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Does US Mad Cow Disease Present an Opportunity for Microarray Industry?

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The discovery in the US of one slaughtered Holstein affected with bovine spongiform encephalopathy, or mad cow disease, has raised the question of how this threat to the safety of the country’s food supply, and an important industry, might be mitigated. And, for the microarray industry it asks: Does this situation present an opportunity to apply microarray technology to the diagnosis of the disease at an early stage -- before an animal enters the food supply?

A UK-based reference lab on Dec. 25 confirmed a Dec. 23 preliminary diagnosis of the presence of BSE in a cow butchered Dec. 9 in a Washington State slaughterhouse, the United States Department of Agriculture said Monday, after issuing a Class II recall for the facility’s entire day’s production, while cautioning that there is a low likelihood that the recalled beef contains any of the infectious agent that causes BSE.

The news sent spasms through the global food chain, as more than 24 countries suspended the importing of US beef, while US consumers in at least 9 western states fretted about the consequences of having eaten suspect beef. And, the time lag between the slaughter of the cow and the confirmation of the diagnosis clearly demonstrates the need for speedier answers to such important queries.

It’s a situation that somewhat parallels last year’s SARS epidemic, when the microarray industry leaped at the opportunity and created a number of microarray-based applications for diagnosis of the new disease as part of a remarkable global scientific collaboration.

Thus far, the microarray community has been slow to respond, perhaps due to the holidays, or the fact that the disease has been well-studied in Europe for close to two decades.

Today, there are no commercial microarray-based tests that can detect the presence of BSE in an animal or in the meat supply. But with this new health threat now landing in the US, the microarray industry is watching developments.

Hercules, Calif.-based Bio-Rad is considered the world leader in testing for BSE and other prion-based diseases, with over 60 percent of BSE screenings performed with its test, which was developed in collaboration with the CEA, France’s Atomic Energy Commission and is one of five tests approved in Europe.

Bio-Rad provides the two-stage Platelia BSE test, which specifically detects the abnormal form of the PrP protein, called PrPres. In the test, according to the Bio-Rad website, PrPres is taken from post-mortem bovine brain tissue, and is selectively purified through a process involving, in particular, treatment with proteinase K under such conditions that normal PrP (PrPsens) undergoes total degradation, whereas most of the PrPres immunoreactivity is retained. The soluble PrPres is then measured using the DAS-ELISA immuno-metric assay in the second stage of the process, which takes about four hours in total.

The Bio-Rad test is available in the UK, France, Germany, Belgium, Luxembourg, Netherlands, Norway, Sweden, Switzerland, Italy, as well as Spain.

Robin Stears, marketing manager, microarray business unit, for Bio-Rad Laboratories, and the former senior scientist for microarray concern ArrayIt, told BioArray News, that the company has no current plans to develop a microarray-based test for the disease.

Others in the industry seem to agree.

Tom Vasicek, vice president of business development for Lynx Technologies, which performs gene-expression profiling on its Massively Parallel Signature Sequencing system, said that transcription profiling might not be the answer to detecting this disease.

“BSE has been very heavily studied for the last 20 plus years,” he said. “We know what it is and we already know so much about the proteins involved, so that is where you want to be in almost every disease study, if you can get there. MPSS could detect it better than anything else in the world, no question, if it resulted in a transcriptional change. It’s really something that lends itself better to protein tests, than to a transcriptional test.”

Paul Predki, vice president of research and development for the protein microarray company Protometrix of Branford, Conn., said this disease might not be suited for microarray diagnosis.

“Is it the most practical use of the technology, does it take advantage of the technology?” asked Predki. “I don’t think it does. If you just have one antibody, you can do a standard ELISA test. The advantage of a microarray is you could have a large number of antibodies on the array and do a large number of assays in parallel. For one, or a limited number of antibodies, the parallelization of antibodies is not too important.”

In Europe, another technology is being tested in the abbatoir, a surface plasmon resonance technology being developed by Biacore (see BAN 11/29/2002).

But while the immediate crisis involves BSE in animals, gene expression profiling may in the future offer means for study or even detection of variant Creutzfeldt-Jakob disease, the human neurodegenerative illness that sometimes results from ingestion of BSE-contaminated products. As with different cancers, this variant Creutzfeldt-Jakob disease could present unique gene expression signatures that enable physicians to distinguish it from other types of Creutzfeldt-Jakob disease that are hereditary or result from causes other than exposure to infected cattle.

The disease, which has been rare so far in the UK, where the bulk of the BSE cases have occurred, has an average incubation period of as much as 20 years. So far variant CJD cases have been limited to people who are homozygous for methionine at codon 129 of the “prion” gene, according to a 2001 review article on BSE in the British Medical Journal. If this finding proves to hold true, and CJD increases in the US, array-based genotyping platforms may want to add this test to their lineup.

Dragan Momcilovic, a scientist at the US Food and Drug Administration’s Center for Veterinary Medicine who has spent the last four years on BSE research focused on the detection and analysis of animal materials in food and feed, sees opportunities for microarray or biochip technology to make an impact on detecting prohibited materials in animal feeds, a vector for the transmission of BSE.

“There are so many analyses that could be done in one run using microarrays,” he said.

Animal feeds can contain a very complex matrix of materials that need to be individually identified, he said. “You could store information on a biochip that would [determine] animal species and animal classes, and additional information on DNA material for plants, since ruminant seed is plant protein.”

For diagnosing the disease in animals, any potential application of microarrays — of protein or DNA — is dependent on the further development of science, he said.

“The issue to be resolved is the need for more monoclonal antibodies specific to the [BSE] monoclonal antibody,” he said. “Current antibodies are not specific – you don’t know if it is normal or abnormal. If microarrays are to be useful, there need to be enough antibodies to perform the assay.”

—MOK

 

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