Chronix Biomedical (San Jose, California) has now stockpiled enough evidence, including three new studies, that confirms fragments of DNA and RNA circulating in the blood have strong potential in the early diagnosis and prognosis of a variety of diseases, both in humans and animals.

That evidence will likely alter the diagnostic landscape in coming years.

The advances are made possible by massively parallel sequencing technologies, which allow for a new approach in the examination of plasma nucleic acids. The enabling technology, the Genome Sequencer FLX, is made by 454 Life Sciences (Branford, Connecticut).

The fragments, known as circulating nucleic acids (CNA), can accurately identify the presence of diseases in blood months or even years before the onset of symptoms. With this evidence, Chronix now is ready to outlicense its discoveries that make use of what may be the newest and most effective kind of biomarker around that could potentially result in a cascade of new tests.

"We've identified the disease targets for potential partners," Chronix CEO Howard Urnovitz told Medical Device Daily. "Any other company doing single nucleotide polymorphisms (SNP) tests is our competitor. But it's highly restricted and measures the past and not the present. SNPs tell you what your history was and your risk of getting a disease. Our advantage is giving you a current snapshot."

Chronix is developing a database of CNA signatures so that it can partner with diagnostics companies to develop tests to diagnose disease as well as prognostic tests to stage diseases such as cancer, helping to guide more effective treatment choices.

One of the three studies backing these claims will appear in next month's Clinical Chemistry. An editorial in the same issue gives some perspective on the breakthrough:

"It will probably still be a number of years before the diagnostic applications using massively parallel sequencing become commonplace . . . Currently, the equipment and reagents are still relatively expensive. Furthermore, the bioinformatic support that is needed to analyze the data is immense and out of reach for most diagnostic laboratories at the present time. Nonetheless, with additional technical advances and cost reduction in the coming years, it is highly likely that massively parallel sequencing approaches will eventually become a routine tool in laboratory medicine."

"We were one of the early adopters of the 454 mass sequencing machine, a protocol that can do about 400,000 sequences per six hours," Urnovitz said. "This breakthrough in massively parallel sequencing generates the data. We wrote the proprietary algorithms to analyze that data."

In one of the new studies, appearing in Clinical Chemistry, Chronix researchers applied the ultra-high speed sequencing technology and the company's algorithms to characterize and categorize the CNA markers present in multiple individuals. The resulting databases of CNAs associated with specific disease states can be used to identify people with undiagnosed diseases or to track changes in disease status. For example, the study found that one of the presumed healthy volunteers actually was infected with hepatitis B, confirming the utility of CNAs in finding unsuspected disease as well.

Another study, in Nucleic Acids Research, found that a blood test based on CNAs could identify the presence of bovine spongiform encephalopathy (BSE) and the related condition, chronic wasting disease (CWD), in live animals long before symptoms were evident.

"There is a public health urgency to test for BSE as a living test," Urnovitz said. "Currently you have to slaughter the cattle and go into the brain and look for microscopic lesions to determine if the cow has the disease or not. We can predict mad cow in cattle and chronic wasting in advance of clinical symptoms."

Following confirmation in larger studies, this new approach could change BSE testing, making it more affordable and possible to screen all cattle in the food chain before BSE symptoms appear.

The third reported study in Blood examined the use of CNAs in the management of cancer. Urnovitz and colleagues at the International Myeloma Foundation (North Hollywood, California) identified specific DNA sequences circulating in the blood of a patient with the bone marrow cancer multiple myeloma and tracked variations in the sequences as the patient's myeloma moved in and out of remission. They were surprised when CNAs also identified the development of a secondary cancer in the patient before it was clinically noticeable. This study in particular highlighted the potential use of CNAs in staging cancers.

"In my mind, the approach is to take the Internet of the body – the blood system. Looking at DNA and RNA, can we determine the Rosetta Stone to translate these sequences into messages of disease?" he asked rhetorically.

Urnovitz said the utility of Chronix's methodology is described in patent filings for multiple sclerosis, breast cancer and prostate cancer. But the potential for this technology is vast. It could have an impact on just about every chronic illness.

He said that studies related to multiple sclerosis and breast cancer will be published soon.

"The data is remarkable," Urnovitz said. "We can pick up, months to years in advance, a lesion so tiny in the base of the brain (related to BSE). The fact that we pick that up gives us a great feeling that the data will be supported by a proof of concept study."

Chronix is a 10-person company that has produced these scientific revelations with $20 million from venture backers over the last decade. Urnovitz said it's unlikely the company will expand. With proof-of-concept work done, it is turning to confirmatory studies.

"We're a discovery company," he said. "We file intellectual property and we will not be in manufacturing, marketing or sales. Our strength is the proprietary databases. We're now actively looking for partners in mad cow, breast cancer, multiple sclerosis and wasting disease."

He envisions multiple licensing deals, but added: "Our exit scenario is most likely an acquisition."

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