Scientists have discovered a new cure for sleeping sickness, a fatal infection spread by the tsetse fly and linked to the deaths of more than 40,000 people per year in Africa.
Initially, the disease, which is caused by a parasite called Trypanosomiasis brucei, presents with fevers, headaches, joint pains and swollen lymph glands. Untreated, it progresses to anaemia, kidney and heart damage and, finally, invasion of the nervous system. This latter stage is associated with disturbance of the sleep-wake cycle, fatigue, confusion and, eventually, death.
Unfortunately, the only effective treatments, which include an arsenic-based drug, cause severe side effects for some and are just unavailable for the majority.
But now, writing in Nature, Dundee University researcher Julie Frearson and her colleagues have identified a powerful drug that can cure experimentally-infected mice.
The researchers discovered the drug by homing in on an enzyme called NMT - N-myristoyltransferase - which plays a crucial role in allowing important proteins to associate themselves with cell membranes.
Crucially, knocking out this enzyme is fatal for the parasite, so the team commenced a search for molecules that could block it selectively without affecting the mammalian equivalent of the enzyme.
By screening 62,000 chemical structures, the Dundee scientists identified some molecular "hits" that they then further chemically tweaked to make them highly selective for the parasite form of NMT.
One such resulting molecule, DDD85646, was tested in mice infected with sleeping sickness. All of them responded and tests showed that the drug had killed, rather than just disabled, the parasites.
Alas, this compound doesn't penetrate the nervous system very effectively, which is a major priority for treating advanced cases of sleeping sickness, but it nonetheless acts as a powerful starting point for the development of more brain-active forms of the drug to treat what's currently regarded as a "neglected tropical disease."