From Bench to Bedside: Seamless Collaboration Through TDRA
Spotlight on: Drs. Graham Collingridge & Tarek Rajji
Although we each share 99% of our DNA with other humans, every person’s brain is different, and every disease manifestation is unique. Increasingly, a personalized approach to diagnosis and care is considered both optimal and doable. This requires a deep understanding of the underlying mechanisms of brain diseases.
The basic science work required for these discoveries involves significant trial and error work, and observations of brain tissue at a microscopic level. Unlike other parts of our body, human brains cannot be biopsied. The role of pre-clinical models in brain research is therefore critical.
The close interaction between researchers working on pre-clinical models (bench) and those designing updated clinical protocols (bedside) is essential to delivering personalized care in brain medicine.
Brain cells, or neurons, are the information messengers for the brain, spinal cord and entire body. They use electrical and chemical signals to send data between different areas of the brain and body. When anything goes wrong with these intricate processes – either through disease or injury - the impact can usually be observed through a collection of symptoms, which affect functions within the body. To help regain functionality that is lost, the brain needs to adapt or ‘rewire’ itself. This is called brain plasticity (or neuroplasticity).
Long-term potentiation (LTP) is a long lasting increase in transmission between different neurons, which is achieved through electrical stimulation in different pathways. LTP can be effectively stimulated using clinical-grade technologies. This treatment can make the neural pathways stronger and better able to do their jobs (for example storing memories). Click here for more on this process.
“The molecular basis of LTP is the most complex machine in the known universe. It has thousands of components, where an error in one component can lead to a devastating consequence; for example early developmental disorders such as schizophrenia or autism, or diseases that typically manifest later, like neurodegenerative diseases that can lead to dementia,” said TDRA researcher Dr. Graham Collingridge.
Dr. Collingridge goes on to say that scientists around the world are interested in understanding the process of LTP better, so they can correct errors that show up uniquely in different people and in different brain diseases.
Understanding LTP is critical to neurostimulation, where a stimulus is applied to an area of the brain or nervous system, often to treat a disease. Neurostimulation can be less invasive and carry fewer side effects than pharmaceutical solutions. In treating symptoms of cognitive decline or dementia, neurostimulation can be utilized to support cognitive counter-balancing mechanisms – which can help the body to better cope with the effect of aging processes on the brain, and promote brain plasticity.
Dr. Tarek Rajji and colleagues are utilizing different forms of neurostimulation to treat dementia and depression symptoms, for example, in both clinical practice and research studies. Many of today’s approved clinical protocols are based on work done in pre-clinical models decades ago. While work done at the “bench” has progressed, clinical protocols require updating, and this is where the research comes in.
The ‘Bell Let's Talk/Brain Canada’ funded INPiRE-D study, led by Dr. Rajji, working closely with Dr. Collingridge and Dr. Evelyn Lamb’s labs, is one example of close collaboration driving real innovation. This work is focused on advancing research on enhancing theta burst stimulation for depression.
“Designing a translational project that will bridge, within the span of three years, new discoveries in the basic science labs to advance clinical therapies for people with depression is a highly promising approach in the quest of these new treatments”, said Dr. Rajji.
It is only through this close collaboration from bench to bedside that true innovation will be achieved.