**5. Future perspectives of drug repurposing in orphan disease therapeutics**

As orphan disease affects a small percentage of the population, research and pharma companies face great challenge and burden in developing drugs for its management because of small market potential. Patients fail to get proper care, diagnosis and treatment. Even if the treatment is available, it is relatively expensive. Thus, drug repurposing can be of great help in orphan disease therapeutics. It saves both' the time and money involved in the drug development process. In October 2010, "Dr Ruxandra Draghia-Akli, the Directorate-General for Research and Innovation (DG RTD) of the European Commission (EC) and Dr Francis Collins, US National Institutes of Health (NIH)" at Reykjavík (Iceland), launched the International Rare Diseases Research Consortium (IRDiRC) to look after the drug and research development in orphan/rare diseases [34]. This consortium unites both government and private research funding societies to advance the drug development for orphan diseases at global level including task forces and drug repurposing in orphan disease therapeutics.

The research in rare diseases has already changed the global approach because earlier researchers were not much interested in repurposing the existing drug but some global breakthrough has really changed the minds of pharma companies and examples are alglucerase that was obtained from human placental tissue and was widely used for Type I Gaucher disease as a "first enzyme replacement therapy" and, it was also approved by FDA in 1991. However, it was withdrawn from the market due to adverse effect and already available drugs in the market which are prepared from recombinant DNA technology which are safe to use [35]. Fomivirsen which is an antisense oligonucleotide and was approved by FDA for

Cytomegalovirus in 1998 but it has been withdrawn from the market due to the development of highly active antiretroviral therapy (HAART) but this was the "first antisense oligonucleotide therapy" [35]. Imatinib was approved by FDA in 2001 for Philadelphia chromosome-positive chronic myelogenous leukemia (CML) as "first targeted cancer therapy" [35]. Alipogene tiparvovec was the "first targeted gene therapy" to be approved in Europe in 2012 for reversing lipoprotein lipase deficiency (LPLD) in patients with pancreatitis [35]. Strimvelis was the "First ex-vivo gene therapy" approved for patients with Severe Combined Immunodeficiency due to Adenosine Deaminase deficiency (ADA-SCID) [35]. USFDA has approved Holoclar as orphan drug for the treatment of limbal stem cell deficiency (LSCD). Currently, this drug is in Phase IV trial and completing in mid of the year 2020 [36].

To overcome R&D-associated financial challenges and clinical trials-related failures of novel drugs, at present scenario, pharmaceutical companies are much more interested in switching to "drug repurposing" or "drug repositioning" drug development by adopting various computational approaches rather than going for de novo drug discovery, which is relatively expensive, risky and time consuming [37]. According to Southall et al. [35], the global market for drug repositioning will possibly be hiked to over \$31 billion by 2020, up from about \$24 billion in 2015, thus representing large commercial possibility [35].
