New drug could prevent leading cause of death in young athletes

Also, pioneering system for wound closures shortens time by up to 80 per cent and reduces the risk of infection and scarring

Pictured (l-r) are co-founders of EpiCor Therapeutics, a UCD School of  Medicine start-up: Dr Chris Watson, Dr Nadia Glezeva and Dr John Baugh,  overall winner of the 2016 UCD VentureLaunch Accelerator Programme
Pictured (l-r) are co-founders of EpiCor Therapeutics, a UCD School of Medicine start-up: Dr Chris Watson, Dr Nadia Glezeva and Dr John Baugh, overall winner of the 2016 UCD VentureLaunch Accelerator Programme

The development of a drug to treat devastating heart disease and a revolutionary system that cuts wound closure time after surgery by 80 per cent are two of the projects that graduated from the recent VentureLaunch Accelerator at UCD’s Nova innovation hub.

Hypertrophic obstructive cardiomyopathy (HOCM) is hardly a household name. But those with children involved in sport might be more familiar with it than they think. HOCM is a leading cause of death in young athletes.

With HOCM a portion of the heart muscle becomes enlarged and this can lead to heart failure. The disease is a major cause of sudden cardiac death in individuals of all ages and there is currently no drug available to treat it. As of now the only way to deal with HOCM is by invasive surgery and this has limited success.

EpiCor Therapeutics is a spin-out from the UCD School of Medicine, which has set itself the task of finding a successful treatment for HOCM. "There are no approved drugs that block or reverse cardiac hypertrophy," explains associate professor of medicine, John Baugh, who co-founded the start-up with co-principal investigator, Chris Watson, Nadia Glezeva, Chris Watson, Mark Ledwidge and consultant cardiologist Prof Ken McDonald of St Vincent's Hospital.

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“There are several drugs that can relieve the symptoms but none that can reduce the growth of the heart. In cases of severe hypertrophy the only options are surgery or injections of alcohol to kill cardiac muscle cells. We believe our drug has the potential to both prevent and reverse cardiac hypertrophy.”

The EpiCor project (which won UCD’s Start-Up of the Year Award in 2016) began a decade ago with the overall aim of developing treatments for heart failure. The promoters are planning a portfolio of products and repurposing the drug 5-azacytidine to treat HOCM is their first.

“We have been studying the biological mechanisms that drive cardiac hypertrophy and believe that the regulation of gene expression, via the process of DNA methylation, plays an important role,” Baugh says. “We have elucidated pathways that drive DNA methylation in cardiac cells and based upon this work have developed the hypothesis that blocking DNA methylation might have therapeutic benefits. The drug we are repurposing is known to inhibit DNA methylation and we have shown that it can reduce the growth of cardiac cells.”

EpiCor’s product has global appeal not least because of the cost of treating HOCM and hypertrophic heart disease. Baugh says the associated healthcare costs of treating HOCM in the US alone are over $1 billion (€0.93bn) a year.

So far around €550,000 has been invested in EpiCor with the lion's share of the funding coming from Enterprise Ireland's commercialisation fund. The next step is to seek regulatory approval to proceed to clinical trials. Decisions will also have to be made about the best route to market. Baugh says a partnership or licensing agreement is most likely. He is also hopeful that Celgene, the current producer of 5-azacytidine, may see the potential in a new application for its drug.

Good timing plays its part in business success and EpiCor appears to have got it just right. Interest in so-called “orphan (rare) diseases” is growing thanks to more attractive financial incentives. Traditionally, large pharma companies have not taken much interest in finding cures for uncommon conditions.

The overall aim of the VentureLaunch Accelerator Programme is to fast track new ventures based on intellectual property emerging from UCD. "The programme equips our academic researchers with the commercial pieces they are going to need to interact with their respective markets in a meaningful and practical way," says the programme's manager, Cody Mayoh. "These ventures are propelled into our incubator at NovaUCD where they get the support to grow into companies with global market potential. In the past three years alone our spin-in and spin-out companies have collectively raised over €100m in equity investment."

Latch Medical took part in VentureLaunch to accelerate the development of its pioneering system for post-operative wound closure. Its collaborators are Seamus Morris, consultant orthopaedic surgeon and director of the National Spinal Injuries Unit at the Mater Hospital, medical devices expert Nicky Bertollo and Eoin O'Cearbhaill, assistant professor in Bioengineering at UCD.

“The main techniques used for wound closure have been the same for a very long time and are sutures, staples or glues,” Morris explains. “Skin sutures are time consuming to deploy. Skin staples are faster but cause scarring. Skin glues are typically used for smaller wounds and are less robust. Our revolutionary mechanical tissue anchor system offers a unique combination of rapid, robust and atraumatic wound closure.”

Called The Latch, the system shortens wound closure time by up to 80 per cent and reduces the risk of infection and scarring in the process. “It takes an average surgeon a minute to close 1-2cm with wound closure for major cases taking up to 30-40 minutes,” Morris says. “The initial inspiration for the tissue anchor system came from nature and looking at the mechanisms animals and insects use to penetrate and latch onto the tissue of their prey.”

The Latch is a series of tiny discs with a hole through the centre. They are inserted before surgery along both sides of the proposed incision. When the time comes to close the wound the surgeon uses a nylon thread to “lace up” the wound in a similar fashion to lacing a shoe. The big advantage of the system is that it is placed in the superficial layer of the skin thereby making the closing less invasive while the nerve endings that produce pain are not involved. Its positioning also makes it easy to remove. The Latch will work in a wide range of surgical settings and can be automated making it possible for practitioners others than surgeons to use it in emergency or military settings for example.

Morris estimates that the closures market is worth around $6 billion (€5.6bn) a year and he hopes The Latch will be on sale by 2018. The project has been funded by a commercialisation grant of €500,000 from Enterprise Ireland and the company is now looking to raise further funding to complete the commercialisation process.