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Q&A on drug discovery in SA

- By Kemantha Govender

Academics from around the world gathered for the European Molecular Biology Organization (EMBO) Global Exchange Lecture Course on Frontiers in innate Immunity and drug discovery at Wits from 6 until 10 July 2015.

 This conference reviewed the advances in innate immunity that can be exploited for drug discovery and development and also aimed to facilitate collaborative research between researchers.

 Dr Monde Ntwasa from the Wits School of Molecular and Cell Biology discusses how the conference touched on drug discovery in Africa.

Could you briefly tell us what the conference was about?

The conference fulfils an agreement between the EMBO and the Department of Science and Technology (DST) to promote interaction between South African scientists and their international counterparts. The audience for this are research students (Master, Doctoral and Postdoctoral) as well as principal investigators.

What are some of the most important things discussed?

What emerged during the week of excellent presentations centred mostly around TB and HIV but also on other interesting infectious diseases such as Listerosis, a bacterial infection that causes diseases of the central nervous system such as meningitis. It also affects immuno-compromised people such as pregnant women.

New studies involving the unique structure of the TB bug, known as Mycobacterium tuberculosis, were disclosed by a group led by Professor Jan Verschoor of the University of Pretoria. This new knowledge provides another opportunity to develop drugs against this difficult infection.

A suggestion to combat HIV resistance by targeting the host molecules that interact with the virus was mooted and stimulated new thinking about anti-HIV drug discovery. Another drug target that is emerging is a process called “autophagy” whereby a cell “eats” parts of its components to remodel itself when it experiences stress such as nutrient starvation. This is already considered to be a target in developing drugs against cancer but it is now emerging as a target in combating infections too.

New strategies to facilitate vaccine productions were also discussed. Vaccine development against HIV is particularly difficult and no effective vaccine has yet been produced. The innate immune system plays a key role in the development of antibodies and focus on it should be increased to produce appropriate antibodies required in anti-HIV vaccination.

What are some of the challenges faced by academics in drug discovery?

The major problem facing academics in drug discovery is that later stages of the process are extremely expensive and cannot be conducted without the involvement of pharmaceutical companies. These companies are, however, not primarily involved in charitable work. They get involved when success is almost guaranteed.

Academics are mostly active at the discovery of “lead compounds” which can then be developed further in partnerships with large pharmaceutical companies. The development of a drug past the discovery stage through clinical stages, on average, costs more than $2 billion.

Companies consider many aspects such as sustainability of the product before investing. That is why antibiotics are no longer considered a wise investment. Patients recover quickly once treated and the antibiotic stays in the shelf. The trouble is that the small range of antibiotics is becoming ineffective as bacteria have developed resistance to them. This is a major threat to humankind as insignificant infections would become fatal.

Patenting is the best way for academics to protect their discoveries but is too expensive. 

On the issue of regulating herbal medicine in SA, is this is still a problem and what are some of the thoughts on this subject? 

Many herbal mixtures contain the “active principle” or the therapeutic agent mixed with all kinds of toxic substances. These mixtures can therefore harm the individual when taken in uncontrolled doses. The task of the drug discovery process is to isolate the “active principle” and optimise its dosage for therapeutic purposes.

The reality is that the mixtures proliferate in commercial platforms such as some pharmaceutical stores without apparent measures to control their use. Even substances such  as the so-called herbal teas can have toxic effects. These are, however, freely available from the shops. The meeting felt that there is not adequate control of herbal mixtures. Anyone may put a mixture in a branded package and sell it easily in a supermarket store.

With regards to HIV and TB, what were some of the key points raised relating to drug discovery?

The most novel view here is  designing drugs that target the human physiology rather than the virus itself. This way resistance could be substantial reduced as mutation of the virus would have less impact. This also provides the opportunity to actually cure the infection as it could prevent it from even entering the cell. The virus can’t persist in the body if it can’t enter the human cell.

How are African countries faring in drug discovery and what are some of our biggest challenges and achievements?

Due to the high cost of the drug discovery process and the lack of venture capital, African countries have little chance of contributing significantly in the global activity. Sadly, we have huge natural endowment of potential drug sources from fauna and flora.

Our educational institutions are, however, making important contributions in developing “lead compounds”. These will require partnerships with large pharmaceuticals to develop further.

Why is it necessary for such conferences to take place?

This conference is meant to stimulate new thinking in research students and to share and scrutinise the latest developments in a highly specialised field. For us it is also crucial in fostering international collaborations.