Rare Neurodegenerative Disease: At the Molecular Level<\/h1><\/div><\/div><\/div>We target neurological pathologies using novel genome editing techniques<\/p>\n<\/div><\/div><\/div><\/div><\/div>
Tay-Sachs disease<\/h2><\/div><\/div><\/div>Tay-Sachs disease is caused by mutations in the HEXA gene which encodes the alpha-subunit of the enzyme beta-hexosaminidase A. This is a lysosomal enzyme responsible for breaking down a cell membrane lipid called GM2 ganglioside. As a result of this mutation, the enzyme becomes dysfunctional leading to the accumulation of GM2 ganglioside, principally in central nervous system neurons. This causes neuronal dysfunction and death, which ultimately manifests as symptoms ranging from involuntary muscle twitches, vision and hearing loss, intellectual disability and seizures.<\/p>\n
Our lab has generated a murine model of Tay-Sachs disease and is beginning to implement CRISPR-Cas 9 based therapeutics to target and correct the mutation.<\/p>\n<\/div><\/div><\/div>
![\"schematic](\"https:\/\/lab.research.sickkids.ca\/ivakine\/wp-content\/uploads\/sites\/144\/2023\/07\/2-Untitled-slide-4.png\")
<\/span><\/div><\/div><\/div><\/div><\/div>Niemann-Pick disease type C<\/h2><\/div><\/div><\/div>Niemann-Pick disease type C is a metabolic disorder characterized by the abnormal accumulation of lipids, such as cholesterol and glycosphingolipids, within cells. This accumulation primarily affects the liver, spleen, and brain and is largely caused by irregularities in lysosomal storage and trafficking. The combined effects of these physiological abnormalities manifest as progressive and fatal neurodegeneration in NPC patients.<\/p>\n
Our lab focuses on mutations in the NPC1 and NPC2 gene which play a role in lipid trafficking, transport and storage.<\/p>\n<\/div><\/div><\/div>
![\"schematic](\"https:\/\/lab.research.sickkids.ca\/ivakine\/wp-content\/uploads\/sites\/144\/2023\/07\/NPC1-1.png\")
<\/span><\/div><\/div><\/div><\/div><\/div>Progranulin-deficient frontotemporal dementia<\/h2><\/div><\/div><\/div>Frontotemporal dementia is a common cause of dementia that occurs due to the damage and eventual death of neurons located in the frontal and temporal lobes of the brain. This progressive cerebral atrophy can cause changes to behaviour and personality as well as nonfluent aphasia. Our lab focuses on progranulin-deficient frontotemporal dementia, which arises due to the lack of a highly conserved protein called progranulin. Progranulin plays a role in cell growth, survival and repair and is implicated in this inherited form of dementia.<\/p>\n
Currently, our lab is using a CRIPSR-Cas 9 to upregulate progranulin in murine models, in hopes to understand more about the disease phenotype and potential therapeutics.<\/p>\n<\/div><\/div><\/div>
![\"schematic](\"https:\/\/lab.research.sickkids.ca\/ivakine\/wp-content\/uploads\/sites\/144\/2023\/07\/3-Untitled-slide-1.png\")
<\/span><\/div><\/div><\/div><\/div><\/div>Joubert-like syndrome<\/h2><\/div><\/div><\/div>Joubert-like syndrome is predominantly an autosomal recessive disorder. It can be caused by mutations in several genes, and is part of a larger group of disorders called \u2018ciliopathies\u2019. Ciliopathies affect cellular structures called cilia, which are microtubule-based, cytoplasmic extensions which are critical for developmental and physiological functions. Joubert syndrome affects the brain and is characterized by the appearance of a typical \u2018molar tooth sign\u2019 on MRI. Therefore, affected individuals often display intellectual disability. Many other parts of the body can be affected as well, and symptoms can include weak muscle tone, abnormal breathing patterns, and abnormal eye movements.<\/p>\n
Our goal is to investigate the significance of clinical variants in new genes and develop better therapeutic strategies for affected individuals.<\/p>\n<\/div><\/div><\/div>
![\"Figure](\"https:\/\/lab.research.sickkids.ca\/ivakine\/wp-content\/uploads\/sites\/144\/2023\/07\/figure-8-joubert.jpg\")
<\/span><\/div>
We target neurological pathologies using novel genome editing techniques<\/p>\n<\/div><\/div><\/div><\/div><\/div>
Tay-Sachs disease<\/h2><\/div><\/div><\/div>Tay-Sachs disease is caused by mutations in the HEXA gene which encodes the alpha-subunit of the enzyme beta-hexosaminidase A. This is a lysosomal enzyme responsible for breaking down a cell membrane lipid called GM2 ganglioside. As a result of this mutation, the enzyme becomes dysfunctional leading to the accumulation of GM2 ganglioside, principally in central nervous system neurons. This causes neuronal dysfunction and death, which ultimately manifests as symptoms ranging from involuntary muscle twitches, vision and hearing loss, intellectual disability and seizures.<\/p>\n
Our lab has generated a murine model of Tay-Sachs disease and is beginning to implement CRISPR-Cas 9 based therapeutics to target and correct the mutation.<\/p>\n<\/div><\/div><\/div>
<\/span><\/div><\/div><\/div><\/div><\/div>Niemann-Pick disease type C<\/h2><\/div><\/div><\/div>Niemann-Pick disease type C is a metabolic disorder characterized by the abnormal accumulation of lipids, such as cholesterol and glycosphingolipids, within cells. This accumulation primarily affects the liver, spleen, and brain and is largely caused by irregularities in lysosomal storage and trafficking. The combined effects of these physiological abnormalities manifest as progressive and fatal neurodegeneration in NPC patients.<\/p>\n
Our lab focuses on mutations in the NPC1 and NPC2 gene which play a role in lipid trafficking, transport and storage.<\/p>\n<\/div><\/div><\/div>
<\/span><\/div><\/div><\/div><\/div><\/div>Progranulin-deficient frontotemporal dementia<\/h2><\/div><\/div><\/div>Frontotemporal dementia is a common cause of dementia that occurs due to the damage and eventual death of neurons located in the frontal and temporal lobes of the brain. This progressive cerebral atrophy can cause changes to behaviour and personality as well as nonfluent aphasia. Our lab focuses on progranulin-deficient frontotemporal dementia, which arises due to the lack of a highly conserved protein called progranulin. Progranulin plays a role in cell growth, survival and repair and is implicated in this inherited form of dementia.<\/p>\n
Currently, our lab is using a CRIPSR-Cas 9 to upregulate progranulin in murine models, in hopes to understand more about the disease phenotype and potential therapeutics.<\/p>\n<\/div><\/div><\/div>
<\/span><\/div><\/div><\/div><\/div><\/div>Joubert-like syndrome<\/h2><\/div><\/div><\/div>Joubert-like syndrome is predominantly an autosomal recessive disorder. It can be caused by mutations in several genes, and is part of a larger group of disorders called \u2018ciliopathies\u2019. Ciliopathies affect cellular structures called cilia, which are microtubule-based, cytoplasmic extensions which are critical for developmental and physiological functions. Joubert syndrome affects the brain and is characterized by the appearance of a typical \u2018molar tooth sign\u2019 on MRI. Therefore, affected individuals often display intellectual disability. Many other parts of the body can be affected as well, and symptoms can include weak muscle tone, abnormal breathing patterns, and abnormal eye movements.<\/p>\n
Our goal is to investigate the significance of clinical variants in new genes and develop better therapeutic strategies for affected individuals.<\/p>\n<\/div><\/div><\/div>
<\/span><\/div>
Tay-Sachs disease is caused by mutations in the HEXA gene which encodes the alpha-subunit of the enzyme beta-hexosaminidase A. This is a lysosomal enzyme responsible for breaking down a cell membrane lipid called GM2 ganglioside. As a result of this mutation, the enzyme becomes dysfunctional leading to the accumulation of GM2 ganglioside, principally in central nervous system neurons. This causes neuronal dysfunction and death, which ultimately manifests as symptoms ranging from involuntary muscle twitches, vision and hearing loss, intellectual disability and seizures.<\/p>\n
Our lab has generated a murine model of Tay-Sachs disease and is beginning to implement CRISPR-Cas 9 based therapeutics to target and correct the mutation.<\/p>\n<\/div><\/div><\/div>
<\/span><\/div><\/div><\/div><\/div><\/div>Niemann-Pick disease type C<\/h2><\/div><\/div><\/div>Niemann-Pick disease type C is a metabolic disorder characterized by the abnormal accumulation of lipids, such as cholesterol and glycosphingolipids, within cells. This accumulation primarily affects the liver, spleen, and brain and is largely caused by irregularities in lysosomal storage and trafficking. The combined effects of these physiological abnormalities manifest as progressive and fatal neurodegeneration in NPC patients.<\/p>\n
Our lab focuses on mutations in the NPC1 and NPC2 gene which play a role in lipid trafficking, transport and storage.<\/p>\n<\/div><\/div><\/div>
<\/span><\/div><\/div><\/div><\/div><\/div>Progranulin-deficient frontotemporal dementia<\/h2><\/div><\/div><\/div>Frontotemporal dementia is a common cause of dementia that occurs due to the damage and eventual death of neurons located in the frontal and temporal lobes of the brain. This progressive cerebral atrophy can cause changes to behaviour and personality as well as nonfluent aphasia. Our lab focuses on progranulin-deficient frontotemporal dementia, which arises due to the lack of a highly conserved protein called progranulin. Progranulin plays a role in cell growth, survival and repair and is implicated in this inherited form of dementia.<\/p>\n
Currently, our lab is using a CRIPSR-Cas 9 to upregulate progranulin in murine models, in hopes to understand more about the disease phenotype and potential therapeutics.<\/p>\n<\/div><\/div><\/div>
<\/span><\/div><\/div><\/div><\/div><\/div>Joubert-like syndrome<\/h2><\/div><\/div><\/div>Joubert-like syndrome is predominantly an autosomal recessive disorder. It can be caused by mutations in several genes, and is part of a larger group of disorders called \u2018ciliopathies\u2019. Ciliopathies affect cellular structures called cilia, which are microtubule-based, cytoplasmic extensions which are critical for developmental and physiological functions. Joubert syndrome affects the brain and is characterized by the appearance of a typical \u2018molar tooth sign\u2019 on MRI. Therefore, affected individuals often display intellectual disability. Many other parts of the body can be affected as well, and symptoms can include weak muscle tone, abnormal breathing patterns, and abnormal eye movements.<\/p>\n
Our goal is to investigate the significance of clinical variants in new genes and develop better therapeutic strategies for affected individuals.<\/p>\n<\/div><\/div><\/div>
<\/span><\/div>
Niemann-Pick disease type C is a metabolic disorder characterized by the abnormal accumulation of lipids, such as cholesterol and glycosphingolipids, within cells. This accumulation primarily affects the liver, spleen, and brain and is largely caused by irregularities in lysosomal storage and trafficking. The combined effects of these physiological abnormalities manifest as progressive and fatal neurodegeneration in NPC patients.<\/p>\n
Our lab focuses on mutations in the NPC1 and NPC2 gene which play a role in lipid trafficking, transport and storage.<\/p>\n<\/div><\/div><\/div>
<\/span><\/div><\/div><\/div><\/div><\/div>Progranulin-deficient frontotemporal dementia<\/h2><\/div><\/div><\/div>Frontotemporal dementia is a common cause of dementia that occurs due to the damage and eventual death of neurons located in the frontal and temporal lobes of the brain. This progressive cerebral atrophy can cause changes to behaviour and personality as well as nonfluent aphasia. Our lab focuses on progranulin-deficient frontotemporal dementia, which arises due to the lack of a highly conserved protein called progranulin. Progranulin plays a role in cell growth, survival and repair and is implicated in this inherited form of dementia.<\/p>\n
Currently, our lab is using a CRIPSR-Cas 9 to upregulate progranulin in murine models, in hopes to understand more about the disease phenotype and potential therapeutics.<\/p>\n<\/div><\/div><\/div>
<\/span><\/div><\/div><\/div><\/div><\/div>Joubert-like syndrome<\/h2><\/div><\/div><\/div>Joubert-like syndrome is predominantly an autosomal recessive disorder. It can be caused by mutations in several genes, and is part of a larger group of disorders called \u2018ciliopathies\u2019. Ciliopathies affect cellular structures called cilia, which are microtubule-based, cytoplasmic extensions which are critical for developmental and physiological functions. Joubert syndrome affects the brain and is characterized by the appearance of a typical \u2018molar tooth sign\u2019 on MRI. Therefore, affected individuals often display intellectual disability. Many other parts of the body can be affected as well, and symptoms can include weak muscle tone, abnormal breathing patterns, and abnormal eye movements.<\/p>\n
Our goal is to investigate the significance of clinical variants in new genes and develop better therapeutic strategies for affected individuals.<\/p>\n<\/div><\/div><\/div>
<\/span><\/div>
Frontotemporal dementia is a common cause of dementia that occurs due to the damage and eventual death of neurons located in the frontal and temporal lobes of the brain. This progressive cerebral atrophy can cause changes to behaviour and personality as well as nonfluent aphasia. Our lab focuses on progranulin-deficient frontotemporal dementia, which arises due to the lack of a highly conserved protein called progranulin. Progranulin plays a role in cell growth, survival and repair and is implicated in this inherited form of dementia.<\/p>\n
Currently, our lab is using a CRIPSR-Cas 9 to upregulate progranulin in murine models, in hopes to understand more about the disease phenotype and potential therapeutics.<\/p>\n<\/div><\/div><\/div>
<\/span><\/div><\/div><\/div><\/div><\/div>Joubert-like syndrome<\/h2><\/div><\/div><\/div>Joubert-like syndrome is predominantly an autosomal recessive disorder. It can be caused by mutations in several genes, and is part of a larger group of disorders called \u2018ciliopathies\u2019. Ciliopathies affect cellular structures called cilia, which are microtubule-based, cytoplasmic extensions which are critical for developmental and physiological functions. Joubert syndrome affects the brain and is characterized by the appearance of a typical \u2018molar tooth sign\u2019 on MRI. Therefore, affected individuals often display intellectual disability. Many other parts of the body can be affected as well, and symptoms can include weak muscle tone, abnormal breathing patterns, and abnormal eye movements.<\/p>\n
Our goal is to investigate the significance of clinical variants in new genes and develop better therapeutic strategies for affected individuals.<\/p>\n<\/div><\/div><\/div>
<\/span><\/div>
Joubert-like syndrome is predominantly an autosomal recessive disorder. It can be caused by mutations in several genes, and is part of a larger group of disorders called \u2018ciliopathies\u2019. Ciliopathies affect cellular structures called cilia, which are microtubule-based, cytoplasmic extensions which are critical for developmental and physiological functions. Joubert syndrome affects the brain and is characterized by the appearance of a typical \u2018molar tooth sign\u2019 on MRI. Therefore, affected individuals often display intellectual disability. Many other parts of the body can be affected as well, and symptoms can include weak muscle tone, abnormal breathing patterns, and abnormal eye movements.<\/p>\n
Our goal is to investigate the significance of clinical variants in new genes and develop better therapeutic strategies for affected individuals.<\/p>\n<\/div><\/div><\/div>
<\/span><\/div>![\"Schematic](\"https:\/\/lab.research.sickkids.ca\/ivakine\/wp-content\/uploads\/sites\/144\/2023\/07\/2-Untitled-slide-1.png\")
<\/span><\/div><\/div><\/div><\/div><\/div>![\"Schematic](\"https:\/\/lab.research.sickkids.ca\/ivakine\/wp-content\/uploads\/sites\/144\/2023\/07\/Website-Graphics-1.png\")
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