The fifty current members of the CENUM work on dozens of diseases that stem from defects in the development and/or functioning of the brain or the nervous system. Although these diseases are generally divided between neurology and psychiatry, the CENUM chose not to make this distinction. In fact, since the neuron is the basic cell type of the brain and the nervous system, the CENUM focuses its research activities on the development and functioning of this cell. The research topics that the CENUM members work on can be divided into different categories of diseases affecting different aspects of the nervous system.

Epilepsy 

Epilepsy is a disorder characterized by recurrent seizures that affect the functioning of the brain and that are expressed by chaotic electrical activity. There are two types of seizures: absence seizures, where the person experiences loss of consciousness for a few seconds, and tonic clonic seizures during which the body shakes and the extremities jerk and twitch. In Canada, close to 300,000 people have epilepsy and about 14,000 new cases are diagnosed each year, half of which are in children under ten. Over the past few years, researchers have identified mutations responsible for epilepsy in genes that play a role in the electrical transmission between neurons. In many cases, however, the cause of epilepsy remains unknown.

Neurodevelopmental Disorders 

The brain is one of the most complex organs of the human body. It consists of billions of specialized cells called neurons. Each one of these neurons makes close to ten thousand connections with neighbouring neurons through a particular structure called a synapse. The complete system of neurons and synapses forms a vast network of communication that covers the entire organism. This network allows us to control our daily gestures such as speech or walking, but it also regulates body temperature and makes our heart beat. During the development of an embryo, each neuron must reach a precise destination within the brain and nervous system and make the right connections with the right cells. Defects occurring during the migration of neurons or the establishment of connections are believed to be at the root of many neurodevelopmental diseases. Understanding brain development and identifying the defects associated with the diseases are two crucial stages of research in neuromics.

Stem cells that will become neurons will face several important decisions during brain development: proliferate or not, differentiate or not, establish connections or not. The molecular mechanisms that control these decisions are the basis for normal development and, ultimately, for proper functioning of the nervous system. The objective of research on brain development is to gain an understanding of the stages of development in order to be able to compensate for possible deficiencies caused by either a disease or an accident.

As mentioned before, neurodevelopmental diseases are anomalies in brain development caused by genetic, biological, and environmental factors. This group of diseases includes, among others, attention deficit hyperactive disorder, schizophrenia, obsessive-compulsive disorder, and autism. The exact causes of these diseases are still unknown and current research is aimed at identifying the genes involved in neurodevelopmental disorders. Synapses, the points of communication between neurons, play an important role in brain development and this is why current studies focus particularly on synaptic genes. The Synapse to Disease project was created specifically to identify those mutations in synaptic genes believed to be at the root of neurodevelopmental diseases.

- Autism
Autism is a neurological disorder affecting young children that typically appears within the first three years of life. It affects some 20 out of 10,000 people and is characterized by deficits in verbal and non-verbal communication, impaired social interaction, unusual patterns of behaviour, and restricted activities. On the one hand, autism research tries to better characterize the symptoms of the disorder and understand how they affect cognition. On the other hand, because there is a strong genetic component to the disorder, another objective is to identify the genes responsible for the disease.

- Mental retardation
Mental retardation is a disability characterized by below average intellectual functioning and deficits in the areas of learning, personal autonomy, and social responsibility. The cause of mental retardation remains unknown and research mainly focuses on identifying the genes responsible for it. With this knowledge we expect to be able to better understand the disorder and develop diagnostic tests.

- Schizophrenia
Schizophrenia is a psychiatric disease characterized by profound disturbances in cognition, behaviour, and emotions. The disease typically presents itself toward the end of adolescence or during early adulthood and affects up to 1% of the population. Even though there are drugs available to treat the symptoms of schizophrenia, its cause remains unknown. The fact that there is a genetic component to the disease has directed research in this area towards identifying the genes involved. Knowledge acquired through genetic analysis should lead to a better understanding of the biological basis of schizophrenia.

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Neuromuscular diseases 

Neuromuscular diseases affect the nerves that control the muscles responsible for voluntary movement such as those in the arms and the legs. Muscle contractions are generated by neurons in the neuromuscular junctions. When these neurons are affected by a disease, the communication between the nervous system and the muscles are compromised which then leads to the disease symptoms. The muscles usually then start to progressively weaken, resulting in a complete loss of muscle function in the long-term. Many neuromuscular diseases have genetic origins, which is why searching for mutations represents an important step in the understanding of these diseases. Neuromuscular diseases can also be caused by a disruption in the immune system, as is the case with multiple sclerosis. Since there is no medical cure for the majority of these diseases, current treatment is aimed at alleviating symptoms, increasing mobility and prolonging life. CENUM researchers work towards a better understanding of the following neuromuscular diseases:

- Amyotrophic Lateral Sclerosis
Amyotrophic Lateral Sclerosis (ALS), also known as Charcot’s Disease or Lou Gehrig's Disease, is a neurodegenerative disease that usually occurs around the age of fifty. About 5% of ALS cases have a genetic origin which led researchers to identify two genes, SOD1 and TDP-43, found to be responsible for the most common form of ALS. Current research takes place on two levels: identifying other genes and understanding how SOD1 and TDP-43 mutations cause the disease.

- Multiple Sclerosis
Multiple Sclerosis (MS) is an immune-mediated disease that affects the central nervous system and is characterized by a loss of myelin, the protective covering of the neurons in the white matter of the brain. The disease manifests itself through lesions that are responsible for symptoms such as a loss of visual acuity, motor deficits, and speech difficulties. Research on MS is aimed at a better understanding of how the nervous and immune systems interact to produce the symptoms and at studying the role of the blood-brain barrier in neuroimmunological diseases.

- Oculopharyngeal muscular dystrophy
Oculopharyngeal muscular dystrophy (OPMD) is a genetic muscle disease characterized by drooping of the upper eyelids (ptosis) and swallowing difficulties. It is a slowly progressing disease with an onset between the ages of 40 and 60. OPMD is caused by an increased number of CAG triplet repeats in the PABPN1 gene. The objective of the ongoing research is to understand how PABPN1 mutations affect normal functioning of cells and how they lead to the symptoms of the disease.

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Cerebrovascular Diseases 

Cerebrovascular diseases, also called neurovascular diseases, are the result of an incorrect functioning of the blood vessels that supply the brain. Intracranial aneurysms and cavernomas are two examples of cerebrovascular diseases. Because these diseases present a genetic component, the approach used is to identify the genes involved in order to better understand the emergence of these diseases.

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Traumatic Brain and Spinal Cord Injuries  

Traumatic Brain and Spinal Cord Injuries are often the result of motor vehicle accidents (in almost 50% of cases), sporting accidents, work-related accidents, household accidents, or aggression. The most common injuries include concussions, cerebral contusions, and deep coma, all of which produce an altered state of consciousness and a loss of cognitive, sensorimotor, and physiological capacities, as well as injuries to the spinal cord that cause paralysis. The objective of the research in this area is to better understand the effects of concussions on cognitive functions, attention, and memory and to identify new strategies to facilitate guidance and re-connection of spinal cord neurons.

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Learning Disabilities  

Learning Disabilities are impairments in the processes of perception, thought, memorization, or learning that affect the acquisition and use of oral and written language, of reading and writing, as well as mathematics, calculations, logical reasoning, and problem solving. Learning Disabilities are caused by a combination of factors (genetic, neurobiological, cerebral injury) and their manifestation differs greatly with each person. These disabilities can also be associated with other medical conditions such as attention disorders, behavioural and socio-affective disorders, and sensory impairments. The goal of research is to better characterize the observed impairments and to improve the understanding of the mechanisms leading to learning disabilities. Knowledge acquired in this area will allow for early intervention, which in turn will benefit personal development of affected individuals.

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Movement disorders  

Movement disorders are neurological impairments that affect speed, fluidity, quality, and ease of movements. The following diseases are all examples of movement disorders:

- Ataxia
Ataxia is characterized by a loss of balance, a lack of coordination and by difficulty in walking. It is the result of damage to the cerebellum, the area of the brain that controls movement. There are numerous forms of ataxia. Some are hereditary while others are caused by multiple sclerosis, neuropathy, or sometimes brain tumours. Current research focuses mainly on identifying genes responsible for the hereditary forms of ataxia and studying the mechanisms causing the symptoms of the disease.

- Dyskinesia
Dyskinesias are irregular, involuntary, and uncontrollable movements of the mouth and face. Tardive dyskinesia is caused by long-term use of certain drugs and it most frequently occurs in older people and patients treated with neuroleptic drugs. Studies have shown that dyskinesias are associated with anomalies of the basal ganglia and other regions of the brain. Research presently uses magnetic resonance spectroscopy to measure choline/creatine levels in order to determine their role in the disease. The long-term objective is to develop biological markers that will make it possible to diagnose dyskinesias and follow their evolution.

- Huntington Disease
Huntington disease is a hereditary neurodegenerative disease characterized by involuntary movements in several parts of the body. The disease results from the destruction of cells in the caudate nucleus and the putamen, two regions of the brain that control body movement. As it progresses, the disease also affects short-term memory, decision-making, and the control of emotions. By trying to understand how the disease generates movement problems, researchers hope to identify ways to treat the disease.

- Parkinson’s Disease
Parkinson’s Disease is a neurodegenerative disease generally affecting men over fifty. It manifests itself by resting tremor and abnormal muscle tone. Parkinson’s symptoms can be alleviated with L-Dopa but the drug is known to rapidly lose its efficiency. Research is aimed at better understanding the different symptoms related to the disease.

- Restless Legs Syndrome
Restless Legs Syndrome (RLS) is a neurological disease characterized by a sensation of agitation in the lower limbs. The syndrome intensifies at night or when the person is at rest. Studies have shown that, in many cases, RLS has a strong hereditary component. The present research tries to characterize the symptoms of the disease and identify the genes that cause it.

- Gilles-de-la-Tourette Syndrome
Gilles-de-la-Tourette Syndrome, also known as Tourette syndrome, is a complex neurological disease characterized by motor and vocal tics often associated with obsessive compulsive and attention deficit disorders. The objective of research is to characterize the different disorders associated with Tourette syndrome in order to find the genes that cause it.

- Tremors
As the name indicates, essential tremor is a neurological disease characterized by tremors, most frequently of the hands. Tremors are apparent when the affected person moves, for example to pick up a cup, but are not apparent when the person is sleeping or otherwise at rest. Two genes, ETM1 and ETM2, have been associated with the disease but they do not account for all cases of tremors. The objective of research in this area is to better characterize the symptoms in order to identify other genes.

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Brain Tumours 

Brain tumours are either caused by uncontrolled cell division in the cells and tissues that form the brain (neurons, lymphatic tissue, blood vessels, cranial nerves, meninges) or the consequence of metastases coming from other organs. Primary brain tumours, originating in the brain itself, affect about 8 out of 100,000 people while all brain tumours combined (both primary and metastatic) affect close to 32 out of 100,000 people. Research is aimed at better understanding the factors that influence the occurrence of brain tumours and finding new strategies to slow down their growth.

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