application and indication. The additional advantage of the strategy is that these

drugs may be repurposed during any stage of their evolution right from their

development stage or discovery.

A drug many a times is approved in spite of scientifically tested and known side

effects in the desire of better therapeutic potential for the treatment of other diseases.

Sildenafil is a classic example. It was originally tested and developed for treating

patients

having

hypertension

and

angina

pectoris,

but

because

of

its

phosphodiesterase-5 inhibitory action, it has currently captured a huge market for

effectively managing erectile dysfunction in patients (Boolell et al. 1996). Another

example is itraconazole which was initially approved as an antifungal agent but then

was found to have an excellent effect towards anti-angiogenesis property (Chong

et al. 2007; Rudin et al. 2013). Saracatinib is yet another example. This molecule

developed by AstraZeneca as an anticancer agent failed initially but exhibited

substantial reversal and good effects of symptoms in Alzheimer’s disease

(AD) when tested in mice model (Nygaard et al. 2015).

One of the recent examples is remdesivir, which was initially developed by

Gilead Sciences in 2009 for hepatitis C. It did not work for hepatitis C and was

repurposed for Ebola virus and other viruses including coronavirus. In 2020,

remdesivir is approved for use in the treatment of Covid-19. In Covid-19, the active

metabolite of remdesivir interferes with the viral RNA-dependent RNA polymerase

(RdRp),

which

evades

proofreading

by

viral

exoribonuclease

(ExoN)

in

nanostructured protein (nsp 14), ultimately causing a decrease in viral RNA produc-

tion (Yin et al. 2020). There are some relevant examples of existing repurposed

drugs in the market described below (Table 9.1) along with the intended and new

indication.

9.5.2

Development of Patient-Driven Diagnostics with Reverse

Translational Approach

With the change in the technology and supporting techniques such as machine

learning and the use of automated machines, the role of patients in health research

is changing continuously and dramatically with positive results. Earlier the patients

under testing were considered as study ‘subjects’; however, today patients signifi-

cantly play an important and critical role while initiating and collecting the data in

every stage of the ongoing research activities. This is impactful when such involve-

ment occurs, which further ensures that study results are more practical and useful to

the researchers and patients and to others involved in making important healthcare

decisions and commercialisation. It is imperative to note that active involvement of

patients eventually bring issues with possible solutions that matter to them including

the quality of life and the effectiveness of healthcare options. Furthermore, these

steps are working alongside scientists as partners and are being tested and evaluated

in designing and conducting research protocols and policy and are key measures for

the successful dissemination of knowledge and implementation of the outcome and

interpretation for further use. Considering patients’ perspectives, the researchers will

9

Biomarker-Based Drug Discovery with Reverse Translational Approach

135