In another step toward creating new
treatments for Parkinson's disease, researchers at Harvard Medical School in
Massachusetts have engineered fruit flies that express a human gene linked to
the disease.
The accomplishment is exciting, Dr. Mel B. Feany told Reuters Health,
because the fruit fly's genetic makeup and short life span make them ideal for
discovering new Parkinson's-related genes and for screening potential drugs.
Feany and her colleague, Dr. Welcome W. Bender, report their findings in the
March 23rd issue of the journal Nature.
With the recent success of other researchers in creating a mouse model for
Parkinson's, Feany said both animal models should speed the development of drugs
that prevent or slow the progress of the disease. Current treatments, she noted,
only relieve symptoms.
A slow degeneration of the brain, Parkinson's usually strikes people older
than age 60, but can affect younger adults. The disease causes muscle spasms and
stiffness; movement is difficult, and when they are not moving, patients suffer
tremors. The cause of Parkinson's remains unclear, but patients' brains show
changes, such as specific protein accumulations, known as Lewy bodies. In
addition, brain cells that produce the chemical messenger dopamine gradually die
off.
Until recently, Parkinson's research was hindered by the fact that no gene
had been linked to the disease process. Then researchers discovered that a small
percentage of Parkinson's cases showed mutations in a gene that produces a
protein called alpha-synuclein. This protein is the main component of the Lewy
bodies seen in nearly all cases of Parkinson's.
Feany and Bender used three versions of the alpha-synuclein gene -- two
mutant and one normal -- in their fruit flies. The investigators discovered that
as the flies aged, they developed Parkinson-like physical traits: they began to
lose dopamine-producing brain cells and showed Lewy-body-like accumulations that
contained alpha-synuclein protein. Climbing tests showed the behavioral traits
were also there, as older fruit flies often fell when climbing to the top of a
vial.
Both the mutant and normal gene variants had these debilitating effects, and
Feany noted that only people with a familial (inherited) form of Parkinson's
have a mutation in the alpha-synuclein gene. The alpha-synuclein protein is
abundant in the central nervous system, but its function is unknown. Feany said
the protein's tendency to accumulate may be what kills off dopamine-producing
cells. She suspects that some people are vulnerable to developing Parkinson's
because of small mutations in other genes.
"We desperately need to understand how (brain cells) die in Parkinson's in
order to design rational drugs," she said.
Feany and other Harvard researchers are currently testing candidate drugs
for their effects on protein accumulation and brain-cell degeneration in the
fruit flies.
