Molecular Medicine NATS 3034 Lecture 7 PDF

 Molecular Medicine NATS 3034 Lecture 7 Split into 5 different presentations 1 – Disorders of the Brain 2 – Genetics of Brain Disorders 3 – Power of Population Databases 4 – Molecular alterations driving disease 5 – Precision medicine – teaching old drugs new tricks Dr Natha...

 Molecular Medicine NATS 3034 Lecture 7 Split into 5 different presentations 1 – Disorders of the Brain 2 – Genetics of Brain Disorders 3 – Power of Population Databases 4 – Molecular alterations driving disease 5 – Precision medicine – teaching old drugs new tricks Dr Nathan Absalom [email protected]  Molecular Medicine NATS 3034 Lecture 7 Split into 5 different presentations 1 – Disorders of the Brain 2 – Genetics of Brain Disorders 3 – Power of Population Databases 4 – Molecular alterations driving disease 5 – Precision medicine – teaching old drugs new tricks Neurological Disorders Neurological disorders are a varied group of illnesses affecting the nervous system. This lecture will give an overview of the importance of some of these disorders in human health  The Significant Burden of Neurological Disorders Altogether, neurological disease is one of the largest burdens of disease worldwide. The neurological aspects of stroke and neonatal encephalopathy are secondary, with restricted oxygen to the brain as primary. The Lancet Neurology 2024 23344-381DOI: (10.1016/S1474-4422(24)00038-3)  The Significant Burden of Neurological Disorders The burden in Australia. Much of the burden is carried Notice the difference in by permanent disabilities, as well as early mortality defining burden and disorder types. Be careful to understand where epidemiological data comes from! Australian Institute of Health and Welfare, 2022 Current research into brain and developmental disorders Neurological diseases are the largest recipient of NHMRC research grant funding over the last decade. This is in part because of the disease burden, and in part because the treatment options are poor.  Types of Neurological Disorders Cerebrovascular diseases are not originated in the central nervous system. They are caused by a lack of Cerebrovascular disease oxygen to the brain, but the damage they cause is to the central nervous system.  Where is stroke research directed? Research centres around two central questions. How can stroke be prevented, and how to recover from Cerebrovascular disease stroke? Although there have been isolated incidents, there is no “wonder drug” to cure neuronal death.  Neurodegenerative Disorders Neurodegenerative disorders are progressive disorders. Often at later age, they are caused by slow, progressive Neurodegenerative Diseases loss of neurons, sometimes in specific regions. The two most known are Parkinson’s and Alzheimer’s Disease.  Research into Neurodegenerative Disorders Much research is targeted toward the identification of Neurodegenerative Diseases biomarkers. This is where clinical samples are taken at different disease stages to try and make earlier diagnosis where patients are more amenable to treatment.  Rare Neurological Diseases Rare diseases are mostly genetic disorders with a distinct cause and pathology. Much of the disease Rare Diseases burden comes from de novo variants causing disorders beginning in infancy or childhood.  Monogenic, polygenic and acquired disorders The cause of different disorders is important to Rare Diseases understand, and may be related to treatment. Often, severe rare forms of a disease have a single gene cause, while more common and milder forms are polygenic  Monogenic, polygenic and acquired disorders Genetics has really changed the way we look at epilepsy Rare Diseases over the last 30 years. We used to call them “idiopathic”, or no known cause, but now we understand that most of these epilepsies are genetic in origin.  Epilepsies are a collection of different diseases A key characteristic of early-onset epilepsies is that they Because epilepsies strike the are so diverse. Different seizure types, different very young the most severely, comorbidities and response to treatment. the estimated lost years of life is very large, even though the disease is more rare.  Epilepsy and neurodevelopmental disorders The epilepsy syndrome is based on the age you develop Classification is key to seizures and developing molecular medicines. What happens when you give the same drug to people with variants in different genes?  Research into severe epilepsies This approach is based on identifying the molecular cause Research into epilepsies has of the disorder in each patient, then working towards moved towards a precision treatments targeted to the individual. medicine approach. Patient Sequence In silico with rare and identify analysis to disease gene determine pathogenicity Electrophysiological and functional Physiology and analysis Cohort drug analysis preclinical drug or clinical trial development