5.3

Genomic Approaches to DR

Human genetics is a broad field of study that, in part, identifies genetic risk factors

that are common amongst complex, rare, or common diseases (Bush and Moore

2012). Disease being a no stranger term denotes harmful deviations from the normal

state of structure or function of an organism. This entails the state of complete

physical, mental, and social well-being. There are generally four main types of

disease: genetic, infectious, deficiency, and physiological diseases. Genetic disease,

in particular, has both hereditary and non-hereditary scenarios. Genetic disease or

more commonly known as genetic disorder is a health condition where there are

abnormalities in the genome of an individual. A genetic disease may manifest in

various forms ranging from a single gene mutation or chromosomal mutation, which

entails multiple genetic mutations, thus affecting many body systems and causing

great damage. Medicines are usually designed to treat genetic diseases via two main

approaches—restore normal levels of genes with a loss-of-function mutation or

inhibit excessive gene expression in those that have a gain-of-function mutation

(Sun et al. 2014).

Apart from the difficulty in accurate diagnosis, a genetic disease often has no

effective treatment or no treatment at all. This is often caused by changes in genes

which are very complex, life-debilitating, and sometimes rarely occurring; albeit, the

latter is not an absolute (FAQs About Rare Diseases 2021). For genetic conditions,

most treatment and management strategies are only in place for alleviating the

symptoms. For example, a bone marrow transplant for sickle cell disease limits the

intake of certain substances that are potentially toxic for individuals with a metabolic

disorder, which otherwise will be normally broken down by digestive enzymes in

healthy individuals.

Although it is not always the case, a genetic disorder can sometimes be described

as “rare” or as an “orphan disease”. It often affects minute portions of individuals

instead of the mass public like the current COVID-19 pandemic. The biggest hurdle

to tackle genetic diseases lies within the complexity and rare occurrence, in which no

effective treatment is available (Dunoyer 2011; Muthyala 2021; Sardana et al. 2011).

To complicate the situation, some genetic changes may increase the risk of health

problems, such as breast cancer BRCA1 and BRCA2 gene mutations. Additionally,

the low availability of clinical trial subjects is a limiting factor for drug development,

drawing interest away from researchers and pharmaceutical industries as the invest-

ment of time and money may not be profitable (Wästfelt et al. 2006). To date, there

are more than 7000 genetically associated orphan diseases, and still, the number is

continuously rising (Xu and Coté 2011).

In response to this perturbing challenge, DR might be the solution to curb life-

threatening and debilitating genetic diseases. With DR, the ever-concerning cost and

time issue for a low demand drug, especially for complex genetically associated

diseases, can be resolved by exploring new avenues from existing or abandoned drug

therapies. To date, DR plays an important role in bridging the gap closer over access

to medicine by broadening the availability of drug treatment for various diseases

within a population. Indeed, there have been a few notable successes for rare/orphan

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Genomic Approaches for Drug Repositioning

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