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MitoMics:

the next generation of molecular testing

In the world of early disease detection, Mitomics Inc. is pioneering the next generation of molecular testing. The Thunder Bay-based company is charting new territory with an innovative approach to the screening and diagnosis of cancer by using mitochondrial DNA (mtDNA) based biomarkers instead of traditional nuclear DNA-based biomarkers.

Its Prostate Core Mitomic TestTM (PCMTTM), released in 2011 for the more accurate detection of prostate cancer, has attracted much industry attention for its unique approach to detecting disease using its patented Mitomic TechnologyTM .

“We have a technology that we know can compete head-to-head with any other evolving or developing next-generation diagnostic technology,” says Robert Poulter, CEO and president of Mitomics. “But what makes us unique is the mitochondrial DNA, the significant early detection component, and our ability to pick a disease, go off and discover.”

Poulter, a Thunder Bay native with a background in banking and finance, joined the company in 2007, using his experience to take Mitomics’ PCMT from research and development to market. The company itself was founded in 2001 under the name Genesis Genomics, later becoming Mitomics – a blending of the words mitochondria and genomics.

Mitomic technology is what sets the company apart from others. It focuses on large-scale deletions in mitochondrial DNA, which can indicate cellular changes that can be associated with cancer development.

“The mitochondria have their own unique DNA,” says Poulter. “It’s a circular loop, and it’s very, very small but easy to monitor for alterations. We are able to determine where pieces, or sequences, of that DNA effectively go missing when disease hits. We can tell you what DNA sequence goes missing depending on what type of disease.”

That’s opposed to looking at the nuclear DNA, which has the ability to repair itself and fix the damage to the cell, until it is overwhelmed and has no choice but to change into a diseased cell. The mitochondria have no ability to repair themselves.

The idea to look at mtDNA deletions came from the company’s co-founders: a group of scientists primarily out of Lakehead University, including Mitomics’ CSO Ryan Parr.

With a PhD in biological (molecular)

anthropology from the University of Utah, Parr was at Lakehead working on analyzing and sequencing mtDNA extracted from the skeletal remains of ancient Egyptian populations. In the late 1990s, Parr and the other researchers came across a paper from Johns Hopkins that talked about using mtDNA as a detector for different types of cancer because of its fast mutation rate.

“We thought, ‘Wow, we work really hard on ancient mtDNA, this sounds like a good idea for us’,” says Parr. “That was actually the genesis of Genesis Genomics, the idea that you could use mitochondrial DNA to detect disease, and since we had worked with it, we felt like we may have an advantage in setting up a company to do early cancer detection.”

Their first target was prostate cancer, as they felt there was an unmet need in that area for better screening, diagnostic and treatment methods. Parr set to work

researching and developing mtDNA-based biomarkers, and one of the company’s first milestones was the results from a study meant to determine if they could find prostate cancer just by looking at mutations or alterations in the mtDNA.

“I remember very distinctly that we looked at the mtDNA from the prostates of individuals who had prostate cancer, and who’d had their prostates removed for that issue, compared to individuals who didn’t have prostate cancer,” says Parr. “We found there was quite a dif-

“Our test takes that same negative tissue, and analyzes it for this unique large-scale deletion of the mtDNA. If we can detect the deletion event or determine whether this piece has gone missing, we can tell the physician, ‘That tumour is in that prostate and you’ve missed it in your biopsy process. Go back in and find it, diagnose this patient.”

— Robert Poulter

ference between those who did and those who didn’t have prostate cancer. Moreover, we found that if you have a cancer lesion in your prostate, you will have the same mtDNA mutations in tissue that looks normal but is some distance from that tumour.”

At fi rst, the results were a puzzle to Parr: “I remember going back into the lab at night thinking ‘What have I done?’ Because the results aren’t correct, I should see differences between the tumour and the tissue

that looks normal.”

The answer, Parr soon found, lay in the tumour fi eld effect, fi rst devised in the 1940s by D.P. Slaughter and a group of researchers, and published in a 1953 study. The tumour fi eld effect occurs when the presence of a tumour affects all of the surrounding tissue. While this doesn’t necessarily mean that tissue will become malignant, it does not mean that tissue is excluded from becoming malignant either. There is a molecular potential for surrounding tissue to become malignant.

For Parr’s study to have revealed this effect was signifi cant, especially for the detection of prostate cancer.

“This fi eld effect extends the range of the sampling error of the core itself, so you can actually detect the presence of a tumour even by sampling histologically normal tissue,” says Parr.

The group published their work in 2006 on how mitochondrial DNA mutations showed the cancerization fi eld effect. After years of hard work and dedication, the next milestone was discovering that this fi eld effect could be monitored with a simple assay by looking at large-scale deletion. This led to the company’s central product, PCMT, and its commercialization in 2011.

PCMT gives Mitomics a leading edge in the detection of prostate cancer. Men suspected of having prostate cancer will undergo a prostate biopsy, recommended for those with elevated PSA (Prostate-Specifi c Antigen) blood test scores. In a prostate biopsy, a physician typically uses 12 needles to investigate the prostate which is approximately the size of a walnut. If the needles miss the tumour, a patient receives a false negative and can be called back for a second or third biopsy, an incredibly painful procedure that also carries risk of serious infection.

Poulter explains further: “Our test takes that same negative tissue, and analyzes it for this unique large-scale deletion of the mtDNA. If we can detect the deletion event or determine whether this piece has gone missing, we can tell the physician, ‘That tumour is in that prostate and you’ve missed it in your biopsy process. Go back in and fi nd it, diagnose this patient.’ ”

Because PCMT has a negative predictive value of 92 per cent, and a sensitivity of 85 per cent, one of the most signifi cant advantages of the assay, says Poulter, is its ability to clear up false negatives.

“If you had cancer, would you want to know?” says Poulter. “Absolutely. The earlier you detect cancer, the higher you’re ability to treat the disease and to survive. The problem here is in prostate cancer – it’s a disease that goes undetected for many years and it’s not because the physician is doing anything wrong, in fact the physician is doing everything right, but they just can’t pinpoint or locate the tumour.”

With PCMT, physicians can order a test on the existing prostate tissue samples. There is no need for a second biopsy.

Currently, the samples are analyzed out of the company’s CLIA-certifi ed commercial laboratory in Aurora, Colorado. While its commercial lab is located in the U.S., Mitomics remains headquartered out of Thunder Bay, the location of its head offi ce, R&D and fi nancial operations. In a recent develop-

“We found there was quite a difference between those who did and those who didn’t have prostate cancer. Moreover, we found that if you have a cancer lesion in your prostate, you will have the same mtDNA mutations in tissue that looks normal but is some distance from that tumour.”

— Ryan Parr

ment, Mitomics announced an agreement with U.S.-based LabCorp, where urologists will be able to order PCMT through DIANON Systems Inc. It is the fourth such U.S. distribution agreement inked for PCMT, and Mitomics has also forged agreements with distributors in Canada, the UK, Ireland, Germany, Australia and New Zealand.

Along with further marketing of PCMT, Mitomics is pushing toward the future with an active R&D program based on its mtDNA platform. The company aims to develop a urine test for screening prostate cancer, which holds the promise of potentially replacing PSA testing. Also in the pipeline are a number of other mtDNA tests for early detection of a variety of diseases including: breast cancer, uterine cancer, cervical cancer, colorectal cancer, endometriosis, melanoma, skin cancer and other dermatological conditions. Parr is convinced that the answer to early disease detection may well lie with the mitochondrial genome.

“Research has always concentrated on the nuclear genomes, but what we’re starting to fi nd out is that the mitochondria are the nexus of many biochemical reactions,” says Parr. “The mitochondria may really be the master of the orchestra. The whole story is not written in the nuclear library.”

For Poulter, this potential puts Mitomics’ biomarkers at the forefront of personalized diagnosis and treatment: “Our technology just fi ts perfectly in the pharmaceutical world. The buzz word today is personalized medicine. Our platform is exactly that. It’s being able to personalize the identifi cation of disease, and then marry that up with the appropriate treatment for that disease. And that’s what our technology is targeted to do.” The future is bright for Mitomics.

To see this story online visit http://biotechnologyfocus. ca/?p=2207