A Rational Approach to Drug Repositioning in β-thalassemia: Induction of Fetal Hemoglobin by Established Drugs

Abstract

Drug repositioning and the relevance of orphan drug designation for β-thalassemia is reviewed. Drug repositioning and similar terms ('drug repurposing', 'drug reprofiling', 'drug redirecting', ‘drug rescue’, ‘drug re-tasking’ and/or 'drug rediscovery') have gained great attention, especially in the field or rare diseases (RDs), and represent relevant novel drug development strategies to be considered together with the “off-label” use of pharmaceutical products under clinical trial regimen. The most significant advantage of drug repositioning over traditional drug development is that the repositioned drug has already passed a significant number of short- and long-term toxicity tests, as well as it has already undergone pharmacokinetic and pharmacodynamic (PK/PD) studies. The established safety of repositioned drugs is known to significantly reduce the probability of project failure. Furthermore, development of repurposed drugs can shorten much of the time needed to bring a drug to market. Finally, patent filing of repurposed drugs is expected to catch the attention of pharmaceutical industries interested in the development of therapeutic protocols for RDs. Repurposed molecules that could be proposed as potential drugs for β-thalassemia, will be reported, with some of the most solid examples, including sirolimus (rapamycin) that recently has been tested in a pilot clinical trial.

The Long Scientific Journey of Sirolimus (Rapamycin): From the Soil of Easter Island (Rapa Nui) to Applied Research and Clinical Trials on β-Thalassemia and Other Hemoglobinopathies

“…When our group originally explored the possibility of using rapamycin to treat β-thalassemia [ 89 , 90 , 91 ], knowledge of the action of the drug on erythroid cells was still largely incomplete. On the other hand, many experiments were already designed to characterize agents capable of augmenting HbF levels in humans [ 109 ]. Along this line, our group found that many agents, some of them derived from plants, were indeed able to exert such action in vitro.…”

Pharmacogenomics of Drugs Used in β-Thalassemia and Sickle-Cell Disease: From Basic Research to Clinical Applications

“…In consideration of the role of HbF production in β-thalassemia and SCD, efficient HbF inducers were developed for the treatment of β-thalassemia patients characterized by a low production of HbF [55][56][57][58][59]. Despite the high and growing numbers of HbF inducers, clinical trials are ongoing for a limited number of them, as depicted in Table 1 .…”

Reinventing Therapeutic Proteins: Optimizing Investments and Meeting Humanitarian Needs

“…6 Examples of chemical drugs have been repurposed for benign prostatic hyperplasia, angina, sedation, nausea, and insomnia; later, they were repurposed for use in hair loss, erectile dysfunction, and leprosy, respectively. 7 Examples of serendipitous discovery include sildenafil, intended Disclaimer/Publisher's Note: The statements, opinions, and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions, or products referred to in the content.…”