Duchenne muscular dystrophy (DMD) is a rare and devastating disease, causing progressive muscle weakness and early death. As any physician involved in treating DMD would know, a diagnosis of DMD is incredibly painful for both the patient and his or her family.
When it comes to DMD management, there is much we can do; however, there is also much we cannot do. The glass, being half-full, is naturally also half-empty.
In this article, we will examine the current management options available for DMD patients, and discuss an experimental therapy that could potentially alter the treatment landscape of DMD.
The Present Landscape
Venugopal and Pavlakis wrote a paper summarizing the current state of play of DMD management. On this topic, they do not mince words: “No medical cure exists for this congenital dystrophy, and the disease has a poor prognosis. Treatment is centered on glucocorticoid therapy, prevention of contractures, and medical care of cardiomyopathy and respiratory compromise.”
The purpose of glucocorticoid therapy is to decrease the rates of myotube apoptosis and myofiber necrosis. The most frequently used glucocorticoid is prednisone. Glucocorticoid therapy has been shown to improve pulmonary function, delay the progression of cardiomyopathy, and improve overall mortality.
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With regards to cardiomyopathy, angiotensin-converting enzyme (ACE) inhibitors or beta-blockers should be prescribed to delay the onset of heart failure. Close surveillance of cardiology health is highly recommended. If overt heart failure is detected, digoxins and diuretics should be prescribed.
In addition to the close surveillance of cardiomyopathy, pulmonary function surveillance should also be carried out. This should happen ideally twice a year. Dual-energy x-ray absorptiometry (DEXA) scanning should also be carried out, ideally yearly, to monitor bone health.
“Physiotherapy to prevent contractures is the mainstay of orthopedic interventions,” Venugopal and Pavlakis wrote. In addition, surgery may be needed to correct scoliosis or release contractures in advanced disease.
Nutrition and exercise play an important role in DMD management. DMD patients are at risk of malnutrition and obesity. Supplements containing calcium and vitamin D should be prescribed to prevent the development of osteoporosis secondary to chronic steroid usage. Gentle exercise is highly recommended to prevent disuse atrophy, with care to avoid overexertion.
A Longer-Term Solution?
All the therapies described in the previous section cannot be labeled as curative by any stretch of the imagination; they merely improve quality of life and delay the inevitable. Hence, researchers are looking to find a new approach to treating DMD, with the hopes of more permanent results.
Sarepta Therapeutics recently announced that its investigational gene transfer therapy, SRP-9001, demonstrated sustained functional improvement in studies of patients with DMD.
How does SRP-9001 work? The company explained that it is “intended to deliver its micro-dystrophin-encoding gene to muscle tissue for the targeted production of the micro-dystrophin protein.”
“With 77 patients treated to date, the multi-study development program for SRP-9001 represents the most comprehensive and long-term dataset for a Duchenne muscular dystrophy gene therapy in existence,” said Doug Ingram, the president and CEO of Sarepta.
“The totality of evidence shows that SRP-9001 is a significantly differentiated gene therapy product candidate with one-time dosing and a stable tolerability profile, resulting in robust expression and evidence of sustained functional benefits across our various studies.”
In one study, DMD patients who received SRP-9001 performed better on the North Star Ambulatory Assessment (NSAA) or showed stabilization when a decline would typically be expected. (The NSAA is a rating scale used to measure functional motor abilities in children with DMD who are ambulant). Functional improvements, as soon as 6 months following treatment, were also noted. These findings “place SRP-9001 alone among potential therapies,” according to Ingram.
Working Toward a Cure
Currently, DMD management consists largely of delaying the onset of severe disease. The management options laid out by Venugopal and Pavlakis are the standard treatment protocol for DMD around the world.
In addition, many DMD treatment centers offer counseling or psychological services to patients and their families. The disease burden of DMD is profound, and the care we provide must reflect this as well.
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However, medical researchers are not satisfied with just delaying the onset of severe disease by a few more years. Increasingly, they are working hard to figure out a way toward curative treatment, ie, the complete elimination of this disease. Sarepta’s effort to develop a therapy that increases dystrophin production in muscle tissue is a step in this direction.
What does the future hold for DMD treatment? Certainly, a switch in treatment strategy from palliative to curative care is on the table. We can only wait with bated breath to see what new information clinical research will yield in the years ahead.
Venugopal V, Pavlakis S. Duchenne Muscular Dystrophy. In: StatPearls. StatPearls Publishing; July 14, 2021. Accessed November 28, 2021.
Sarepta Therapeutics’ SRP-9001 shows sustained functional improvements in multiple studies of patients with Duchenne. News release. Sarepta Therapeutics; November 10, 2021.