What would it take to build an African drug discovery ecosystem?
Africa has great potential for drug discovery. The continent has natural resources, indigenous knowledge and human capacities. And he needs it: he bears more than 20% of the global burden of disease. There are many African scientists undertake cutting-edge research. But lack of resources makes it difficult to conduct world-class science. A team of African biochemists, cell biologists and bioinformaticians share some thoughts on what it would take to establish an Africa-wide drug discovery ecosystem. The authors are leading members of the COVIDRUG-AFRICA Consortium—the consortium for the rapid development of drugs against COVID-19 in Africa.
What are the challenges of drug discovery?
Access to infrastructure, long-term financing and supply chain constraints are some of the challenges.
In South Africa, research and development (R&D) expenditure as a percentage of GDP is down—0.62% in 2019-2020, compared to 0.69% in 2018-2019. Most of this funding comes from the government. Business investment and other R&D have also decreases during the last years.
For many other African countries, R&D expenditure is non-existent. China, the United States, Israel and Germany, on the other hand, spend on average between 2% and 4% of their GDP on R&D. These countries are among the major drug producers.
Drug discovery research in Africa receives small but essential grants international funding through philanthropy foundations and selected pharmaceutical companies. However, substantial and targeted long-term funding initiatives are rare. An exception is the H3D Center at the University of Cape Town in South Africa. He did pioneering work in collaboration with the Malaria drugs on a promising new antimalarial compound.
Fundraising is often limited to specifically associated diseases with Africa. The unintended consequence is that the scale of research supported in some countries of the world cannot be matched in Africa. This can stifle innovation.
Another factor holding back African research is the lack of strong collaborative networks between African laboratories and institutions. This is largely due to university policies and limited funding.
An often overlooked barrier to drug discovery is the inefficient supply chain for reagents and consumables on the continent. The long lead times and administrative burden associated with sourcing and obtaining chemicals often means that promising projects become unfeasible.
Where are the problems in the process?
To understand pain points and opportunities, it helps to look at the drug discovery process.
The first phase consists of generating collections of chemical compounds. This is achieved using synthetic chemistry, extraction from natural sources. It can also be done by identifying promising compounds for reuse using computational methods. Promising compounds are subjected to laboratory analyzes to predict their potential behavior in the body and their suitability as drugs. There is little activity in this area in African countries. The main reason is the lack of infrastructure. Researchers lack the advanced analytical instrumentation required for testing.
The first phase of the drug discovery process is followed by animal testing and further preclinical evaluation of compounds. The final phase consists of clinical trials on human subjects. Costs and infrastructure requirements increase as the process progresses.
There is room for significant improvement in all of these aspects. But perhaps the most pressing need is to expand synthetic chemistry capacity beyond South Africa. What hinders this is mainly access to infrastructure.
A workable strategy would involve strengthening the initial phase of the pipeline and then collaborating in later phases. This approach is likely to succeed and inspire confidence in funders to invest more in building sustainable drug research capacity.
Additionally, governments could dedicate a fraction of their GDP to support research and development and facilitate customs clearance of chemicals and reagents and make it economically attractive for suppliers to establish local entities.
Why not let the rich countries do this job?
Pharmaceutical companies mainly focus on diseases that strongly affect the western world due to the substantial financial returns. Additionally, they have a financial incentive to focus on drugs for chronic conditions that require persistent or lifelong commitment from patients. Diseases that primarily affect Africa, including Infectious diseasesare at the back of the queue for pharmaceutical laboratories.
The COVID-19 pandemic has shown that in times of crisis, developed countries will put their citizens first. African self-sufficiency in vaccines and chemotherapy is therefore vital.
The growing resistance of pathogens to existing treatments for endemic diseases is another reason to pursue drug discovery.
Africa’s stock of indigenous knowledge, combined with natural resources not found elsewhere, creates an opportunity for natural drug discovery.
Organisms may contain various chemotypes of compounds that are absent from commonly used synthetic compound collections for discovery purposes. About four decades ago, more than 80% of drugs came primarily from natural product sources or were synthetically modified from natural compounds. Recent Data indicate that nearly half of the drugs approved since 1994 are still based on natural products. And there are plenty of other natural springs to explore.
Another reason why African countries are looking for new drugs is the genetic diversity-Which one is higher than other regions. Populations may differ in their sensitivity or tolerance to a particular drug treatment. African populations also possess a number of genetic adaptations that have evolved in response to various climates and diets, as well as exposure to infectious diseases.
Even minor genetic differences could affect the drug pharmacokinetics, including impaired drug metabolism that results in decreased therapeutic response and increased toxicity. There is also a socio-economic case to be made for accommodating and expanding drug discovery programs in Africa. Stronger drug discovery capability could produce companies serving various aspects of the pharmaceutical development pipeline. It would be an economic stimulus.
A multinational consortium of scientists could dramatically increase capacity in Africa for all aspects of drug discovery for the continent’s current and future diseases.
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