exert their biological functions. Without M6P, ERT enzymes cannot make their way into the lysosomes to metabolize the accumulating substrates.
Since M6P is required to deliver ERT enzymes to lysosomes, increasing the M6P content of therapeutic enzymes is a logical strategy to improve lysosomal targeting for ERTs. However, it is extremely difficult to control carbohydrate processing to create ERT enzymes with high amounts of M6P; it is virtually impossible to control carbohydrate processing in vivo using gene therapy..
Prior efforts to enhance M6P content have largely failed, despite decades of effort and hundreds of millions of dollars devoted to the endeavor. Consequently, most ERTs and gene therapy products do not reach the lysosomes where they are needed in sufficient quantities.
M6P Therapeutics developed a breakthrough technology platform in 2017 that enables the ability to create ERT enzymes with high levels of M6P.