New treatments for African trypanosomiasis (aka African Sleeping Sickness) have been a hot topic for university research and not for profit organisations for over a decade, with potential drug targets being discovered and celebrated on an almost yearly basis. Although four drugs are already been registered for the treatment of African trypanosomiasis, all have extreme side effects and require complex administration regiments (which is far from ideal in locations where the disease is prevalent).
For decades it has been known that messenger RNA (mRNA) “decapping” (the removal of a chemical moiety, 7-methyl-guanosine) is performed by the nudix domain proteins in yeast, mammals, plants and most protozoa. However, the one marked exception is the family of protozoa, which includes the highly pathogenic trypanosomes and Leishmania. Neither have homologues to any of the nudix domain proteins or any of the major decapping ancillary proteins. Although it was envisaged that mRNA decapping still occurs in these organisms, the way in which it happened remained completely unknown.
Researchers at the Biocentre of the Julius-Maximilians-Universität (JMU), Germany, have recently reported an exciting new development. A new enzyme, called ApaH-like phosphatase (“ALPH1”) has been identified in trypanosomes and is thought to be the missing piece in the mRNA decapping puzzle. This new enzyme is causing hype because it does not exist in humans – making it an attractive target for drug development. Finding enzyme targets that have do not exist in the host animal is beneficial in drug development, as there is no worry that the drug will also have negative activity on a similar host isoform.
The ALPH1 enzyme functions to degrade the trypanosome messenger RNA, similar (in activity, but not in structure) to the nudix domain proteins. The JMU researchers reported that ALPH1 is essential for trypanosome viability and therefore potentially presents itself as the next major drug target against human diseases caused by Trypanosomiasis or Leishmaniasis.