We should all be thankful for the advances of modern medicine, particularly over the last decades. Cancer, for example, once considered a death sentence, is steadily being beaten back. Since 1991 mortality rates from this disease have declined by 33% in the US. Much of this improvement is due to the development of new drugs.
Unfortunately, the same is not true for neurodegenerative diseases. Illnesses such as Alzheimer’s or Parkinson’s disease primarily affect the brain and nervous system. And while many millions have been invested in research, precious little has come forward in terms of effective therapies.
Amyotrophic Lateral Sclerosis (ALS), for example, is an illness that progressively affects patients, and normally causes death in as little as four years after diagnosis. But since 1995, only three new drugs have been approved to treat the disease – and none of them are a cure.
Drug discovery: a difficult challenge
Why is it so hard to find a cure for this and other similar diseases? Developing new medicines is a long and expensive process. Only one in 1,000 of drugs that enter pre-clinical trials will succeed to be tested on humans, and only one in five of those that enter in-human trials are finally approved. That is a success rate of only 0.02%.
Moreover, in the case of neurodegenerative disease, studying nerve cells themselves is a fraught exercise. Keeping them alive in cell culture long enough to study an age-related neurodegenerative process has been an issue for decades. Until now that is. The story begins when post-doctoral fellow Laila Al-Alwan and Jean-Pierre Clement, a graduate student working toward his M.Sc. in the Integrated Program in Neuroscience at McGill, made a serendipitous discovery.
“We were looking at something completely different, we were looking at coatings to enhance the biocompatibility of electrodes going into the brain,” Clement explained.
He found that neurons particularly liked a coating called dendritic polyglycerol amine, or dPGA, for short. Neurons that came into contact with a microbead coated with dPGA would form a connection to this synthetic surface. He decided to further explore the properties of this coating.
“We figured if they love it so much as a coating on a tiny bead, what happens if you put the neurons and grow them directly on top of this coating? So, we dropped neurons on surfaces with this new coating and lo and behold, it worked! The neurons grew, and they grew really, really well,” he said.
Issues with Traditional Coatings
The discovery was significant because dPGA enabled adhesive cells (i.e., neurons) to live longer in the lab than previously possible. Typically, researchers will use synthetic proteins, such as poly-lysine, to coat a surface to grow cells on. While these synthetics provide an adequate base for growth, the cells seldom last long.
“As the cells are growing, they start to secrete proteases that break down proteins, so the cells just start chewing up the substrate. Because of this, it is very hard to keep neurons alive in culture for longer than a few weeks,” described Professor Tim Kennedy of the department of Neurology and Neurosurgery, who was Clement’s supervisor.
Kennedy and Clement found that dGPA allowed adherent cells to live longer in culture. The discovery of dGPA as a coating is significant as it will enable scientists to provide a solid foundation for long-term cell culture and experiments on mature neurons.
“By having a solid foundation in the culture, and then having the cells mature this allows you to do experiments that in the past, you just couldn’t do because the cultures didn’t last that long. Now, you can actually think about doing experiments with more mature neurons,” said Kennedy. A game changer in other words.
Enter the MIF
It wasn’t long after this discovery that Clement and Kennedy realized this was something worth taking further. Together, they applied to the McGill Innovation Fund (MIF), first in 2021 (where they received Develop level funding of $50,000), and again the following year where they earned the highest level of funding available, the Deploy stage of $100,000. Soon after the Deploy award, they founded a company for the technology called DendroTEK Biosciences.
The MIF is more than just an award competition – it provides comprehensive support to teams. “I’m very impressed with the resources provided by the MIF. They regularly organized events like lunch and learns, gathering various high caliber presenters that you can turn to and ask questions on all sorts of subjects related to commercialization,” said Kennedy.
“I already had experience managing Tim’s lab on a daily basis which is how I started working with them. Transposing my skills into the business aspect was definitely a challenge. I’m knowledgeable but I am also learning on the spot, but with the MIF we are really well surrounded so there is always someone we can turn to ask a question, and that is essential because we’re not businesspeople,” said Marcal.
“This startup became possible due to a long-term collaboration between my lab at McGill and Professor Rainer Haag’s lab at Freie University in Berlin. This has recently grown to become part of an international NSERC CREATE grant that is supporting exciting new interactions between chemists and neuroscientists at McGill, Freie University and UBC,” remarked Dr Kennedy.
Early sales point to future impact
dPGA has transformative potential for drug discovery, especially for neurodegenerative diseases. “The neurons in your head are fundamentally, mature cells. They've been with you your whole life. So you want to try and model that in cell culture,” explained Dr Kennedy.
“For motor neurons that are needed to grow to study ALS, if you are lucky, they might live up to four weeks. We have been able to keep them for three months, and that’s major in terms of the differences it enables to model diseases,” added Clement.
Pharmaceutical companies have taken notice and have started buying dPGA for their labs. “Our dPGA coating is now being used by big pharmaceutical companies to grow their cells in culture for large drug screenings for different types of diseases. So anything from ALS to Parkinson’s to Alzheimer’s, our coating is being used to discover the drugs of tomorrow,” said Clement, who now bears another title: DendroTEK CEO.
