Research plan of the first three Brain Repair Program teams (2004-2007)
Novel Approaches to Central Nervous System White Matter
Many nerve cells in the body are covered with a protective sheath known as myelin, which allows fast conduction of nerve impulses, and which is produced by two different types of cells called oligodendrocytes and Schwann cells. Demyelination occurs when this protective covering is destroyed, resulting in impaired nerve function. While demyelination is most closely associated with Multiple Sclerosis, it is also implicated in other neurological and psychiatric conditions such as schizophrenia and spinal cord injuries. The term white matter is used to describe areas of the brain and spinal cord that contain many myelinated nerve fibres, and it is the white matter that is responsible for information transmission in the body.
The goal of Dr. Miller and her team is to attempt to repair these damaged, demyelinated nerve cells using a stem cell-based approach. In this team’s research, oligodendrocyte and Schwann cell stem cells will be transplanted into an injured spinal cord in order to see if remyelination and subsequent improved nerve function will result. Not only will this generate information relevant to spinal cord injury, but will also assess if this transplantation method can be used more broadly in the treatment of other white matter disorders.
Additionally, research will be done on discovering how to regulate oligodendrocyte survival, in order to prevent the death of these important cells in neurodegenerative conditions, as well as to promote their survival following transplantation. These latter studies have the potential to lead to the future development of small molecule therapeutics to treat disorders where demyelination occurs, such as MS, schizophrenia and spinal cord injuries.
Transforming Research on Chronic Pain in Canada
Pain affects millions of people worldwide and has a profound negative effect on quality of life. Untreated pain is the most common cause of disability that impairs life. Acute pain is a normal sensation triggered by the nervous system to alert the body to an injury. Chronic pain, on the other hand, is a pain that lasts long after the usual recovery period of the initial injury or illness and may even be present without a cause. This sort of pain poses no known defensive or helpful function.
Neuropathic pain is a type of chronic pain that occurs after nerve injury or from disease, where the signs of original injury are gone. It is extremely debilitating and is resistant to available treatments. Neuropathic pain can be seen in patients with diabetes, cancer, HIV and other disorders.
The goal of Dr. Salter and his team is to gain new insights into the genetic, molecular and cellular mechanisms regarding why pain becomes chronic and how chronic pain information is stored and processed in the brain. This new knowledge will lead to advances in diagnostics, therapeutics and management for those suffering with neuropathic pain. The understanding of these mechanisms can lead to the development of a new generation of drugs aimed at selectively targeting and treating chronic pain and repairing damaged nervous function.
By showing altered brain function and genetic components in chronic pain, this research will help in reducing the severe stigmatization of people suffering from chronic pain. In addition, patients with neuropathic pain often suffer from depression secondarily and any improved pain control can improve mental health overall.
In a broader sense, the molecular mechanisms elucidated in this research are relevant in the study of other Central Nervous System disorders such Alzheimer’s disease, Parkinson’s disease and neuroinflammatory disease.
Novel Therapeutic Strategies To Repair Brain Abnormalities in Psychiatric Disorders
Communication between brain cells is essential for normal brain function. Healthy brain cells are controlled through chemical messengers that stimulate or inhibit brain activity. Current theories indicate that psychiatric disorders such as addiction, schizophrenia, autism and mental retardation evolve from an imbalance of these chemical messengers leading to a disruption in the way brain cells are able to communicate with each other.
Drugs currently available for the treatment of psychiatric disorders often target multiple receptors throughout the brain. Although these compounds have therapeutic efficacy in subgroups of patients, negative side effects often develop which limit their use. Accordingly, new Pharmacotherapies, designed to target more specific brain processes implicated in various aspects of psychiatric illness, are urgently needed.
Dr. Wang and his team are investigating a novel method for treating these disorders, whereby small peptides can target specific sub-cellular processes that disrupt the balance of chemical messengers and hence the normal communication between brain cells. Dysfunction of the normal communication between brain cells has been linked to psychiatric diseases and this new class of drugs is designed to restore normal function in a highly specific manner that will minimize negative side effects. The team’s initial focus is on developing a therapy for drug addiction, however the principles underlying the action of these new drugs could lead to the development of similar treatments for other neurological and neuropsychiatric illnesses, such as Alzheimer’s disease, autism, mental retardation and schizophrenia.