Raising enzyme levels may help treat PD (enzyme controlled by gaucher gene)
 

Raising an Enzyme's Levels May Help Treat Parkinson's Disease

- Feb 22 2013
http://www.pdf.org/en/science_news/r.../pr_1361552717

Increasing the amount of glucocerebrosidase (GBA enzyme) in the brain
may help to treat Parkinson's disease ... may
also help keep harmful deposits of the protein alpha-synuclein from
accumulating in the brain.

Previous observations suggested a link between a deficiency in the GBA
enzyme and PD. For example, people with PD typically have lower
amounts of GBA enzyme in their brains. Some people living with PD also
have mutations in the GBA1 gene, which makes this enzyme and causes
Gaucher's, a disease which can include PD-like symptoms...

... They studied the concept, using two
mouse models: mice with symptoms of Gaucher's disease and other mice
with PD-like symptoms. Researchers treated mice with gene therapy - an
injection of healthy copies of the GBA1 gene...

Results

Six months after the gene therapy treatment, the mice with symptom's
of Gaucher's disease, had reduced fatty deposits in the brain and
fewer clumps of misfolded alpha-synuclein and other proteins
associated with nuerological disorders. The treatment also restored
the impaired memory of these mice to normal levels.
Like people with PD, mice treated to have PD-like symptoms had lower
amounts of active GBA enzyme than normal mice. Mice with the highest
levels of alpha-synuclein had the lowest levels of GBA enzyme.
In the PD mice, the gene therapy treatment decreased the amount of
free alpha-synuclein in the brain, but not of alpha-synuclein clumps.
What Does It Mean?

This study adds to existing evidence that a deficiency in the GBA
enzyme may contribute to PD symptoms. It also suggest that fixing this
deficiency could be therapeutic...
...It is possible that the enzyme
normally clears out excess alpha-synuclein, that it helps the protein
fold properly to prevent its clumping together, or that is breaks up
protein clumps. Further studies are needed to determine the precise
role of the enzyme in PD...

Reference: Sardi SP, Clarke J, Viel C, Chan M, Tamsett TJ, Treleaven
CM, Bu J, Sweet L, Passini MA, Dodge JC, Yu WH, Sidman RL, Cheng SH,
Shihabuddin LS (2013) Augmenting CNS glucocerebrosidase activity as a
therapeutic strategy for parkinsonism and other Gaucher-related
synucleinopathies. Proceedings of the National Academy of
Sciences:1-6.