Four for the price of one? This week Nature announced a paper that made a huge claim. A potential drug had been designed to treat four diseases that between them are responsible for 50000 deaths each year. Approximately 20 million people are affected by one of these conditions yet the discovery passed without so much of a whimper in the wider news. Only by trawling through the BBC News website could an article be found hidden away, nowhere near the top stories, and the evening news was instead filled with failed Olympic medal attempts.
Why is this drug not making the news? Advances in Alzheimer’s knowledge or a potential new cancer drug almost never fail to grab a headline. The answer lies in the diseases themselves; visceral and cutaneous leishmaniasis, Chagas disease and human African trypanosomiasis (sleeping sickness), caused by species of Leishmania and Trypanosoma parasites. You would be forgiven for not recognising them; the World Health Organisation dubs these Neglected Tropical Diseases (NTDs), mainly affecting people living in poverty at a huge financial cost to the developing nations. It’s easy to take a high ground and say that people simply do not care because they are not personally affected but it’s not as simple as that. Scientists have a responsibility to make their work understandable to the wider reader and in doing so bring such diseases into the spotlight. It is after all tricky to care about something that you didn’t know exists.
So what does this drug claim to do?
From the outset it’s important to note that all these experiments have been done using mice rather than humans so a degree of care is needed when considering how this might apply in ‘real life’. The results do however seem promising. The scientists screened 3 million different compounds before selecting a candidate that seemed to inhibit the growth of all four parasite species. They then individually modified certain structural features of the candidate to make it less toxic and to improve its ability to inhibit growth of Leishmania within macrophages, their host cell in humans.
From there the team infected mice with the different parasites and found that the drug performed at least as well as existing treatments with the benefit of being less toxic. They then wanted to pinpoint exactly what it was targeting and so spent 12 months growing the parasites in the presence of the drug to evolve resistance to it. Using whole genome sequencing they found a mutation in a complex called the proteasome, responsible for degrading unwanted proteins in the cell. This mutation prevented the drug from killing the parasite, indicating that this is how it functions. Importantly, the human proteasome is not affected.
So what does this mean for the future of NTDs? This is a huge, comprehensive study that has the potential to benefit thousands of people who suffer from not having a safe, effective treatment option. People can live infected by parasites for many years but they are continuously hindered by poor health and the impact that this has on their ability to work. The availability of a drug like this could really be life-changing so its performance in the preclinical toxicity studies will be of great interest.
Source – Khare et al. (2016). Proteasome inhibition for treatment of leishmaniasis, Chagas disease and sleeping sickness, Nature.