Neurodegenerative disease damage reversed in fruit flies

Alzheimer's and Parkinson's symptoms have been reversed in fruit flies following treatment with a drug-like chemical, says research published in the Proceedings of the National Academy of Sciences.

Scientists are making progressing in techniques to protect nerve cells.

May 1, 2016

The discovery, which centers around the protection of brain cells, could be a turning point in the fight against neurodegenerative disease, say the authors.

Neurodegenerative diseases occur when groups of nerve cells in the brain die, making it difficult for a person to move and to think.

ccording to Claire Bale, of Parkinson's UK, the symptoms of Parkinson's tend not to appear until 70 percent of nerve cells in the brain have already been lost.

Unfortunately, current treatments are only able to tackle the symptoms of the condition - they cannot slow or stop the degeneration of these cells.

Researchers led by Dr. Carlo Breda, of the laboratory of Prof. Flaviano Giorgini at the University of Leicester in the United Kingdom, wanted to gain a better understanding of how this kind of disease starts and how it progresses.

Reducing metabolites decreases the symptoms of neurdenegeration

The team used the fruit fly Drosophila melanogaster to investigate how metabolites in the kynurenine pathway contribute to a loss of nerve cells in Alzheimer's disease, Huntington's disease, and Parkinson's disease.

Metabolites are substances produced during metabolism or other chemical processes in the body.

The scientists showed that genetic and pharmacological strategies can be used to lower levels of toxic metabolites in the nervous system. The result was a reduction in a number of the symptoms of neurodegeneration.

Previous studies have shown that certain metabolites are more common in people with neurodegenerative disease, and that they are poisonous to nerve cells.

Genetic approaches have successfully prevented the activity of two critical enzymes in the kynurenine pathway, known as TDO and KMO. This reduced the amount of toxic metabolites and led to a decrease in nerve cell loss in Huntington's disease in a fruit fly model.

In the current study, the authors found that inhibiting these two enzymes led to an improvement in symptoms in the flies. This was due to increased levels of kynurenic acid.

Kynurenic acid is a "protective" kynurenine pathway metabolite that counters the effects of the toxic metabolites.

Prof. Giorgini, of the Department of Genetics at Leicester, explains that there is a fine balance between levels of "good" and "bad" metabolites in the kynurenine pathway.

When neurodegenerative disease occurs, the balance shifts toward the "bad." By inhibiting TDO or KMO, the scientists moved the balance back to "good," he says.

In flies with Huntington's, inhibiting TDO or KMO meant that newer neuron cells were lost. Flies with Alzheimer's or Parkinson's had a longer lifespan than expected, and they recovered some of their ability to move.

Hope for future therapy

The team also succeeded in reducing symptoms by using a drug-like chemical to inhibit TDO.

"The two most common neurodegenerative disorders worldwide are Alzheimer's and Parkinson's disease. The treatment options for these diseases are limited, and to date no cures exist. 

Our hope is that by improving our knowledge of how these nerve cells become sick and die in the brain, we can help devise ways to interfere with these processes, and thereby either delay disease onset or prevent disease altogether."

Prof. Giorgini

As more people live longer, these devastating neurodegenerative diseases will become more common. The authors hope that their work might contribute to the development of drugs to treat such disorders in future. 

Prof. Giorgioni says the next step will be to confirm the results in mammals, and then to carry out clinical trials to see if the approach could help patients.

Bale, head of research communications at Parkinson's UK, which was one of the organizations supporting this trial, says: "There is a lot of potential in harnessing the power of protective proteins to prevent brain cell loss."