Adults Living with DMD, Parents and Patients, Voice ‘Cautious Optimism’ for Gene Therapy in Interviews

Most parents of children with Duchenne muscular dystrophy and adults with this disease — who took part in an interview study arranged and owned by Parent Project Muscular Dystrophy (PPMD) — expressed “cautious optimism” about gene therapy as a potential DMD treatment, weighing potential benefits against risks and disease progression.

Both groups would tolerate more risk at more advanced stages of the disease, especially in face of the limited treatment options and greater disability accumulation.

And most thought a “right time” existed for a gene therapy’s use, largely placing that optimal time at shortly before a “valued function” is lost.

The study, “Gene therapy as a potential therapeutic option for Duchenne muscular dystrophy: A qualitative preference study of patients and parents,” was published in the journal PLOS ONE.

Several different gene therapies are being investigated to treat muscular dystrophy, and possibly offer the chance of a cure. Gene therapy approaches currently in research for DMD include exon skipping, CRISPR/Cas9, stop codon readthrough and AAV-mediated therapies. 

PPMD, in collaboration with RTI International and an advisory committee, developed this study to explore parents’ and patients’ preferences, understanding, and interest regarding gene therapy as an option for treating DMD. PPMD led participant recruitment, and interviews were conducted by RTI, a nonprofit research institute.

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In total, 17 parents of 20 DMD children (ages 5–32) and six adult patients (ages 21–26) were interviewed. Nine of the 20 children had lost the ability to walk independently; all six adults were fully dependent on wheelchairs.

Participants responded to a hypothetical gene therapy “vignette,” or example, whose benefits include non-curative but stabilizing improvements in muscle, heart and pulmonary function; a treatment-related 1% risk of death; and one-time dosing with effectiveness lasting 8 to 10 years.

Most were cautiously optimistic about such a therapy, although many had ” mixed attitudes about how realistic gene therapy seems to them,” the study noted. A number expressed concern about whether gene therapy could work for patients with a range of gene mutations, and its likely benefits.

Nevertheless, all strongly valued potential gains in skeletal muscle, and in heart and lung function. Preserving skeletal muscle was mostly a priority among parents whose children were younger and earlier in their disease course, while parents of older children put greatest value on heart and lung function, followed by skeletal muscle as a means of maintaining quality of life and independence.

“But the heart and lungs are the weak spot, and it’s not the disease that kills these boys. It’s the risk of pneumonia and the common cold and the simple things that take them from us so early. So yes. Heart and lung function is A one, number one priority,” one parent told interviewers.

Patients put greatest emphasis on a gene therapy that would stop decline, allowing them to care for themselves and be independent in daily life. Younger adults here favored treatments possibly offering gains in functional abilities and retaining muscle strength; older ones emphasized stabilization.

“I’m right on the verge of possibly losing ability to use the bathroom myself or eat myself or drink myself, and maintaining ability to do that would be really, really huge for me,” a patient said.

Treatment risk was set as a scenario in which 1 in every 100 people given this therapy die soon after infusion due to a massive immune response. Slightly more than half of the parents (nine out of 17) were willing to trade anticipated benefits for that 1% risk of death, even as a one-time-only therapy with benefits reaching out to a maximum of 10 years.

“Eight to ten years for anybody is more than what they have right now,” one parent said.

“If you get eight to ten years to stop the progression when you’re young, that’s enormous because a lot of the progression [occurs] when the skeletal muscle turns to scar tissue, like it can’t come back,” said a patient.

Added another: “I guess you could use it if there’s anything like major going on … eight years is a ton. There could be more stuff available by that time then.”

Type of administration did not interest or concern participants greatly, nor did a one-time use among most interviewed. Several parents voiced concern about a one-time therapy that didn’t work as planned after a first use, and how their child’s treatment options would then be affected.

Half of the parents and most adult patients spoke favorably about participating in gene therapy clinical trials, given the few current treatment options. A concern for most parents, especially those with younger children, was their child’s ineligibility for future trials.

Most patients, in contrast, were “not particularly concerned” about losing the possibility of taking part in future studies, “due to their perception that there were few or no trial options available to them,” the study said. Most DMD trials, it also noted, are designed for younger children.

A important study finding, it authors stressed, was that participants thought there was a “right time” to initiate gene therapy. Most preferred to wait before until a highly “valued function” was about to be lost. For instance, most parents favored waiting until their child’s motor abilities started to decline or at an older age; only two parents favored giving it to a toddler.

The study concluded by noting that its findings suggested gene therapies carried “specific educational needs” relating to their potential risks, type and duration of benefits, and other limitations because of many uncertainties about this potential treatment.

“Our findings support the importance of measuring preferences and risk tolerance at different stages of disease. Given the current science of gene therapy, uncertainty is inherent in any descriptions of benefits and harms, and our participants referenced the impact of uncertainty on their attitudes,” its researchers wrote.

“Future research should further address the role of uncertainty in the appraisals and preferences of patients and parents, and continue to assess preferences as emerging clinical trial data cause uncertainties to diminish.”

PPMD, the study also noted, is developing “an educational initiative to meet the needs anticipated by and identified in this study.”

This work was funded by PPMD, which received support from Solid Biosciences and Pfizer.