According to a relatively recent news release from biopharmaceutical company Maze Therapeutics, the company has begun dosing healthy volunteers in a Phase 1 clinical trial. During the trial, researchers are evaluating MZE001, a potential treatment option for late-onset Pompe disease.
What is MZE001? you may be asking. MZE001 is an orally administered glycogen synthase (GYS1) inhibitor. On the company’s website, Maze Therapeutics explains:
We believe a novel approach to treating Pompe disease is halting skeletal and respiratory muscle glycogen synthesis and its subsequent accumulation by inhibiting the action of the gene GYS1 through substrate reduction therapy, or SRT. High levels of accumulated glycogen are toxic to muscle and our GYS1 inhibitor has been shown to reverse that accumulation in preclinical models.
Within the Phase 1 clinical trial, researchers will seek to evaluate the therapy’s pharmacokinetic and pharmacodynamic profiles; safety; and tolerability. Additionally, the study seeks to build upon toxicity data from prior studies, which have shown MZE001 to be non-toxic and relatively safe for use.
About Pompe Disease
GAA gene mutations cause Pompe disease, a rare genetic disorder which affects an estimated 1 in every 40,000 Americans. These mutations, inherited in an autosomal recessive pattern, prevent the body from adequately processing glycogen. As a result, this complex sugar accumulates throughout the body and reduces muscle, tissue, and organ function.
Altogether, there are three major Pompe disease subtypes: classic infantile-onset, non-classic infantile-onset, and late-onset. As described above, MZE001 is being developed for the late-onset form. The breakdown of these subtypes is described below:
- Classic infantile-onset. Within this form of Pompe disease, symptoms appear within months following birth. Without treatment, classic infantile-onset Pompe disease can be fatal within the first 2-3 years of life. Symptoms associated with this subtype include an enlarged liver, muscle weakness, heart and breathing problems, and reduced muscle tone.
- Non-classic infantile-onset. Within this form, symptoms usually manifest by age 1, with the condition becoming fatal in early childhood. Associated symptoms include progressive muscle weakness and slowed muscle development. Unlike the classic form, heart failure is not typically associated with this subtype.
- Late-onset. Some medical professionals use “late-onset” to refer to any subtype in which the heart is not affected, rather than the age in which symptoms appear. However, typically, late-onset Pompe disease may cause symptoms to manifest anywhere from late childhood through adulthood. Similar to the non-classic infantile-onset form, this form does not usually affect the heart. In fact, the late-onset form is milder than the other two. Symptoms may include progressive muscle weakness and respiratory failure.
Learn more about Pompe disease.