Advances made in Parkinson's research
understanding of neurones controlling movement and coordination and
their malfunction and death in Parkinson's Disease has lead to the
possibility of a drug therapy that halts disease progression.
The study of gene expression is increasingly important as it gives researchers clues to the molecular mechanisms involved in many disease processes and can lead to a greater understanding of the nature of disease.
With more than one million sufferers in the US increased understanding of the cause and progression of Parkinson's disease may ultimately bring researchers closer to a viable therapy that treats on a genetic level rather than the disease's symptoms.
This latest discovery has been made possible by the use of GE Healthcare's CodeLink bioarrays, enabling researchers in pharma, biotech and academia to compare the expression level of thousands of live cell actions in a single experiment, rather than examining individual gene activities one at a time.
A spokeswoman for GE Healthcare told DrugResearcher.com: "CodeLink can be used to track changes in gene expression when tissue samples are treated with a potential drug candidate-to determine if a product in development has potential therapeutic value."
"CodeLink will play a pivotal role in evaluating a person's genetic profile and determining if they are likely to respond to a given therapy or not."
The heart of the system is the CodeLink slide, which is coated with a proprietary 3-D matrix that suspends the genetic material being evaluated. This is referred to as the oligonucleotide probes. The matrix on the slide is a critical part of the technology allowing greater target access to the genetic material, a key advantage over two-dimensional surfaces, and hence greater sensitivity. The probes are arrayed at very high density.
Failure to treat Parkinson's can result in poor symptomatic control and the wrong treatment can cause unnecessary side effects. Dr. Howard J. Federoff, Director of the centre for ageing and developmental biology at the University of Rochester said: "CodeLink allowed us to detect gene expression changes previously undetectable. As a result, we were able to observe small yet significant changes relating to neuron function."
In this preclinical study, researchers administered a neurotoxicant (MPTP), a known inducer of Parkinson's and then used a CodeLink UniSet Mouse I Bioarray and CodeLink Scanning and Expression Analysis software to study the gene expression of MPTP treated genes in the substantia nigra (SN) portion of the brain.
Analysis detected dysregulation of genes in three main areas related to neuron function: cytoskeletal stability and maintenance, synaptic integrity, and the life cycle of the cell and apoptosis, the naturally occurring process of cellular death.
CodeLink's UniSet Mouse l Bioarray contains DNA probes spotted onto a prepared glass slide, with each probe representing one of about 10,000 mouse genes. By adding an RNA sample prepared from mouse tissue to the bioarray, scientists are able to determine which genes are expressed, or active, in the tissue sample and to measure the level of gene activity.
The spokeswoman added: "With 54,841 gene targets, the new CodeLink Human Whole Genome Bioarray has the highest content of any commercially available human microarray on a single chip."
"This high density significantly improves productivity by consolidating genome-wide expression profiling into a single microarray experiment. The majority of this content has been functionally validated to ensure each experiment generates the most biologically meaningful results."
With sensitivity to detecting transcripts at a level of 1:900,000 (around 0.3 copies per cell). This enables researchers to detect genes expressed at very low levels.
The CodeLink Bioarray can also be used wherever researchers want to study changes in gene expression. Currently, other users of the Codelink technology include the US Environmental Protection Agency who are performing gene expression experiments aimed at identifying biomarkers to assess aquatic toxicity.
CodeLink is one of the key technologies comprising GE Healthcare's new Molecular Diagnostics Division launched in August 2004 to develop in-vitro clinical diagnostic-based solutions.
