Drug repositioning in pulmonary arterial hypertension: challenges and opportunities.

Despite many advances in medical therapy for pulmonary arterial hypertension (PAH) over the past 20 years, long-term survival is still poor. Novel therapies which target the underlying pathology of PAH and which could be added to current vasodilatory therapies to halt disease progression and potentially reverse pulmonary vascular remodeling are highly sought after. Given the high attrition rates, substantial costs, and slow pace of new drug development, repositioning of "old" drugs is increasingly becoming an attractive path to identify novel treatment options, especially for a rare disease such as PAH. We here summarize the limitations of current PAH therapy, the general concept of repurposing and repositioning, success stories of approved repositioned drugs in PAH as well as novel repositioned drugs that show promise in preclinical models of pulmonary hypertension (PH) and are currently tested in clinical trials. We furthermore discuss various data-driven as well as experimental approaches currently used to identify repurposed drug candidates and review challenges for the "repositioning community" with regards to funding and patent and regulatory considerations, and to illustrate opportunities for collaborative solutions for drug repositioning relevant to PAH.

The trials and tribulations of repurposing metformin and other generic drugs for tuberculosis.

There are a number of generic drugs that might be useful in treating tuberculosis, but will they ever get to the patients who need them? They might, but not without a lot of help. There are intellectual property issues, endpoint issues, cost of research issues, economic incentive issues, preclinical validation issues, "who is in charge" issues and many more. It is clear that repurposed generic drugs have the potential to make a safe, effective, quick and affordable impact on a global disease of poverty such as tuberculosis. But without the economic incentives that are usually in place for drug development, can we muster the scientific, economic and governmental support to bring them to the patients?

Creating New Economic Incentives for Repurposing Generic Drugs for Unsolved Diseases Using Social Finance.

Repurposing research improves patient lives by taking drugs approved for one disease and clinically testing them to create a treatment for a different disease. Repurposing drugs that are generic, inexpensive, and widely available and that can be taken in their current dosage and formulation in the new indication provide a quick, affordable, and effective way to create "new" treatments. However, generic drug repurposing often provides no profit potential, and so there is no economic incentive for industry to pursue this, and philanthropy and government funds are often insufficient. One way to create new economic incentive for the repurposing of generic drugs is through social finance. This perspective describes how social finance can create a new economic incentive by using a social impact bond, or similar financial structure, to repay for-profit investors who fund the repurposing research from the proceeds of healthcare cost reductions generated when these affordable, effective, and widely available repurposed therapies improve healthcare outcomes.

Meeting the challenges of an emerging pathogen: the Henry Schueler 41&9 Foundation International Forum on Mucormycosis.

Invasive mucormycosis comprises a group of uncommon but emerging life-threatening pulmonary, sinal, rhinocerebral, and disseminated infections, which cause debilitating morbidity and severe mortality in our most vulnerable pediatric and adult immunocompromised patients. While important advances are being achieved in understanding the epidemiology, molecular taxonomy, pathogenesis, pharmacology, host defenses, and microbiology of these infections, there are critical needs for improving these approaches for diagnosis, treatment, and prevention. This supplement is dedicated to the memory and courage of Hank Schueler, who fought valiantly against this infection. It provides a comprehensive resource for current approaches to management of this infection and also reviews the key advances against invasive mucormycosis.