GRO Biosciences’ ProGly platform shows promise in MG animal model
Treatment using specially made proteins found to ease disease severity
A treatment based on GRO Biosciences‘ ProGly program — which uses specially designed proteins to regulate the immune system — substantially reduced disease activity in an animal model of myasthenia gravis (MG), according to new data presented by the company.
“We are greatly encouraged by the results of [our] studies that clearly demonstrate both the therapeutic potential and the underlying mechanism of our ProGly [platform],” Daniel J. Mandell, PhD, CEO of GRO, said in a company press release.
ProGly platform aims to produce proteins with specific sugar molecules
The human immune system is responsible for defending the body against infections. Conceptually, its job is simple: it’s supposed to leave the body’s own healthy tissue alone, and attack anything that isn’t recognizable as such.
The ability of the immune system to recognize healthy tissues and cells is referred to as immune tolerance. Myasthenia gravis and other autoimmune disorders, which are caused by the immune system attacking the body’s own healthy tissue, are effectively a breakdown of tolerance.
Thus, finding ways to restore tolerance is widely viewed as a promising strategy for treating autoimmune disorders like MG.
GRO’s platform aims to induce tolerance for specific protein molecular targets that are attacked by the immune system in autoimmune diseases.
As an example, most cases of MG are driven by an immune attack against the muscle proteins acetylcholine receptor (AChR) or muscle-specific kinase (MuSK). This results in weakness and fatigue that can affect any muscles involved in the body’s voluntary movements.
All proteins in the body are made of building blocks called amino acids. There are 20 main amino acids that are put together into different combinations to make virtually every protein in the body.
The ProGly platform aims to produce proteins using non-standard amino acids (NSAAs) — in other words, amino acids that aren’t normally found in proteins produced in the body.
Specifically, the platform allows proteins to be produced with specific sugar molecules attached. These sugar molecules serve as a cue to the immune system that the protein is a normal part of the body, thereby helping to induce tolerance.
Company saw improvements in animal model of MG with treatment
According to GRO, a treatment based on the ProGly platform led to a “profound improvement” in an animal model of MG, helping to ease disease severity.
Data suggested that the ProGly-based treatment specifically led to the activation of regulatory T-cells, known as Tregs, primed to induce immune tolerance toward the molecular target used. Tregs are a specialized set of immune cells that prevent excess inflammation by other immune cell types and are also involved in immune tolerance.
GRO said data from other experiments showed its ProGly platform could be used to reduce the development of an immune reaction against enzyme replacement therapies, which are treatments used to manage genetic metabolic disorders in which people are not able to produce certain key enzymes.
While most patients develop an immune response against such treatment when the native protein is delivered, that response was dramatically reduced in animals when the enzyme was modified to include ProGly NSAAs.
“Getting patients off immunosuppressive therapies and preventing immunogenic responses to therapeutics are two of the greatest needs in our field,” said Tracey Lodie, PhD, scientific advisor to GRO and chief scientific officer of Quell Therapeutics, a London-based company developing Treg cell therapies.
Lodie added that the new data “represent a step-change in both applications that, if born out in the clinic, will revolutionize treatment for patients.”
GRO did not provide further details about these preclinical results or next steps for the development of the platform in its press release.
“With a clear development plan and a defined path to the clinic, we are closer to bringing these highly sought therapeutic capabilities to the patients who need them,” Mandell said.