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By blocking an errant enzyme, Drpitor1a could fight cancer, Alzheimer’s, and pulmonary hypertension.

researchers have gained recognition for the discoveries they have made in medicine, engineering, and the sciences; innovations that have improved the lives of people around the world. To make sure that the university and the public continue to benefit from this work, Queen’s Partnerships and Innovation (QPI) promotes the discoveries of university researchers who have assigned their intellectual property to Queen’s and whose work is ready for licensing and commercial application. QPI leads the commercialization processes, including the protection of the intellectual property, the creation of strategies to further its development, the search for funders, partners, and licensees, the negotiation of terms, the management of relationships, the collection of licensing and royalty revenues, and their disbursement to inventors.

“This stuff works."

The “stuff” that Professor Stephen Archer refers to is a compound that he and his colleagues, Dr. Danchen Wu and Dr. Michael Wells, have developed called Drpitor1a. An enzyme inhibitor, early research suggests that it may be very effective in fighting Alzheimer’s disease, pulmonary hypertension, and breast and other cancers. The challenge for Archer and Queen’s Partnerships and Innovation (QPI) is to find a partner with the skills or the financial means to take it to the next level.

Mitochondria are called the power plants of our cells, the producer of the energy that our bodies need. That’s not their only function, however. Mitochondria are typically found in a network, but this network can break down in a process called fission. Through fission they regulate cell replication, remove unnecessary or dysfunctional cell components, and participate in the removal of damaged or unwanted cells (a process called apoptosis). They do this primarily through an enzyme known as dynamin-related protein 1 (DRP-1).

In certain diseases, the production and action of DRP-1 is increased, with varying effects. In what are known as hyperproliferative diseases, such as cancer or pulmonary hypertension, the production of DRP-1 leads to greatly increased cell growth. For example, in pulmonary embolism, the blood vessels in the lungs begin to close because of proliferating cells, forcing the heart to pump harder and harder. Paradoxically, in some neuro-degenerative diseases, such as Alzheimer’s, where mitochondrial fission is increased thanks to DRP-1, it leads to cell death, not proliferation. Controlling the action of DRP-1 would help fight these diseases.

The story begins back in 2017, when Dr. Wells, in his role to commercialize intellectual property developed by Queen’s researchers, was working with the late Dr. Victor Snieckus at Queen’s. “He had a library of synthetic compounds that we were trying to sell to industry,” says Dr. Wells, who was screening these 4,000+ compounds to see which ones might interact with biological targets. “I was doing this for this for a lot of different researchers. I did this for Dr. Archer, and I thought there might be something there.”

“We did a lot of screening,” confirms Dr. Archer, trying to discover which of these compounds managed to block the operations of DRP-1 on the cells. “And we found that one, Drpitor 1, worked.”

From this they have been able to develop Drpitor1a, which their U.S. patent describes as a “novel, specific” DRP-1 inhibitor. Fifty times more potent than Mdivi-1, previously the best DRP-1 inhibitor available, Drpitor1a has proven effective and safe in the treatment of rodent models of lung cancer, ventricular damage, and pulmonary hypertension. Another independent research group has verified its effectiveness in cancer treatment. These days, as well as working on his own additional research, Archer responds to requests from researchers around the world who have heard about what he’s done and want samples to see if what he and his co-inventors have developed really is effective. “We give it away, and we find it does what we say it does, which is really encouraging.”

For all its promise, however, Drpitor1a is still in its early stages. A Partnerships Development Officer with the QPI team, Dr. Wells says, “part of my job is to try to sell IP developed at Queen’s to biopharmaceutical companies or license it to companies that have the financial wherewithal and the technical expertise to develop it as an actual product.” With Drpitor1a, there are currently a couple of obstacles to this. For one, the test on rats and mice aside, it is still at the pre-clinical stage. More work will have to be done. For another, the patent they hold, says Wells, covers method, not composition of matter, which “is really important in the biochemical industry because that compound is literally your actual product.” It is not unheard-of for a company to bring a product to market based on a method patent, but it is significantly more challenging.

These obstacles, and the generally risk-averse nature of the industry aside (“the biggest lesson that we’ve learned,” says Dr. Archer, “is that drug companies look at things very differently than academics”), there is already interest in Drpitor1a, particularly in the field of Alzheimer’s treatment.

“Alzheimer’s Research UK were interested, but they needed to get two commercial partners to commercialize our research and they could only get one.” Through QPI, says Dr. Archer, they are also talking to a couple of companies who might be interested in pursuing Drpitor1a’s development as a treatment for Alzheimer’s. As Archer points out, it doesn’t have to be an Alzheimer’s drug. “I am kind of agnostic about this,” he says. “It’s a drug that blocks an enzyme and whenever an enzyme’s turned on inappropriately, the drug might be beneficial.”

Going forward, Dr. Wells says, “We could apply for grants and use that to hire a synthetic chemist and it becomes a standard drug discovery program.” One requiring a large amount of money and expertise, the kind usually found in a biopharmaceutical company. Another possibility is partnering with a company such as adMARE BioInnovations, which he says, has “an interesting process where, if they like a technology, they’ll work with the investigator, they’ll put money into a research program to expand the chemistry, and work with Queen’s to file the intellectual property, so they might be a really good partner in this process.” Getting Drpitor1a out there, he says, “will be tricky, but it’s really just a question of money.”

Readers interested in licensing or learning more about the technology Dr. Archer has developed, should contact Michael Wells at michael.wells@queensu.ca.