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 (Lotensinâ„¢), captopril (Capotenâ„¢), enalapril (Vasotecâ„¢), fosinopril (Monoprilâ„¢), lisinopril (Prinivilâ„¢, Zestrilâ„¢) moexipril (Univascâ„¢), perindopril (Aceonâ„¢), quinapril (Accuprilâ„¢), ramipril (Altaceâ„¢), and trandolapril (Mavikâ„¢). | 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 (Cialisâ„¢ or Adcircaâ„¢), sildenafil (Viagraâ„¢ or Revatioâ„¢), and vardenafil (Levitraâ„¢ or STAXYNâ„¢). | 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. |