Patient Input to Inform the Development of Central Nervous System Outcome Measures in Myotonic Dystrophy

Abstract

AbstractMyotonic dystrophy type 1 (DM1) and myotonic dystrophy type 2 (DM2) are multisystem, genetic disorders caused by repeat expansions on chromosome 19 (DM1) and chromosome 3 (DM2). Although the effects of DM on the skeletal, cardiac, and smooth muscles, as well as the endocrine and central nervous systems, can be disabling, there are no disease-modifying therapies for the disorder. Following a process established by the US Food and Drug Administration (FDA) in 2012 known as the Patient-Focused Drug Development (PFDD) Initiative, Myotonic (formerly the Myotonic Dystrophy Foundation) has been conducting patient- and caregiver-inclusive sessions to explore disease burden as defined by patients and caregivers, and what affected individuals want most from potential new therapies. In September 2017, at Myotonic’s annual conference, a session titled “Bringing the Patient Voice to CNS-Targeting Drug Development in Myotonic Dystrophy” attracted some 350 members of the DM community. During the session, patients and caregivers described CNS disease symptoms, their impact on quality of life, and potential CNS-related targets that they considered important for drug development consideration. These included fatigue and daytime sleepiness; dysregulated sleep; cognitive deficits such as “brain fog,” memory and focus impairment, learning and attention difficulties, and time management challenges; emotional/psychological/behavioral difficulties, including impulsivity, apathy, antisocial behavior, personality changes, and depression; social difficulties, including disconnection, lack of awareness, and feelings of isolation; and general anxieties about the future and potential loss of independence. Improvements in memory and lessening of “brain fog” were considered particularly important.