New advance announced in fight against Alzheimers and Parkinsons
A five-year study by an international team led by Leicester has found a way of ‘reversing’ symptoms of neurodegenerative diseases such as Parkinson’s and Alzheimer’s – using fruit flies as test subjects.
The researchers have demonstrated that genetic and pharmacological approaches can be used to lower levels of toxic metabolites in the nervous system and thereby alleviate several symptoms of neurodegeneration.
The study, led by Dr Carlo Breda who works in the laboratory of Professor Flaviano Giorgini is published in the Proceedings of the National Academy of Sciences of the USA.
The newly published research utilized the common laboratory fruit fly Drosophila melanogaster in order to explore the role of specific metabolites in the kynurenine pathway that cause loss of nerve cells in models of Alzheimer’s, Parkinson’s, and Huntington’s diseases.
Past studies by the Leicester team and others have shown some of these metabolites are toxic to nerve cells, and their levels are increased in these diseases. In the past the researchers have found that they can use genetic approaches to inhibit (or “mute”) the activity of two critical enzymes in this pathway – TDO and KMO – which lowers levels of the toxic metabolites and reduces nerve cell loss in a fruit fly model of Huntington’s disease.
In the current study they have uncovered how inhibiting these two enzymes improves “symptoms” in flies because of increased levels of a “protective” kynurenine pathway metabolite known as kynurenic acid which counteracts the effects of the toxic metabolites.
Dr Breda said: “There is considerable interest in developing drugs that ‘turn down’ these enzymes, so our hope is that our work could lead to drugs to treat these devastating disorders in the future. Neurodegenerative disorders are devastating diseases with limited treatment options. The major risk factor for these diseases is aging – and as our society is becoming longer lived, we are facing dramatic increases in the number of individuals suffering from these disorders.”
Professor Giorgini added: “We are excited by these results, as they suggest that TDO and KMO inhibition could be a general strategy employed to improve symptoms in a myriad of neurodegenerative disorders, not just Parkinson’s and Alzheimer’s. Indeed, five years ago we first showed that these manipulations could improve “symptoms” in Huntington’s disease model flies, so our next step is to validate our work in mammalian models and ultimately to see if such drugs could be helpful to patients in clinical trials.”
For more background on Professor Giorgini's research see the below video: