Dr Joseph HorriganJoseph Horrigan, MD
A new clinician-rating scale to assess features of congenital myotonic dystrophy type 1 (CDM1), dubbed the Clinician-Completed Congenital Myotonic Dystrophy Type 1 Rating Scale (CDM1-RS), has been presented by AMO Pharma at the Muscular Dystrophy Association (MDA) Clinical & Scientific Conference in Orlando, Florida.1

Joseph Horrigan, MD, the company’s chief medical officer and the presenter of the scale, called its development a “major milestone for researchers looking to enhance our understanding of this disorder,” in a statement. Ultimately, scale recognizes 11 observable characteristics of CDM1, rating each on a 4-point Likert scale. It was developed with insight from the experiences of patients and caregivers, therapeutic area experts, and advice from the FDA.

"We look forward to broadening the scope of this scale so that we may better address the current and future needs of this largely underserved community,” Horrigan added.

Patients with CDM1 often experience symptoms—cognitive and critical thinking challenges, speech impairment, muscle weakness, and autism-type symptoms—shortly after birth, and are treated with a combination, symptom-based approach. There are no available treatments for the estimated 3500 to 16,000 patients.2-3

"Standard assessment tools should be used to follow FDA guidance and capture all of the characteristic symptoms of a condition to be useful in clinical trials. To that end, the CDM1-RS rating scale has been evolved from the well-validated MDHI and CCMDHI measures developed by professor Chad Heatwole and professor Nicholas Johnson in the hope it can become a widely accepted clinician instrument for CDM1," said Michael Snape, PhD, chief executive officer of AMO Pharma.

The scale is expected to serve as the primary outcome measure in AMO Pharma’s upcoming phase 2/3 trial in children and adolescents with CDM1, which will evaluate the company’s investigational agent tideglusib, also known as AMO-2 (NCT03692312). Tideglusib is an orally available, small-molecule thiadiazolidinone class medication. It is a glycogen synthase kinase 3 (GSK3-β) inhibitor.

Previously, results of a phase 2 trial tideglusib suggested that the treatment is associated with improvements in cognitive function, fatigue, and neuromuscular symptoms in myotonic dystrophy type 1 (DM1). A 1000-mg dose of the  GSK3-β inhibitor rendered a clinical benefit for the majority of patients after a 12-week treatment period, and 4 of the 10 efficacy variables assessed—including grip strength, Clinician Visual Analogue Scale rating, Caregiver Top 3 Concerns rating scale, and Ohio State University Clinical Global Impression of Improvement rating scale—differed in favor of the 1000-mg dose over the 400-mg dose, with no worsening in the remaining 6 variables.4

"The availability of scale to assess CDM1 can expand our understanding of this disorder, streamline the diagnostic process and could provide essential insights to guide future clinical research," Snape said.
REFERENCES
1. AMO Pharma Announces Launch of First Clinician-Completed Rating Scale for Congenital Myotonic Dystrophy Type 1 [press release]. London and Durham, NC: AMO Pharma Limited; Published April 16, 2019. prnewswire.com/news-releases/amo-pharma-announces-launch-of-first-clinician-completed-rating-scale-for-congenital-myotonic-dystrophy-type-1-300832367.html. Assessed April 16, 2019.
2. Wesstrom G, Bensch J, Schollin J. Congenital myotonic dystrophy. Incidence, clinical aspects and early prognosis. Acta Paediatrica Scandinavica. 1986;75:849–54.
3. Gonzalez de Dios J, Martinez Frias ML, Egues Jimeno J, et al. Epidemiological study of Steinert’s congenital myotonic dystrophy: Dysmorphological characteristics. Anales Espanoles de Pediatria. 1999;51:389–96.
4. Snape M. The utility of concordant trend analyses in a phase 2 study in congenital andchildhood onset myotonic dystrophy type 1: a case example. Presented at: 7th International Conference on Neurology and Neuromuscular Diseases; Madrid, Spain; October 23, 2018. neuromuscular.pulsusconference.com/2018/abstract/the-utility-of-concordant-trend-analyses-in-a-phase-2-study-in-congenital-and-childhood-onset-myotonic-dystrophy-type-1-a-case-example. Accessed April 16, 2019.