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The future of medicine

- Delia du Toit

Imagine a world where medicines can be guided to the exact place that they are needed in the body – a world closer than you think.

For centuries, smallpox ravaged humankind. During the 18th Century, 400 000 people died every year in Europe from the viral disease. The earliest evidence of skin lesions resembling those of smallpox was found on the faces of mummies from the Egyptian dynasties as early as 1570 to 1085 BC. Thanks to the development of a vaccine in the late 1800s, smallpox has since been wiped from the face of the earth.

Such is the nature of medical innovation. Once a viable solution to a problem has been found, a disease can become part of the history books. It is not such a big reach, then, to assume that some of today’s biggest medical challenges such as hypertension, various cancers, and even certain forms of paralysis could be more easily treatable in the coming years.

Medicine, health care, infections | Curiosity 16: #Drugs ©

Developments in drug delivery

Professor Yahya Choonara, Chair and Head of Pharmacy and Pharmacology in the Faculty of Health Sciences as well as Principal Researcher and Co-Director of the Wits Advanced Drug Delivery Platform (WADDP), is one of the experts leading the charge in advances in drug delivery. The WADDP, he explains, focuses on three broad areas: advanced drug delivery that delivers medicine to specific sites in the body; nanomedicine, which reduces formulations to a nano scale for better targeting; and tissue engineering and regeneration, which includes such marvels as the 3D bioprinting of human tissue.

“Advanced drug delivery is the science of developing 21st Century therapeutic interventions that ensure drugs can reach their target site of action in the body. This is beneficial because it  improves the absorption and effect of medicines and significantly reduces side-effects. Some examples of targeted drug delivery technologies and nanomedicines include stimuli-responsive biomaterials, self-assembling molecules, ultrafast or extended-release delivery systems, and multilayered tablets that can be taken once but absorbed at different rates, and even the use of magnets to guide drugs to certain parts of the body.”

The focus of current projects at the WADDP is on infectious diseases such as HIV and TB, targeted anti-cancer therapeutics, 3D-bioprinted wound healing systems, bio-inspired tissue engineering, and oral insulin systems.

Thriving tissue regeneration

Merging nanomedicine with tissue engineering is changing the face of regenerative medicine.

One such exciting development from the WADDP is the work of Dr Poornima Ramburrun, a researcher in biomaterial design and tissue regeneration, who designed a biodegradable hydrogel conduit used to repair peripheral nerve injuries.

Currently, treatment for such cases involves taking nerves from another site in the patient’s body, creating two compromised sites. Alternatively, cadaveric donor tissues are used, which are sometimes rejected by the patient's body. This new device offers a better alternative, and a patent has already been granted in South Africa, Europe, the USA, and China.

“Where nerves have been severed due to traumatic injuries such as vehicle accidents, or stab or gunshot wounds, the nerves have limited capacity and need assistance to regrow. This conduit acts as a bridge across that gap and protects growing nerves from the surrounding inflammatory environment, while releasing drugs to help the nerve fibres to regenerate. The device looks similar to the clear ink tube inside a pen, and it is sutured by a surgeon to either side of the damaged nerve,” she explains.

Another very promising project is that of Dr Gillian Mahumane, who has developed a nano-reinforced hydro filled 3D scaffold for neural tissue engineering in the brain. She explains: “Brain tissue has a hard time repairing itself, sometimes causing a loss of function. So, if, for example, a small tumour is surgically removed, leaving a cavity, the brain tries to heal that tissue very quickly to restore the communication network, forming a scar that can block neurons.

“This device mimics healthy tissue to trick the brain into not responding immediately to repairing it, and instead carrying on with its normal daily cleaning and regeneration at the site, as if this was healthy tissue, eventually rebuilding healthy tissue at the injured site. Nerve signals travel across the scaffolding, which is biodegradable so that the body can break it down when its job is done.”

Jumps in genetics

In tandem with these innovations, advances in genetics research make ‘personalised’ medicine a very real possibility. Professor Michèle Ramsay, Director of the Sydney Brenner Institute for Molecular Bioscience (SBIMB), explains: “At the moment, the most broadly effective drug for any given condition is usually prescribed to most patients. So, if there are five drugs available for a condition, doctors prescribe the one that usually works for the majority. But people are very different – some will respond well, others will see little effect, and others could suffer serious side effects.”

The results could be disastrous. One 2015 study of four South African hospitals, for example, showed that 16% of hospital deaths are related to adverse drug reactions.

Pharmacogenomics aims to take the guesswork out of prescribing, by looking at genetic variants that determine how a person will metabolise and respond to a drug.

This is especially important locally, adds Ramsay. “We need more data to apply precision medicine in African populations. There’s a lot of data available on European and Asian populations, but these studies wouldn’t necessarily be relevant in an African context.”

Available studies confirm this. Collen Masimirembwa, Distinguished Professor at the SBIMB, showed that side effects of the HIV drug Efavirenz (EFV), which include rashes, depression, and even suicidal tendencies, are more commonly observed in African patients on a standard dose of 600mg/day. Many people in Zimbabwe and Botswana also have a gene variant that increases the metabolism of EFV and renders the standard dose toxic when it is administered.

Following this discovery, lower doses led to increased compliance and better viral control. In Botswana, too, genomic studies showed that about 13.5% of the population would be unable to effectively utilise EFV-based therapies, leading  to a change in the country’s HIV management policy in favour of dolutegravir.

Masimirembwa is currently also working on similar studies to look at the effects in African populations of the breast cancer drug Tamoxifen as well as certain tuberculosis and malaria drugs. Ramsay hopes that the practical application of some of this research could be as close as two or three years away.

Kuda Nyamupa, a PhD candidate at the SBIMB, is also working on a new pharmacogenetics-guided treatment algorithm for hypertension in black South Africans. His research involves 600 patients from Soweto and the goal is to develop a guide for health practitioners to discern what medications and dosages to use for these patients. This decision is not only influenced by genes, he says, but also by other factors such as age, body mass, activity levels and alcohol use.

“We don’t apply the term ‘one size fits all’ to most facets of our lives and yet we take this approach with medication. In the future, this will change. As genetic testing becomes more common and readily available, especially in Africa, medicine will become personalised and much more effective,” says Nyamupa.

  • Delia du Toit is a freelance writer.
  • This article first appeared in Curiosity, a research magazine produced byWits Communications and the Research Office
  • Read more in the 16th issue, themed: #Drugs, where we highlight the diversity, scope, and multi-dimensional nature of drug-related research at Wits University.