Innovative PCR tests are monitoring genetic diseases

Before the spring of 2020, there were few of us, outside the life science communities at least, who were familiar with the words “PCR test”.

A polymerase chain reaction (PCR) test, as we now know, finds the presence of a particular genetic material from a disease or virus, such as cancer or COVID-19, in a DNA sample.

It is one of a wide variety of assays and instruments used in the initial testing and subsequent monitoring of genetic diseases, including cancer.

But post the SARS outbreak in 2002-2004 and pre COVID-19 there was at least the beginnings of frustration among some biologists that existing PCR tests lacked sufficient sensitivity. And they were also too time consuming; it took two days to produce a result.

Searching for new health care solutions for new markets

“The problem is that you’re not just looking for a needle in a haystack, you’re looking for one particular needle in a haystack that contains a thousand others.” – Bech Christensen

The sensitivity and speed of existing PCR tests was a concern, particularly to Ulf Bech Christensen, the founder and CEO of Pentabase, then a small but established and well respected Danish life sciences company.

In the words of one of his clients, Bech Christensen has “the personality of a stereotypical viking explorer”, a man with a restless curiosity and an almost disarming directness. Not only a highly experienced research chemist, Bech Christensen is also a serial entrepreneur who studied business management in growth companies at INSEAD. Some might say his qualities are detectable in his own DNA.

Wherever Bech Christensen’s drive comes from, it is certainly no disadvantage when it comes to the relentless pursuit of an objective in life or life sciences. Such as achieving a radical break-through in PCR monitoring to be able to provide the best possible treatment to every single cancer patient, something which all starts with the best possible and individualised screening and diagnosis.

Whilst others pursued incremental improvements to existing methodologies, the Pentabase team chose instead to focus on more radical improvements, by focusing on the chemistry of nucleic acid, Bech Christensen’s field of specialisation. The result was a completely new form of qPCR for evaluation of epigenetic changes, that entirely eliminated the need for the time-consuming pre-treatment of the patient’s DNA sample. It is called direct analysis of DNA methylation (EpiDirect) and produces a result in two hours.

By eliminating the need to pre-treat the sample, the process allows fewer opportunities for error and therefore produces fewer false positive results. And as a qPCR test, it also enables real time monitoring of the advance or regression of a disease, resulting in more personal and more effective patient treatment and care.

Pentabase now offers a suite of five platforms and products, such as qPCR probes and assays for detecting somatic mutations and methylation in DNA to other IV companies and end-users like hospitals and laboratories, under the name EpiDirect, not just expanding the market but (in Bech Christensen’s own words), “creating a new market”. And not only in the monitoring of COVID-19, but in the monitoring of all genetic diseases both long established, such as cancer, and those that have come to attention more recently, such as Mpox. It also allows earlier and easier detection of age-related diseases such as Alzheimer's disease and diabetes.

Collaborative projects for COVID-19 testing

“I think Pentabase can take some pride in the contribution we made to society’s response to COVID-19.” – Bech Christensen

As the demand for rapid and reliable monitoring of the COVID-19 Virus at scale became an urgent global necessity Pentabase grew rapidly from a team of just 12 to 220. “The only reason that our growth at that rate was possible” Bech Christensen says, “was my complete trust in the judgement of those first 12 colleagues.”

Bech Christensen’s previous experience in biotech in Australia also served him well in alerting him to the origins of the virus in Asia Pacific and its rapid spread. By the time the virus became established in Europe, Pentabase was ahead of the curve and already in a position to be able to quickly come to the aid of the continent's initially faltering response. And, crucially, he was able to source the necessary chemical reagents.

He recalls those days with a mixture of pride and some regret. He and his team contributed hugely, but found unnecessary obstacles in their way. He was, and remains to be, highly critical of public authorities’ initial reluctance to fully engage with private sector SMEs and niche players.

“We were working 24/7”, he recalls. “I lived in the office, grabbing a couple of hours sleep here and there when I could while the team worked in two shifts, each updating the other on progress every twelve hours.”

Their dedication was tireless, and despite (or perhaps because of) Bech Christensen’s early and vocal criticisms, Pentabase formed collaborative projects with other companies to ramp up testing capacity across the Danish health care system.

They were then able to offer specialist services to companies who urgently needed to reopen and resume business. For example, professional sports teams, including the Danish Olympics team, were able to return to training and travelling, and Frankfurt airport could reopen ahead of schedule thanks to Pentabase’s collaboration with a German company that provided sufficiently sensitive testing for identifying emerging variants of concern.

International collaboration and human chemistry

“By far the most productive and most enjoyable collaboration we have had came as a result of Eurostars.” – Bech Christensen

Two words that occur frequently in conversation with Bech Christensen are “investment” and “collaboration”. Both have become increasingly interdependent and key to Pentabase’s success.

It was Pentabase’s first of several successful applications to the Eurostars funding programme that led to an introduction to Milo Frattini and his team at the Istituto Cantonale di Patologia EOC.

Bech Christensen singles out Dr. Frattini and his team as invaluable collaborators for conducting the clinical trials essential to bringing EpiDirect to market. They not only share a common culture, Bech Christensen says, but both are completely aligned on Pentabase’s four non-negotiable values of care, adaptability, scientific excellence and accountability.

Perhaps these qualities are detectable in Frattini’s DNA also.

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