Research by University College London (UCL) scientists could lead to the development of more effective drugs for treating manic depression thanks to a new screening approach developed in a "slime mould" - a microbe that lives in leaves and dung on forest floors.
The breakthrough using slime mould (Dictyostelium) is the first possible alternative to the current - accidental - method of discovering manic depression drugs. The findings are published today in the May 2005 issue of Molecular Pharmacology.
This research, carried out by a team led by Dr Robin Williams of the UCL Department of Biology, describes how the team tested variants of current drugs on the market in slime mould. It represents a first step towards the development of a scientific system for testing new treatments for manic depression. "Manic depression drugs on the market today have always been found serendipitously," says Dr Williams. "Lithium was originally proposed as a treatment for gout in the late 1800s and by chance, it was later found that it helped balance moods and is now the most widely used manic depression drug on the market. Valproic acid, another drug commonly used to treat both epilepsy and manic depression, was also found accidentally, as it was initially used as a solvent for dissolving epilepsy drugs.
"With these results, we can now identify new compounds which we hope will have the same effect as other manic depression treatments without unwanted side effects. We are testing this using a simple microbe - a slime mould - which is much faster, easier and more reliable to use than human nerve cells."
Current manic depression drugs like valproic acid have side-effects - an increased chance of liver damage, an increase in the chance of birth defects (embryonic malformations) if taken by mothers during the first trimester of pregnancy and may increase HIV infection. However, developing alternative manic depression drugs has so far proved impossible.
The scientists hope that their screening system, which involves testing possible drugs in slime mould and looking for a chemical change, will provide an important scientific building block that could lead to a better and safer range of manic depression drugs. The team is currently developing variants of valproic acid that they expect will have fewer harmful side-effects.
The origins of Dr Williams' work in this field were set out in Nature in 2002, when he found a protein which may be involved in causing manic depression, called prolyl oligopeptidase. This protein is present in both slime mould and the mammalian nervous system - and according to a number of teams the protein functions abnormally in manic depressed patients.