The Promise Of Precision Medicine

"Large-scale genome sequencing and correlating the DNA signatures with specific disease or drug sensitivity will allow clinicians to specify personalised treatment," says Rakesh K Mishra, Director, Centre for Cellular and Molecular Biology.

Illustration by Raj Verma Illustration by Raj Verma

Our body is a complex machine with hundreds of parts, and its maintenance is critically linked to the information stored in our DNA sequences. It not only determines our body's response to medicines but also how our body reacts to the environment around us. Understanding the genetic framework is, therefore, essential if we have to treat any medical condition.

Getting a complete genome sequence done at an affordable cost and within a very short span (say, within a few days) is the way ahead, and we are getting there. Empowering clinicians with these details will open the doors to targeted therapy and personalised medicine - one that is guided by the linkages of DNA signatures with specific diseases or to responses of the human body to certain drugs.

While Genome-sequencing of a large number of individuals allows scientists to correlate the normal and the defective cellular functions in respective cells types to specific DNA sequences. Due to the uniqueness of one's genome sequence, it is possible to assign genome signatures to the variations seen in susceptibility to infectious agents, environmental factors/stress, response to various drugs and so on.

Some individuals may break down or metabolise a drug faster than others so that it is active for a shorter time in their bodies. Such people, with faster metabolic rates, will need a higher dose of the drug compared to people with slower metabolic rates for the same medicine. It is possible to link this differential metabolic rate to a specific DNA sequence in the genome. The genome codes for proteins that function as enzymes to metabolise drugs.

One could imagine that an enzyme that metabolises this drug may be more active in one individual due to a slight change in the sequence of the enzyme. Similarly, a slight change in the protein surface (which is the target for a particular drug), due to variation in the corresponding gene, may render the drug ineffective in such individuals. In brief, sequencing genomes of a large number of individuals and correlating the DNA signatures with a specific disease phenotype or drug response will allow clinicians to specify personalised treatment, including specific drug type, dose and duration, to treat a disease. This sort of personalised and precision medicine is not very far.

Precision medicine takes a whole new meaning when cells taken from an individual can be converted to specific tissue type or into a laboratory-grown tumour, say in case of cancer. This can be used to screen available options of medicines and decide which one is best-suited with least undesired toxicity.

It has also been demonstrated that tumour cells from a patient can be marked and transferred to convenient alternative animal models like the zebrafish. There, the tumour grows in a few days and is ready for such testing. The patient can then be given the correct type of drug and a suitable dose. Research in such personalised medicine approaches has made remarkable progress and should be available to patients at an affordable cost in the near future.

As of now, new drug developments are expensive and time-consuming, mainly due to different types of testing and trials required, initially involving animals and later on, human volunteers. But this can all change with testing made possible under laboratory conditions.

New drugs can be tested directly on appropriate organoids, and the new procedure will drastically cut the cost and time of testing by avoiding or at least significantly reducing much of the testing and trials done with animal models and human volunteers. Drugs developed in this way could also be optimised for a particular ethnic group or even an individual, based on the respective genome sequence information.

There are diseases for which no drug is available. Treating such patients requires replacing body cells or part of the organ. Cell-based therapies are now within sight as cells can be grown in large numbers after being modified and optimised using genome-editing technologies. This approach could potentially treat many medical conditions, including genetic/inherited diseases, for which there is no cure at present.

Cell-based therapy is available in rich countries, but it is only a matter of time when the cost will not be as prohibitive as it is now and will be available in countries like India. According to some estimates, the current market size of cell-based therapy is around $10 billion globally and likely to double in two-three years. It also signals the scope for new biotech developments in the healthcare sector.

The ability to pick cells from patients, change their properties using genome-editing technologies, add new features/pathways and then use them as a source to produce a large quantity of a desired bioactive product is yet another approach of custom-made and optimised precision medicine. A key advantage of using cell-based or bioactive therapy is that it is likely to have minimal toxic effects compared to small-molecule pharmaceuticals and, therefore, may replace those to a large extent.

The specificity and ease of changing their properties using molecular and cell biology approaches make bioactives, including antibody-based immune therapy, one of the major treatment options in future with more and more personalisation and precision options.

While technology is offering unprecedented alternatives, a lot remains to be covered before such alternatives become accessible and affordable. One of the major tasks is the creation of strong regulatory guidelines that facilitate new treatment options and also protect patients' interests. There are new business opportunities in the healthcare industry which will emerge from such developments.

Policies and regulations will be needed to safeguard intellectual property while protecting individuals from possible exploitation or discrimination. Another challenge is to effectively generate and correlate genome sequences to diseases and drug sensitivity in individuals hailing from different ethnic origins. The question is: How long will it take before these options become available and affordable? The answer: Maybe less than 10 years!