new approach

[mschild <mmoo@xxxxxxxxxxx>]

Monday, 01 June 2009 

development of a new drug to treat
Parkinson's disease.

New nuclear-based research from Australian Nuclear Science and Technology 
Organisation (ANSTO) has focussed on a protein called Alpha-Synuclein, which 
plays a role in the development of Parkinsonâs disease when it behaves 
abnormally. This behaviour can be stopped or even reversed using a man-made 
polymer called a dendrimer, also known as a âdense starâ polymer. 
This fundamental research adds another piece in the puzzle to develop better 
treatments for Parkinsonâs disease, which affects around one in 250 
Australians. 
ANSTO Researcher, Dr Agata Rekas, said that past research had shown the 
dendrimer â called a PAMAM dendrimer and made by Dendirtech Inc - had 
positively affected a peptide involved in Alzheimerâs disease (ABeta) and a 
prion peptide. So Dr Rekas and Dr Seok Il Yun, an ANSTO Post Doctoral fellow, 
decided to see if it had a similar effect on the Parkinsonâs disease. 
âAs all these diseases affect the brain and neuronal pathways in the body we 
anticipated the dendrimerâs effect would be similar, and we were right,â 
she 
said. 
âThe Alpha-Synuclein protein is a natural protein in the body but when it 
aggregates into fibrils, long insoluble strings of protein molecules stuck 
together, it affects transmissions to the brain, resulting in Parkinsonâs 
disease,â Dr Rekas explained. âNo one is sure of the proteinâs normal 
role but 
we believe it assists cognitive function. 
âIt is thought that the aggregation is triggered by a dopamine deficiency and 
causes deposits in the brain to occur, however this could be just a factor, 
not the complete cause, of the disease,â she said. âThere is still much to 
find out, but itâs all part of the puzzle. The exciting part of our results 
is 
that it most definitely provides further information as to how this dendrimer 
can contribute to developing better therapeutics for Parkinsonâs disease,â 
she 
said. 
Dr Rekas explained that a dendrimer is spherical in shape and contains 
chemical groups similar to those of proteins, which start branching out in the 
middle so the dendrimer increased in size as each layer was added, similar to 
the branch-like structures seen in snow flakes. 
âThe more layers in the dendrimer the more effective it was due to the larger 
surface area. In the experiments we put certain amounts of these dendrimers 
and a control, with no dendrimers, into a protein solution for over 120 hours 
and stimulated aggregation with heat and shaking,â she explained. âThe 
control 
measured a lot of fibrils and different dendrimers reduced this fibrillar 
growth to various extents. 
âWe used an electron microscope to look at what was physically happening and 
verified the results using small angle neutron scattering, where a neutron 
beam passes through the sample onto a detector giving information as to 
whatâs 
occurring at the molecular level, âshe said. âThe neutron experiments were 
conducted by Dr Yun. 
âThe results clearly showed that the larger dendrimer inhibited the abnormal 
activity of the protein best. This information can now be used by drug 
companies focussed on treating Parkinsonâs so the next stage would be for 
such 
companies to develop this research further,â she concluded. 


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