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Table 1 Summary of vascular targeted therapies for Duchenne muscular dystrophy

From: Vascular-targeted therapies for Duchenne muscular dystrophy

Treatment Outcome Physiologic effects (mdx mice) Physiologic effects (DMD patients) Potential pharmaceuticals Future directions
Angiotensin-converting enzyme (ACE) Inhibitors Improved vasorelaxation capacity Improved myocardial function (prior to onset of cardiomyopathy)[31]. Prevented angiotensin II dependent stimulation of pro-oxidant and pro-inflammatory pathways[51]. Delayed onset and progression of LV dysfunction and lower mortality rates in 9.5 to 13 year olds with normal cardiac functioning[32, 33]. Myocardial functional improvements in some cases with established cardiomyopathy[34, 36]. Given in combination with BBs, patients with established cardiomyopathy saw positive effect on long term survival[35]. FDA approved ACEIs to treat heart failure and hypertension include: benazepril (Lotensin™), captopril (Capoten™), enalapril (Vasotec™), fosinopril (Monopril™), lisinopril (Prinivil™, Zestril™) moexipril (Univasc™), perindopril (Aceon™), quinapril (Accupril™), ramipril (Altace™), and trandolapril (Mavik™). Decide effective pharmaceutical agent and use clinical trial to assess potential prophylactic benefit and/or ability to attenuate functional ischemia.
Phosphodiesterase 5 (PDE5) Inhibitors Improved Vasorelaxation Capacity Decreased myofiber damage after myofiber injury[24]. Improved muscle histology with treatment started at conception[24]. Reduced cardiomyopathy remodeling signals[54, 55]. Reversed myocardial dysfunction in models with established cardiomyopathy[56]. N/Da PDE5 inhibitors that are FDA approved for treating erectile dysfunction or hypertension include: tadalafil (Cialis™ or Adcirca™), sildenafil (Viagra™ or Revatio™), and vardenafil (Levitra™ or STAXYN™). Complete the in-progress phase 1 clinical trial (NCT01580501) assessing the ability of tadalafil and sildenafil to attenuate functional ischemia in boys with DMD.
Vascular Endothelial Growth Factor (VEGF) Administration Increased Vascular Density Increased forelimb strength and reduced necrotic fiber area[67]. Pro-myogenic effects, including increased regenerating fiber area and number of activated satellite cells in skeletal muscles[67]. N/Da Engineered myoblasts expressing VEGFb, VEGF protein systemic injectionsb, adeno-associated viral (AAV) VEGF vectorsb Determine best strategy and dosing schedule for delivery, acquire more safety data, and agree on values that constitute therapeutic increases in vascular density. Assess potential prophylactic benefit and/or ability to attenuate functional ischemia in mdx mice.
  1. aN/D, not determined. bThese are not Food and Drug Administration (FDA) approved and are undergoing pre-clinical investigation in mdx models.