The impact of orphan drug policies in treating rare diseases.

This paper is based on Shalini Weerasooriya's Masters dissertation in Public Health at the University of Sheffield. A literature review was conducted to understand the role that orphan drug policies have played in the development of new treatments for rare diseases. The impacts of the policies were categorised as 'tangible' or 'intangible' and further synthesis identified 10 main themes such as incentives for investment, criteria for eligibility and assessment of drug applications and further guidance to industry during the drug development cycle. The review concludes that whilst policies have contributed positively towards improving the research and development of orphan drugs it has not exhausted its uses and must now shift its focus to facilitating greater accessibility and affordability of the treatments and that stakeholders are essential to the success of this process. Implications for practice are identified, for example the need to further update and refine the policy with changing demographics and advancing technologies and, in particular, greater collaboration and involvement through, for example, evidence based training programmes is recommended. It is concluded that focus must shift to address the gap between having available drugs and being able to access and afford them. F.J.

Erythropoietin protects cardiomyocytes from cell death during hypoxia/reperfusion injury through activation of survival signaling pathways.

Hypoxia/Reoxygenation (H/R) cardiac injury is of great importance in understanding Myocardial Infarctions, which affect a major part of the working population causing debilitating side effects and often-premature mortality. H/R injury primarily consists of apoptotic and necrotic death of cardiomyocytes due to a compromise in the integrity of the mitochondrial membrane. Major factors associated in the deregulation of the membrane include fluctuating reactive oxygen species (ROS), deregulation of mitochondrial permeability transport pore (MPTP), uncontrolled calcium (Ca2+) fluxes, and abnormal caspase-3 activity. Erythropoietin (EPO) is strongly inferred to be cardioprotective and acts by inhibiting the above-mentioned processes. Surprisingly, the underlying mechanism of EPO's action and H/R injury is yet to be fully investigated and elucidated. This study examined whether EPO maintains Ca2+ homeostasis and the mitochondrial membrane potential (ΔΨm) in cardiomyocytes when subjected to H/R injury and further explored the underlying mechanisms involved. H9C2 cells were exposed to different concentrations of EPO post-H/R, and 20 U/ml EPO was found to significantly increase cell viability by inhibiting the intracellular production of ROS and caspase-3 activity. The protective effect of EPO was abolished when H/R-induced H9C2 cells were treated with Wortmannin, an inhibitor of Akt, suggesting the mechanism of action through the activation Akt, a major survival pathway.