Hello my readers! This week, I plan to take you all on a journey that involves a bit of drugs, a bit of strange letter combinations and a lot of hope for those who are suffering from this pesky parasitic disease.
Sleeping sickness/Human African Trypanosomiasis (HAT) is a tropical disease that can be placed in the “neglected” category, quite sad to think about, right? HAT is caused by the unique parasite Trypanosoma brucei which is found commonly in two forms, Trypanosoma brucei gambiense & Trypanosoma brucei rhodesiense. Both of these forms are transmitted by the vector tsetse fly, which bites an individual and leaves a fatal mark if untreated (I’ll come back to this point about treatment in a second).
HAT is characterised in two stages whereby the first is acute and has the parasite residing mainly in the haemolymphatic system. The second stage is signified by the parasitic infiltration of the central nervous system (CNS), resulting in neurological defects, hence the name “Sleeping sickness”.
First stage treatment involves the use of the anti-parasitic agents pentamidine and suramin. However, if the parasite is crafty enough to gain access to brain tissue for the second stage, then the true effects of T.brucei infection come to light. Treating this stage is quite difficult as the options available (melarsoprol and eflornithine) are both toxic and limited in being able to cross the blood-brain barrier (BBB) to combat the parasites.
The lack of oral treatments for HAT led to an alternative treatment approach of using both nifurtimox and eflornithine in a combination therapy (NECT). Now this has shown some promise in reducing the effects shown in stage 2. However, this therapy still suffers from similar drawbacks to other treatment options, (i.e. requiring injections for eflornithine usage, toxicity issues when using eflornithine and finally cost).
So small, so miniscule and its bite is rather diminutive, but it’s this same bite that causes people on a large scale to be affected so significantly, people must wake up and see how this loss of human life must be addressed and sorted out!
Tsetse Fly image taken by J.E. Donelson, University of Iowa
Sleeping sickness image taken by Erwin van ‘t Land, MSF-Australia
A Waking Call For The Sleeping
One key point that I was driving at in my last blog post (nice little recap here) was the lack of investment for these neglected tropical diseases, but hope is on the horizon my readers.
In 2009, a Californian biopharmaceutical company called Anacor conducted a screening library of boron-containing compounds and found that these compounds are highly effective against T.brucei in the second stage of infection.
Further testing produced a result of a specific compound known as SCYX-7158 (try saying that five times in one go eh?). This was shown to be exceptionally effective against T.brucei as it could cross the BBB whilst requiring only one dose per day. Collaboration with several organisations including DNDi (Drugs for Neglected Diseases Initiative) and SCYNEXIS led to Phase I human trials launch in 2011.
After several years spent in rigorous clinical trials, it is confirmed that SCYX-7158 was successful in completing the Phase 1 human trials. No time is wasted in the DNDi and their partners proceeding into Phase 2b/Phase 3 clinical trials in 2016 in the Democratic Republic of Congo where 90% of all cases occur.
The potential of SCYX-7158 on treating sleeping sickness can go a long way than just causing smiles on these children’s faces, hope is a quality not to be squandered but rather cherished, keep smiling my friends, for a chance of sleeping sickness being eradicated is soon upon us.
Image taken by Sean Sutton, MAG
With a smile, I can feel encouraged that significant leaps are being made to treat sleeping sickness. As complicated as SCYX-7158 may sound, there is great confidence that it can serve as being the first oral-only single dose form of treatment. Not to put a downer on things, but whilst this is quite promising for treatment for sleeping sickness, more must be done to turn the NEGLECTED into RESPECTED.