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Dr. David Vocadlo Talks Carbohydrates, Alzheimer’s, and Entrepreneurship

By April 12, 2017October 6th, 2023No Comments

Dr. David Vocadlo is a Canada Research Chair and professor in the Department of Chemistry at Simon Fraser University. In addition to his work at the university, Dr. Vocadlo is also the CSO of Alectos Therapeutics, a pharmaceutical company he co-founded based on an idea inspired by his academic research. We sat down with Dr. Vocadlo to discuss his journey starting up the company while maintaining a rigorous research program.

What is the central focus of your research program at Simon Fraser University?

We focus on the role of carbohydrates in human health and disease. Fundamentally we’re interested in this because every single cell from every kingdom of life is coated in carbohydrates. But we still don’t know the function of most of these carbohydrate structures. One of the problems in the field has been that there haven’t been sufficient research tools that have been exploited to uncover the molecular roles of these unusual and complicated structures. A major focus in our lab is developing chemical and biochemical tools that we can then exploit to understand the functions of some of these intriguing structures.

Specifically, one of our major projects over the past years has been to investigate an unusual modification of proteins that is not well understood. Most people think of glycoproteins on the cell surface, but this modification is different in that it’s found on thousands of different proteins on the inside of the cell. It’s a single sugar unit known as O-GlcNAc that’s O-linked onto serine and threonine residues. We’ve been studying this sugar by exploiting new tools and collaborating with researchers around the world to try to improve our understanding of what it is doing.

Have you always been interested in studying carbohydrates?

Absolutely! I started off my graduate studies working under Dr. Steve Withers at the University of British Columbia on carbohydrate processing enzymes. So my formal training is in chemical synthesis of carbohydrates, biochemistry, and enzymology. Working with Steve was inspirational to me, as he’s just an outstanding scientist. I studied a range of different carbohydrate processing enzymes, and at the time I found it really interesting because not much was known about this family of enzymes.

I then did a postdoctoral fellowship down at Berkeley with Dr. Carolyn Bertozzi who is a dynamo. She is a chemical biologist studying the roles of carbohydrates, and developing some new tools to study these structures from a more cell biology perspective.  When I started my own lab, my objective was to combine the chemistry and enzymology that I learned during graduate school with some of the elements of cell biology and animal physiology that I learned during my postdoc in order to work on the roles of little understood carbohydrate structures in human health and disease.

You co-founded Alectos Therapeutics fairly early on in your career as a professor at SFU. What gave you the idea to branch out and start your own company?

When I established my lab, I started off studying the two enzymes that regulate O-GlcNAc – O-GlcNAcase (OGA) and O-GlcNAc transferase (OGT). One of the early projects we had was to develop tools that we could use in cells, as well as in vivo animal models, to antagonize both of these enzymes. At the time, the thinking in the field was that blocking the action of OGA would lead to diabetes. So we started out with the objective of using these tools to understand the temporal relationship between O-GlcNAc and the development of type 2 diabetes.

We succeeded quite early on in antagonizing OGA, and in 2008 we published a paper that described really potent inhibitors of this enzyme. This came as a bit of a surprise, because it had previously been thought in the field that antagonizing this particular enzyme would be deleterious. We allocated a lot of time to try to find a link between increasing O-GlcNAc using these antagonists of OGA and the development of diabetes, but we were never able to do so.

This stimulated us to think about what else O-GlcNAc might be beneficial for, and we realized we might be able to use them for therapeutic benefit. We decided to look at the role of O-GlcNAc in Alzheimer’s disease and the aggregation of a protein known as tau. Tau is a microtubule-associated protein, and one of the pathologies of Alzheimer’s disease are clumps of this protein within neurons. People with more tau aggregation generally have more advanced forms of Alzheimer’s. At the time there was a paper that showed that tau is modified with O-GlcNAc, but that in these clumps tau was not O-GlcNAc modified. We speculated that this sugar modification may prevent the aggregation of the protein by increasing its solubility and preventing it from packing together in these fibril-like structures. We then showed that treating mice with OGA antagonists over a period of months in a blinded study was in fact protective against tau and neurodegeneration.

So that was when we realized that there was potential to establish a company. I had a friend, Ernie McEachern, who did grad school at UBC, a postdoc at Stanford, and then was a group leader in chemistry at AnorMED. We had been talking for quite some time about potentially starting a company, and I thought this would be a great opportunity. I talked to Ernie about it and he agreed, so we co-founded Alectos based on this technology of OGA inhibitors – he heads the company as CEO and we still talk a lot of science.

What did Alectos do with this technology?

At Alectos we improved on the technology, and then we formed a partnership with Merck. Collaboratively Merck and Alectos have advanced the technology through preclinical studies, and now it’s actually gone into the clinic. It’s quite amazing. Merck and Alectos also developed PET imaging agents for OGAto be able to look at target engagement.

What has been the most challenging aspect of starting up a company?

The initial part of establishing the company, getting all the agreements in place, making sure the intellectual property is well laid out, and getting the right people together was incredibly time intensive. SFU offered support though, which is great. Then negotiating agreements with potential partners also took a really long time. Basically just the inevitable ups and downs of business and science. It’s a lot of science, so there’s always setbacks, and you have to work through them.

What advice would you give to an academic interested starting their own company?

My first piece of advice would be to try to do it with someone else. Find someone that you can work together with who is really an outstanding, trustworthy person. Also have a clear understanding of the goals. Make sure that the intellectual property is nailed down, and that you’re trying to develop something in an area where there is really a clear need. You also want to get good advice from people from various walks of life.

In Canada we have a lot of great science and all translation springs from the fundamental, which puts us in a good position. But I think ultimately in Canada what we need to do is develop a more entrepreneurial culture in biotech, and part of that is fostering that enthusiasm in young people. If you’re already primed for the possibility, then you can recognize a really good idea or potential technology the moment you come across it. It’s not that frequent that you come across something that really has tremendous potential, so when you do it’s great to be able to recognize it.

Thank you for taking the time to talk with us, Dr. Vocadlo! We look forward to continuing following both your academic and entrepreneurial efforts!