Experts in the diagnosis and treatment of Duchenne muscular dystrophy share their perspectives on the complex care of this patient population in the NeurologyLive® Insights series “Management of Duchenne Muscular Dystrophy.”
Crystal Proud, MD
The treatment landscape for Duchenne muscular dystrophy (DMD) continues to be quite lively, as the FDA recently approved viltolarsen (Viltepso; NS Pharma) for patients with DMD amenable to exon 53 skipping, marking only the second FDA-approved therapy for the DMD gene mutation that affects 8% to 10% of patients.1 Additionally, the agency recently granted orphan drug designation to Vita Therapeutics’ VTA-110, an allogeneic induced pluripotent stem cell–based therapy, as it advances to human trials2; and Catabasis’ oral small molecule NF-kB inhibitor, edasalonexent, was deemed well tolerated in the phase 2 MoveDMD trial.3
Although the increased activity in the DMD drug pipeline could mean more effective disease-modifying treatments in the near future, the current approach to treatment relies on large teams of multidisciplinary physicians and other health care professionals who offer comprehensive, symptomatic disease management.
Challenges of the multisystem impact of DMD require a collaborative and mixed-specialty approach in its management. To learn more about the care that is provided by the team, several experts in DMD recently came together to share their thoughts in the NeurologyLive® Insights series “Management of Duchenne Muscular Dystrophy.”
Mechanistically, DMD disrupts the production of dystrophin, the lack of which impacts muscle function throughout the body. This functional deficit is at the root of the requirement for patients’ multidisciplinary management.
“We see weakness in the arms and legs, weakness of the respiratory muscles, and we see an impact, as well, to the cardiac muscles,” said Crystal Proud, MD, pediatric neuromuscular neurologist at Children’s Hospital of The King’s Daughters in Norfolk, Virginia. “In addition, we can’t forget about the muscles that allow us to do things like chew and swallow, and those that impact bowel and bladder habits. So, it really requires a comprehensive team to be able to care for the patients with DMD.”
Proud noted that her institution’s DMD team includes herself as well as a physiatrist, who helps provide accommodations to patients that can improve their overall quality of life and their ability to participate in activities of daily living; these apparatuses include wheelchairs, transfer boards, back chairs, and braces.
Additionally, depending on the patient, the team can include physical and occupational therapists, a pulmonologist, a cardiologist, an orthopedist, an endocrinologist, an educational liaison, a dietician, and social workers. Occasionally, the team expands to include surgeons as well.
A patient’s physical therapy regimen often includes routine standardized testing to track progression, which helps detect any functional decline, Proud explained. Progression, in turn, can trigger changes in supportive care recommendations. The test results also allow the occupational therapist to provide guidance for patient accommodations at home or school.
"When we start to see that the respiratory muscles are impacted, [the pulmonologist] intervenes with things such as CoughAssist devices, and sometimes we utilize a vest to help loosen secretion. Ultimately, we end up utilizing devices to help support respiration, like a bilevel support device or bypass device,” Proud said. The impact of DMD on the heart requires routine assessment via echocardiograms and, potentially, cardiac MRIs, which the cardiologist uses to assess and optimize heart function.
Team structure varies by institution but generally includes the same primary stakeholders, said Amy D. Harper, MD, associate professor and medical director of the Muscular Dystrophy Association Care Center at Children’s Hospital of Richmond at Virginia Commonwealth University. She explained that those specialists spend the majority of their time working together in the clinic to support patients and decide on each one’s next best steps.
"Then we have additional supports. A speech therapist may help a child with eating, making sure there is no difficulty with swallowing. They’ll work closely with the nutritionist to monitor weight and growth,” Harper said. The standard use of steroids in children with DMD tends to result in stunted growth and weight gain that, when left unattended, can cause such other problems as adrenal insufficiency or delayed puberty. An endocrinologist may help monitor those parameters.
Many of the effects of DMD and its treatment require additional accommodations and services outside of the clinic. Social workers often assist with such aspects as 504 plans or individualized education plans.
"There can be additional ancillary services outside, including parental or family support organizations,” Harper explained. “Identifying an ophthalmologist and primary care doctor who are comfortable with multiple specialists is also important,” she said. “It takes a village. My nurse coordinator describes our weekly clinics as a [being like a] wedding, [needing to be pulled] all together, but it’s the best care for the patients with DMD.”
The village-type approach Harper described begins at diagnosis. Because DMD is a genetic condition, getting a quick and precise diagnosis of the patient is important not only to provide the earliest possible access to care, but to prevent unnecessary testing. A blood test for creatine phosphokinase, which tends to be elevated in DMD, can point physicians in the direction of muscular dystrophy.
Genetic confirmation helps to delineate DMD from other muscular dystrophies that present similarly, such as limb-girdle muscular dystrophy and congenital muscular dystrophy. Genetic testing has sensitivity of about 95%, or even more, in confirming diagnoses. Emma Ciafaloni, MD, professor of neurology and pediatrics, codirector of the MDA Neuromuscular Clinic, and director of the Neuromuscular Medicine Fellowship Program at the University of Rochester Medical Center in New York, noted that the responsible steps after a DMD diagnosis are genetic tests and counseling for the patient and their family.
"Genetic counseling for the family is important [because it allows us] to educate them about the possibility of having other children affected by the disease in subsequent pregnancies,” Ciafaloni said. “It’s also extremely important because although the standard-of-care treatments and corticosteroids are good for all patients with DMD, we now have other, more genetic-specific treatments that are really targeted to specific subgroups of patients with Duchenne. Those are applicable only to a portion of patients, depending on their precise genetic mutations”
Ciafaloni emphasized the seriousness of a DMD diagnosis. The disease is “universally progressive” and has an all-encompassing impact on patients, many of whom become wheelchair bound by their late teens. “It’s very tragic for a family to learn about this diagnosis and to really cope with the long journey of living with this disease,” she said.
Beyond the obvious physical challenges, patients and families have emotional challenges after diagnosis that need attention. A team’s social worker, Harper noted, can help provide an understanding of psychosocial supports and help ensure that patients are ready for the transition processes they will undergo. It’s particularly crucial to inform patients and their families about advocacy organizations that allow them to connect with and meet others directly and indirectly affected by the disease.
"They can really become empowered and educated, and they learn that living with this disease is, in fact, very much possible,” said Harper. “Then, they don’t feel [so] isolated and alone with this serious diagnosis.”
Patients with DMD often need several supportive treatments in addition to steroids, but each additional treatment adds another layer to the complexity of management. Aside from the necessary growth and weight monitoring that accompany steroid administration, this standard-of-care treatment comes with an increased risk of infection. As such, patients must be vigilant about receiving, say, yearly vaccinations for influenza and pneumonia. In addition, heart-centric therapies may be prescribed based on cardiologist recommendations.
In addition to bringing in CoughAssist when necessary, respiratory therapists teach techniques like breath stacking, and sleep specialists may be asked for their expert opinions on sleep study results. If hypoventilation is detected, a bilevel positive airway pressure machine, or BiPAP, may be prescribed.
"[Also,] from an orthopedic standpoint, there can be progression of scoliosis as the child becomes weaker over time,” Harper explained. “It’s important to treat scoliosis so you can maximize the pulmonary status. Orthopedic interventions offer a lot of benefits.”
Early initiation of physical therapy, too, can help establish a good routine with stretching and the use of night splints, Harper noted. “Starting those routines early makes it easier to prevent long-term contractures at the ankles, which will result in prolonged ambulation as well,” Harper said. Establishing these relationships and familiarity with physical and occupational therapies can make for a smoother transition once adaptive devices and wheelchairs are needed.