Clinical trials are important to understanding both more about certain conditions and more about the safety, efficacy, and tolerability of drugs designed to treat these conditions. Currently, biopharmaceutical company AMO Pharma Ltd. (“AMO”) is enrolling patients for the Phase 3 REACH-CDM X study to evaluate AMO-02 (tideglusib) for congenital myotonic dystrophy (DM1). According to a September 30 news release, the first patient finished the REACH-CDM clinical trial and is now enrolled in the next step of the study: REACH-CDM X.

AMO-02

To begin, let’s take a look at AMO-02 and what it actually is. According to AMO:

In cellular and animal models of DM1 as well as in muscle biopsies from patients, activity of glycogen synthase kinase 3 beta (GSK3ß) has been shown to increase. AMO-02 is an inhibitor that has been shown to normalise levels of GSK3ß in transgenic models and in ex vivo tissue samples in patients with DM1 and to reduce levels of the mRNA that is pathogenic for DM1.

Outside of exploring AMO-02 for congenital DM1, AMO also believes that the therapy could have benefits for other neuromuscular and central nervous system (CNS) indications.

Now, researchers are exploring AMO-02 for congenital DM1 within the open-label REACH-CDM X extension study. Patients who complete the prior study are eligible to move over to the open-label study. During this, they will receive AMO-02 treatment for a 12-month period. Altogether, 56 patients will enroll. Researchers hope to learn more about:

• Safety and efficacy regarding long-term AMO-02 treatment
• How well AMO-02 benefits children and adolescents with congenital DM1
• Whether treatment improves muscle function and other symptoms

Myotonic Dystrophy

There are two forms of myotonic dystrophy, a rare disease characterized by muscle wasting and weakness: types 1 and 2. Both forms are caused by genetic mutations. For example, the DMPK gene having an abnormally expanded section results in DM1, while an abnormally expanded section on ZNF9 causes DM2. Both cases have overlapping symptoms. However, DM1 is often more severe and has a worse prognosis than DM2. There are also subsets within each category. According to the National Organization for Rare Disorders (NORD), DM1 can be mild, classic, or congenital. The congenital form is often the most severe form.

Patients with myotonic dystrophy are unable to relax certain muscles after use and undergo myotonia, or prolonged muscle contractions. Some symptoms of myotonic dystrophy include:

• Voluntary muscle weakness
• Myotonia
• Abnormal heart rhythm
• Heart and breathing muscle weakness
• Difficulty breathing and swallowing
• Constipation
• Gallstones
• Labor and pregnancy complications
• Cataracts
• Problems with hearing, vision, and speech
• Cognitive impairment
• Learning disabilities

Since the above article covered a trial around congenital DM1 in particular, I also want to go a little more in-depth into congenital DM1-specific symptoms. These include:

• Severe muscle weakness
• “Floppy” muscle tone
• Facial diplegia (muscle weakness on both sides of the face)
• Learning and behavioral disabilities
• Astigmatism or farsightedness (other vision abnormalities may occur)
• Failure to thrive
• Gastroparesis
• Clubfoot
• Nausea
• Respiratory failure
• Cardiac abnormalities

Learn more about myotonic dystrophy.