Surgery News

BioGenes as new designated partner in EU funded dementia project

December 28, 2015

BioGenes will provide laboratory facilities and key personnel to develop specific monoclonal antibodies against novel neurochemical dementia biomarkers in blood and cerebrospinal fluid that have been identified during the project. These monoclonal antibodies may not only be used for diagnostics, but also have potential as therapeutic agents since they may access the CNS space.

Reliable differential clinical diagnosis of very early dementia stages is crucial for choosing the most effective therapeutic strategy. Recent research has demonstrated that multiparametric neurochemical dementia diagnostics (NDD) in cerebrospinal fluid does improve early and differential diagnosis of dementias.

cNEUPRO will establish European standard operation procedures (SOPs) for NDD and first NDD reference centres in Portugal and Hungary. cNEUPRO unites the forces of nineteen biotech and bioinformatic companies as well as leading clinical and proteomic dementia research centres.

Alzheimer's dementia is one of the most common brain diseases in the elderly, with about 5.7 million dementia patients in the EU25. Currently, no curative therapies are available. Although initial disease-modifying treatment strategies such as Abeta-immunisation have entered clinical trials, these novel treatments can only be most effective when offered at a very early stage of disease.

BioGenes GmbH specialises in highly sophisticated antibody and immunoassay development and has successfully developed monoclonal antibodies against all kinds of antigens: peptides, soluble proteins, membrane proteins, phosphorylated antigens, small organic molecules such as haptens, oligo- and polysaccharides, as well as highly toxic substances. An optimized mouse hybridoma technology allows BioGenes to produce monoclonal antibodies with antigen mixtures or small antigen amounts. BioGenes is certified to meet the international requirements and regulations of assured quality and animal welfare.

The researchers then dosed the mice with MPTP, a chemical that kills neurons in the substantia nigra and has become the major mechanism for studying Parkinson's disease in mice. The toxicity of MPTP was discovered in 1982, when young drug users in California developed the classic symptoms of Parkinson's disease, a disease that usually strikes those over age 60. Researchers found that the synthetic heroin these people had used was contaminated with MPTP, and further studies showed that MPTP is highly toxic to nerve cells in the substantia nigra.

When astrocytes make Nrf-2, the protein attaches to their DNA, kick-starting activity in hundreds of genes that release chemicals that can protect nearby neurons from oxidation ?? a series of chemical reactions that can injure or kill cells. "The astrocytes are also probably sucking up the bad stuff, thereby reducing the oxidative environment and stress on the neurons," says Johnson, adding that his laboratory is trying to identify those specific protective chemicals.

Nobody can predict when a manipulation of Nrf-2 could reach clinical trials, which Johnson says are at the very least two years in the future. While these experiments altered the mouse cells with genetic engineering, human trials would probably use drugs to boost Nrf-2 production in astrocytes. Several labs, including Johnson's, are already searching for candidate drugs.

The stakes are high, Johnson says, because Nrf-2 also protects brain cells in models of such fatal brain diseases as Alzheimer's, ALS, and Huntington's disease.

Normally, neurons die in these neurodegenerative diseases to "commit suicide" through a process called programmed cell death. "Nrf-2 seems to rebalance the system," Johnson says, "in favor of what we call programmed cell life."