When most people consider a rare disease, they think of genetic conditions such as cystic fibrosis or Huntington's disorder. However, in less developed countries there are many parasitic diseases which are also categorised as rare. Researchers in Liverpool have been working on a new treatment which could finally mean that two tropical disease, which are shown to be two of the leading causes for global disability, may finally have a treatment.
Both of the diseases being researched, river blindness and elephantiasis, are transmitted through insect bites. Despite being transmitted through different insect vectors, and being prominent in different geographies, the two diseases share a drug target which researchers at Liverpool hope to leverage to treat and cure these conditions.
Onchocerciasis (river blindness) is a caused by a parasitic worm, most commonly found in Africa and Yemen, transmitted to humans through repeated blackfly bites. Once bitten, the larvae of the parasitic worm migrates through the bloodstream to the eyes, and other organs. As the parasite goes through it's life cycle and dies it causes inflammation, leading to eye lesions and overtime blindness.
Lymphatic filariasis (elephantiasis) is caused by the filarial parasite, most commonly found across Asia, and is transmitted to humans through mosquitoes. Although usually acquired during childhood the affects of the lymphatic system damage, caused by the parasites, does not become apparent until later life. In chronic conditions we start to see the characteristic signs of the disease, where limbs begin to swell and harden due to the damaged lymphatic system being unable to move fluid through the body. This can lead to disability, and the associated social stigma that comes with this, deepening those affected into poverty.
Thanks to funding from the Bill and Melinda Gates foundation, steps have been taken to develop treatment for these reversible and treatable conditions. Investigators at the Liverpool School of Tropical Medicine started looking into potential drugs which are characterised as anti-wolbachia (the most common causes of both diseases), screening through over 400 analogues. Their novel synthetic drug AWZ1066S, showed great potency and specificity against the target pathogen, with high bio-availability. This high level of specificity means that the drug is unlikely to interact with healthy bacteria found in the gut (unlike the current group of anti-wolbachia treatments used today) whilst remaining highly effective against the two separate parasites. The high bio-availability also suggests that this drug will do well in an oral formulation, this could mean the development of a drug which will be cheaper to produce, easier to take and more accessible for areas which do not have electricity (a fundamental consideration when looking at the geographical distribution of these two diseases). Finally, the high potency means that the drug should effectively treat these two conditions in 7 days or less, again reducing the cost to those who affected by either disease.
Although this drug has only undergone pre-clinical testing, previous phase-I clinical trials using anti-wolbachia antibiotics suggest that this drug should be safe for humans, and this gives hope of a future treatment for these orphan diseases.
Previous proof-of-concept human trials showed that depleting Wolbachia using antibiotics may lead to safe outcomes. With AWZ1066S, a highly-specific anti-Wolbachia drug, the investigators targeted particular efficacy, safety, and drug metabolism/pharmacokinetic features. Because of its successful testing in preclinical models of infection, the potential treatment shows promise, the authors noted. It also has drug metabolism/pharmacokinetic properties that are compatible with a 7-days-or-less oral therapy.