Cell-Based Gene Therapy in Pulmonary Arterial Hypertension

> “As you set out for Ithaka, hope the voyage is a long one, full of adventure, full of discovery.> > Keep Ithaka always in your mind. Arriving there is what you are destined for…> > But do not hurry the journey at all. Better if it lasts for years, so you are old by the time you reach the island,> > wealthy with all you have gained on the way, not expecting Ithaka to make you rich…> > And if you find her poor, Ithaka won’t have fooled you.> > Wise as you will have become, so full of experience, you will have understood by then> > what these Ithakas mean.”> > from Ithaka, by C.P. Cavafy1Pulmonary arterial hypertension (PAH) is a relatively rare but fatal disease. However, with the advances in diagnostic tools and our organized approach (most tertiary-care centers now have PAH programs), we now know that PAH is more common than we thought even 15 years ago, although precise estimates of global incidence and prevalence are lacking. PAH is projected to become a 5-billion-dollar industry by the end of this decade,2 as most of the approved 3 classes of therapies (phosphodiesterase type 5 inhibitors/cGMP modulators, endothelin antagonists, and prostacyclin analogues) are expensive. The vast majority of clinical trials with these drugs have been short (≤6 months) and have not included mortality as a primary end point, and there is no prospective evidence that these therapies can prolong life or reverse the progression of the disease. On the other hand, it seems that they can improve symptoms or decrease hospitalizations.3 The ultimate treatment remains lung transplantation, and there are currently no therapies to treat the major complication of the disease, that is, right ventricular failure. Yet, there are myriads of promising therapies at the preclinical stage.3 Like in many other …