Midlife crisis? Flies offer hope of cure

PUBLISHED : Sunday, 26 March, 2006, 12:00am
UPDATED : Sunday, 26 March, 2006, 12:00am

A group of newly discovered genetic diseases that strike people in midlife - causing uncontrolled movements, loss of cognitive function and emotional disturbances - may soon be cured thanks to the help of fruit flies and a Hong Kong biochemist.

According to the Department of Health, polyglutamine diseases - nine conditions caused by stretches of DNA in a gene that contain the same trinucleotide sequence repeated many times - started appearing in Hong Kong in 2000.

The most common versions include Huntington's Disease, Kennedy's Disease and various types of spinocerebellar ataxia. They all have different symptoms, but share the same cause. Mild forms of the disorders become more severe as they pass from one generation to the next.

'Multiple members in more than 90 families have been found to suffer from the diseases. We believe, as people live longer, more cases will be discovered - especially with the way DNA testing has developed,' said a Department of Health spokesman.

'It happens to adults. People start to lose their motor skills and sense of balance. It keeps getting worse over time. It cannot be cured or controlled by drugs.'

There may be no cure, but Chinese University biochemist Edwin Chan Ho-yin is close to finding a way to stop the disease progressing, with the help of a genus of fruit fly called Drosophila. It shares more than 60 per cent of human disease genes.

Dr Chan, who began by focusing on Huntington's Disease, explained that the gene responsible for the disease was caused by an expansion of the CAG DNA sequence.

'Most normal people have less than 40 repeated CAGs,' he said. 'If you have more, the protein that the CAG sequence produces - glutamine - will also expand.

'The polyglutamine ends up unable to be folded properly, aggregates and eventually forms large, clump-like inclusions.'

'This affects different proteins in different versions of the disease. But, in general, the more expansion there is, the earlier the onset of disease and the more severe it is.'

Using fruit flies, Dr Chan discovered a special protein that could help fix the incorrectly folded polyglutamine.

'HSP70 is a chaperone protein that helps fold proteins properly,' he said.

'By manipulating it, we can reduce the effects of polyglutamine diseases.'

He said the results were published in September.

Dr Chan, who is working with the Harvard Medical School, also found that polyglutamine tends to enter the nucleus of cells.

He believes this is key to how the protein causes neurological dysfunction.

Through testing which genes are responsible for helping the protein to enter the nucleus - by deleting a single gene each time to see what happens - the biochemist hopes to work out a way to prevent polyglutamine from entering the nucleus.

As a result, the progress of the disease can be stopped and the severity of symptoms reduced.

Preliminary tests have been promising, but final results will not be in until the end of June.