Parkinson鈥檚 Disease (PD) affects nearly 100,000 Canadians and 10 million people worldwide. Characterized by a dopamine deficiency in the brain, this neurodegenerative disease disrupts signal transmission in the brain, impacting its proper functioning. Motor symptoms, like tremors, slowness of movement and imbalance problems can appear and deteriorate in patients who have quietly carried the disease for years. Equally devastating are PD鈥檚 lesser-known symptoms, like depression, anxiety, hallucinations, dizziness and sleep disorders.
While there is currently no cure for PD, a team of researchers at the Neuro (Montreal Neurological Institute-Hospital) has been advancing PD research through groundbreaking innovation. Led by Thomas Durcan, Associate Professor in the Department of Neurology and Neurosurgery at 黑料不打烊 and Director of the Neuro鈥檚 Early Drug Discovery Unit, the team has applied stem cell technology to create human organoids.
Organoids are minuscule, three-dimensional tissue cultures derived from stem cells that mirror key features of human organs. With the help of Dr. Edward Fon, Scientific Director of the Neuro, Durcan鈥檚 team has successfully recreated the most complex organ of all: the brain.
Image by Emilie Hackett.
Brain organoids are minuscule 3D human cell cultures that mirror key features of the human brain. Here, Research Assistant Paula L茅pine showcases a brain organoid culture that she personally cultivated.
Serving as the closest available model to patients鈥� brains, organoids provide a highly precise and innovative approach to studying disease mechanisms and accelerating drug discovery.Brain organoids are an exciting development in neurological research, as they can be personalized using reprogrammed cells from patients.听Serving as the closest available model to patients鈥� brains, organoids provide a highly precise and innovative approach to studying disease mechanisms and accelerating drug discovery.
However, developing these two-millimetre-wide organoids at scale has proven to be challenging.
鈥淭he methodology was inconsistent. The organoids varied in size and shape, making it difficult to ensure their health and reproducibility,鈥� explained Durcan. 鈥淲e wondered if we could standardize the process and scale up production while also reducing the time-consuming and physically taxing workload in the lab. We needed a better system.鈥�
With support from听,听HBHL听补苍诲听NeuroSphere, Durcan鈥檚 team collaborated with Christopher Moraes, Associate Professor in the Department of Chemical Engineering, to scale up the organoid production process for testing potential therapeutics.
By growing the organoids on biofabricated disks and incubating them in large bioreactors, the team can now control and standardize brain organoid growth, generating over 800 organoids at once. This streamlined approach not only cuts costs and saves time but also facilitates the production of patient-specific organoids, improving the potential for personalized treatments in variable diseases like PD.
鈥淧arkinson鈥檚 isn鈥檛 determined by one gene. It鈥檚 basically an umbrella term鈥攖here are over 100 genes to Parkinson鈥檚,鈥� explained Durcan. 鈥淥ur goal is to explore these different genes with advanced imaging tools and expanding into an automated 3D imaging platform. We started with a biology problem that became an engineering problem and is now becoming a data problem. With countless terabytes of data from 3D imaging these organoids, the next frontier will be applying artificial intelligence towards reconciling all the data and identifying disease signatures.鈥�
The COVID-19 pandemic is partially to blame for this advancement, as limited lab access in March 2020 presented the team with a difficult decision. Nguyen-Vi Mohamed, a postdoctoral fellow at the time, first pitched the idea of combining the biofabricated disk and bioreactor technologies.
Research Assistant Paula L茅pine describes this as a significant leap of faith: 鈥淥ur old method of production involved feeding the organoids at least three times a week. We had to reorganize everything. We transferred all the organoids in large bioreactors that could contain hundreds. Either we took a chance, or we lost them all,鈥� she said.听
As a result, the team鈥檚 research was unexpectedly accelerated. 鈥淲e scientists like to take our time and look at all the variables,鈥� admitted Durcan.鈥淏ut we were forced to test our theory and hope for the best. The culture stayed alive, and we were able to use them in the fall of 2020. We鈥檝e continued with this process ever since.鈥�
The open science approach adopted by Durcan鈥檚 team ensures transparency and accessibility for the broader scientific community: their methodology is available online in multiple languages and formats. 鈥淥ur goal was to build and improve these processes and workflows, applying them into a real translational discovery pipeline. We鈥檙e currently building a portal with the data on the cell lines and the modules,鈥� he noted.
As this new technology gains traction, collaborative efforts in knowledge translation are crucial for progress in PD research. 鈥淭he scientific community is coming to accept that organoids can be used beyond neurodevelopmental studies: they are a useful model for neurodegenerative diseases,鈥� remarked L茅pine.
A testament to the potential of brain organoids, Durcan鈥檚 team is now working with听. This open science partnership allows the team to leverage and distribute data collected from the organoids.
鈥淲e contribute insights that propel the research forward in the knowledge translation pipeline. These synergies allow our partners to conduct additional testing and research of therapies,鈥� said Durcan. This collaborative effort is poised to accelerate the discovery process for PD and foster a dynamic ecosystem for breakthroughs and innovations in the field.
Image by Emilie Hackett.
From left to right: Research Assistants Mar铆a Bel茅n Baeza Trallero and Paula L茅pine and Research Associate Cecilia Rocha. Trallero, L茅pine and Rocha are integral members of the team dedicated to advancing brain organoid technology.
