Research Article: Gene therapy as a potential therapeutic option for Duchenne muscular dystrophy: A qualitative preference study of patients and parents

Date Published: May 1, 2019

Publisher: Public Library of Science

Author(s): Holly Landrum Peay, Ryan Fischer, Janice P. Tzeng, Sharon E. Hesterlee, Carl Morris, Amy Strong Martin, Colin Rensch, Edward Smith, Valeria Ricotti, Katherine Beaverson, Hannah Wand, Carol Mansfield, Ramesh Narayanan.


Duchenne muscular dystrophy (DMD) is a rare neuromuscular disorder that causes progressive weakness and early death. Gene therapy is an area of new therapeutic development. This qualitative study explored factors influencing parents’ and adult patients’ preferences about gene therapy.

We report qualitative data from 17 parents of children with DMD and 6 adult patients. Participants responded to a hypothetical gene therapy vignette with features including non-curative stabilizing benefits to muscle, cardiac and pulmonary function; a treatment-related risk of death; and one-time dosing with time-limited benefit of 8–10 years. We used NVivo 11 to code responses and conduct thematic analyses.

All participants placed high value on benefits to skeletal muscle, cardiac, and pulmonary functioning, with the relative importance of cardiac and pulmonary function increasing with disease progression. More than half tolerated a hypothetical 1% risk of death when balanced against Duchenne progression and limited treatment options. Risk tolerance increased at later stages. Participants perceived a ‘right time’ to initiate gene therapy. Most preferred to wait until a highly-valued function was about to be lost.

Participants demonstrated a complex weighing of potential benefits against harms and the inevitable decline of untreated Duchenne. Disease progression increased risk tolerance as participants perceived fewer treatment options and placed greater value on maintaining remaining function. In the context of a one-time treatment like gene therapy, our finding that preferences about timing of initiation are influenced by disease state suggest the importance of assessing ‘lifetime’ preferences across the full spectrum of disease progression.

Partial Text

Duchenne muscular dystrophy (Duchenne) is a rare neuromuscular disorder with onset in early childhood. The progressive muscle weakness leads to loss of motor function that is further complicated by pulmonary and cardiac complications, leading to death typically in the third decade [1–3]. The distress associated with the Duchenne prognosis, progressive loss of function, and limitations in activities of daily living impact the quality of life of patients [3–5] and their caregivers [6–13].

Consistent with our previous PFDD work [30, 31], study decision making occurs through a consensus-driven process facilitated through an advisory committee comprising a patient representative, a caregiver representative, an expert clinician, and representatives from industry. The committee advised on the development of the instrument, discussed results interpretation and reporting, and participate as authors. Study data is owned by PPMD.

Our findings indicate cautious optimism about gene therapy as a therapeutic option for Duchenne. Our parent and adult participants placed high value on what they perceived as meaningful benefits to function and quality of life. The potential benefits were valued somewhat differently based on disease progression. Benefits to muscle function were important to maintaining or improving mobility in younger children, versus maintaining or improving independence and activities of daily living in older children and adults with Duchenne. Similarly, both groups valued improved cardiac and pulmonary function due to associated lifespan and quality of life benefits. Those in older age groups describe higher relative importance of cardiac and pulmonary benefits compared to muscle benefits.