Lecture.10 Gene Therapy for Neurological Disorders: Introduction
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This document appears to be a lecture presentation on gene therapy for neurological disorders given by Qurat-ul-Ain, B. Pharm., M. Phil., Ph.D. It includes an introduction to the topic, mentions that it is the 10th lecture in the series, and provides contact information for Qurat-ul-Ain. The document also includes slides on topics like what a brain tumor is, the different types of brain tumors, glioblastoma, and the genes involved in different types of glioblastoma. It concludes by thanking the audience.
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GENE THERPY & CELL BASED THERAPY FOR CNS DISORDERS
1. WHAT IS GENE THERAPY
2. PRINCIPLE OF GENE THERAPY
3. TYPES OF GENE THERAPY
4. VECTORS IN GENE DELIVERY SYSTEM
5. ROLE OF GENE THERAPY IN CNS DISORDERS
6. GENE THERAPY FOR ALZHEIMERS DISEASE
7. GENE THERAPY FOR AMYOTROPIC LATERAL SCLEROSIS
8. GENE THERAPY FOR STROKE
9. CELL THERAPY FOR CNS DISORDERS
10. CELL THERAPY STRATEGIES
11. CELL THERAPY FOR PARKINSON
12. CELL THERAPY FOR HUNTINGTONS DISEASE
13. CRISPR/CAS9
What is Epigenetics?
"Epigenetics refers to genetic factors that change an organism’s appearance or biological functions without changing the actual DNA sequence. In other words, gene expression changes but the genes themselves don’t. Epigenetics adds an additional level of complexity to the genetic code." - Public Health Cafe
Epigenetic
This document discusses epigenetics and provides an overview of key concepts. It begins with a brief history of epigenetics research from the 1940s to present day. It then defines epigenetics as the study of heritable alterations in gene expression that do not involve changes to DNA sequence. Several epigenetic mechanisms are identified, including DNA methylation, histone modification, and non-coding RNA. The document notes that epigenetic changes are involved in various diseases and disorders. It also discusses how environmental, behavioral, dietary, and psychological factors can influence epigenetics.
Stem cell therapy in neurological diseases
This document discusses stem cell types and their potential applications for treating neurological diseases. It describes embryonic stem cells as pluripotent and able to differentiate into almost any cell type. Adult stem cells are multipotent and can only produce a limited range of cell types. Neural stem cells are discussed as a promising source for cell replacement therapies for conditions like Parkinson's disease. Challenges and limitations of stem cell therapies are also outlined.
Stem cell therapy neurological disorders
Stem cell therapy shows promise for treating various neurological disorders. There are two main types of stem cells - embryonic stem cells which are pluripotent, and adult stem cells which are multipotent. Stem cells may promote cell replacement in damaged organs through proliferation, migration, and differentiation. Challenges include optimal cell types and doses, monitoring transplanted cells, and ensuring safety. While stem cell therapy is being studied for conditions like Alzheimer's, Parkinson's, ALS, and stroke, more research is still needed to address current obstacles in translating laboratory findings to clinical applications.
Role of p53 gene
Majority of cancer lead by point mutation in p53 gene. which is also known as "guardian of genome". this mutation leads conversion of normal cell into cancerous cell.
Gene therapy for the treatment of cystic fibrosis
Gene therapy shows promise for treating cystic fibrosis, a genetic disorder caused by mutations in the CFTR gene. Researchers have conducted over 25 clinical trials using viral vectors like adenovirus to deliver functioning CFTR genes directly to the lungs, but trials were unsuccessful due to immune responses. More recent trials use non-viral gene therapy approaches like nebulizer sprays of liposome-encapsulated CFTR plasmid DNA, which show better results by avoiding immune system activation. Gene therapy aims to complement current cystic fibrosis treatments that manage symptoms but do not cure the underlying genetic cause of disease.
Induced pluripotent stem cells
The document discusses induced pluripotent stem cells (iPSCs), which are derived from adult somatic cells that are reprogrammed by introducing genes associated with pluripotency. iPSCs were first generated in 2006 and resemble embryonic stem cells. They can be produced from a person's own cells and have potential applications in disease modeling, drug development, and regenerative medicine without ethical issues associated with embryonic stem cells.
Recommended
GENE THERPY & CELL BASED THERAPY FOR CNS DISORDERS
1. WHAT IS GENE THERAPY
2. PRINCIPLE OF GENE THERAPY
3. TYPES OF GENE THERAPY
4. VECTORS IN GENE DELIVERY SYSTEM
5. ROLE OF GENE THERAPY IN CNS DISORDERS
6. GENE THERAPY FOR ALZHEIMERS DISEASE
7. GENE THERAPY FOR AMYOTROPIC LATERAL SCLEROSIS
8. GENE THERAPY FOR STROKE
9. CELL THERAPY FOR CNS DISORDERS
10. CELL THERAPY STRATEGIES
11. CELL THERAPY FOR PARKINSON
12. CELL THERAPY FOR HUNTINGTONS DISEASE
13. CRISPR/CAS9
What is Epigenetics?
"Epigenetics refers to genetic factors that change an organism’s appearance or biological functions without changing the actual DNA sequence. In other words, gene expression changes but the genes themselves don’t. Epigenetics adds an additional level of complexity to the genetic code." - Public Health Cafe
Epigenetic
This document discusses epigenetics and provides an overview of key concepts. It begins with a brief history of epigenetics research from the 1940s to present day. It then defines epigenetics as the study of heritable alterations in gene expression that do not involve changes to DNA sequence. Several epigenetic mechanisms are identified, including DNA methylation, histone modification, and non-coding RNA. The document notes that epigenetic changes are involved in various diseases and disorders. It also discusses how environmental, behavioral, dietary, and psychological factors can influence epigenetics.
Stem cell therapy in neurological diseases
This document discusses stem cell types and their potential applications for treating neurological diseases. It describes embryonic stem cells as pluripotent and able to differentiate into almost any cell type. Adult stem cells are multipotent and can only produce a limited range of cell types. Neural stem cells are discussed as a promising source for cell replacement therapies for conditions like Parkinson's disease. Challenges and limitations of stem cell therapies are also outlined.
Stem cell therapy neurological disorders
Stem cell therapy shows promise for treating various neurological disorders. There are two main types of stem cells - embryonic stem cells which are pluripotent, and adult stem cells which are multipotent. Stem cells may promote cell replacement in damaged organs through proliferation, migration, and differentiation. Challenges include optimal cell types and doses, monitoring transplanted cells, and ensuring safety. While stem cell therapy is being studied for conditions like Alzheimer's, Parkinson's, ALS, and stroke, more research is still needed to address current obstacles in translating laboratory findings to clinical applications.
Role of p53 gene
Majority of cancer lead by point mutation in p53 gene. which is also known as "guardian of genome". this mutation leads conversion of normal cell into cancerous cell.
Gene therapy for the treatment of cystic fibrosis
Gene therapy shows promise for treating cystic fibrosis, a genetic disorder caused by mutations in the CFTR gene. Researchers have conducted over 25 clinical trials using viral vectors like adenovirus to deliver functioning CFTR genes directly to the lungs, but trials were unsuccessful due to immune responses. More recent trials use non-viral gene therapy approaches like nebulizer sprays of liposome-encapsulated CFTR plasmid DNA, which show better results by avoiding immune system activation. Gene therapy aims to complement current cystic fibrosis treatments that manage symptoms but do not cure the underlying genetic cause of disease.
Induced pluripotent stem cells
The document discusses induced pluripotent stem cells (iPSCs), which are derived from adult somatic cells that are reprogrammed by introducing genes associated with pluripotency. iPSCs were first generated in 2006 and resemble embryonic stem cells. They can be produced from a person's own cells and have potential applications in disease modeling, drug development, and regenerative medicine without ethical issues associated with embryonic stem cells.
Mitochondrial disorders overview
- Mitochondrial diseases are caused by mutations in mitochondrial DNA (mtDNA) and can affect multiple organ systems. They are characterized by failure of mitochondria to produce sufficient energy for cells.
- mtDNA is inherited solely from mothers and can be heteroplasmic, containing both mutated and normal mtDNA. This explains varying severity between mothers and children.
- The patient described presented with encephalopathy, lactic acidosis, strokes and other multi-system involvement consistent with a mitochondrial disorder. Whole mitochondrial genome sequencing detected a mtDNA deletion of unknown extent/genes involved.
- When evaluating for possible mitochondrial disease, consider if a patient has an unexplained combination of features like lactic acidosis,
Gene medicine by kk sahu sir
INTRODUCTION
DNA VACCINES
GENE THERAPY
TIME LINE OF DEVELOPING GENE THERAPY
GENE THERAPY STRATEGIES
TECHNOLOGY OF CLASSICAL GENE THERAPY
PRINCIPLES OF GENE TRANSFER
VECTORS
VIRAL VECTORS
NON-VIRAL VECTORS
APPLICATIONS OF GENE THERAPY
ETHICAL IMPLICATIONS
THE FUTURE
CONCLUSION
REFERENCES
Regulation by Wnt Signaling
The Wnt cascade has emerged as a critical regulator of stem cells. In many tissues, activation of Wnt signaling has also been found to be associated with cancer. Understanding the regulation by Wnt signaling may serve as a paradigm for understanding the dual nature of self-renewal signals.
Genetics of mitochondrial diseases
Dr. Gayathri N. chaired a presentation by Dr. Govindaraju C. on mitochondrial genetics and diseases. The 3-sentence summary is:
The presentation covered the basics of mitochondrial genetics including structure, inheritance, and respiratory chain; it classified mitochondrial diseases into those caused by nuclear DNA and mtDNA mutations. Mitochondrial diseases can affect multiple organ systems and be caused by mutations in respiratory chain complexes or assembly factors, with phenotypes including Leigh syndrome, cardiomyopathy, leukodystrophy, and optic atrophy.
Stem cell therapy in neurological disorder
Stem cell therapy shows promise for treating neurological diseases. Various stem cell sources like embryonic stem cells, induced pluripotent stem cells, and adult neural stem cells can differentiate into neural cells and may be able to replace damaged or dead cells. Clinical trials have been conducted for conditions like Parkinson's disease and stroke with some patients showing improvements, but larger trials are still needed to confirm efficacy and safety. Challenges remain in ensuring stem cells engraft and properly differentiate in the brain.
Oncogene and tumor suppressor gene
Oncogene And Tumor Suppressor Gene
The document discusses oncogenes and tumor suppressor genes. It defines proto-oncogenes as genes involved in cell growth that can become activated oncogenes through mutations. Oncogenes are classified into five groups. Tumor suppressor genes normally inhibit tumor formation but mutations inactivate this function in a two-hit model. Examples discussed include HER2/neu, Ras, Myc, Rb, p53, BRCA1, BRCA2, and APC.
Mitochondrial Disorder
Mitochondrial diseases are caused by defects in the mitochondria or mitochondrial genome. The mitochondria produce energy in cells through oxidative phosphorylation and have important roles in calcium regulation, apoptosis, and reactive oxygen species generation. Mitochondrial DNA mutations can cause a variety of clinical syndromes affecting high-energy tissues like brain, muscle, heart. Common syndromes include MELAS, MERRF, and Leigh syndrome. Diagnosis involves assessing clinical features, blood/CSF lactate levels, muscle biopsy showing ragged red fibers, and genetic testing. Treatment focuses on managing symptoms while avoiding metabolic stress.
Mitochondrial disorders
A mitochondrion (singular of mitochondria) is part of every cell in the body that contains genetic material.
Mitochondria are responsible for processing oxygen and converting substances from the foods we eat into energy for essential cell functions.
The mitochondria of the zygote come from the oocyte, that is, from the mother and almost never from the sperm, form of transmission is called maternal inheritance
Which mitochondrial gene is mutated.
The extent of replicative segregation of the mutant mitochondrial genome during the early stages of embryonic development.
The abundance of the mutant mitochondrial gene in a particular tissue.
The threshold level of mutant mitochondrial DNA required in a tissue before an abnormality is evident clinically
Mitochondrial disease affects tissues most highly dependent on ATP production
*Nerves
*Muscles
Endocrine
Kidney
Low energy-requiring tissues are rarely directly affected, but may be secondarily
Lung
Connective tissue
Symptoms can be intermittent
Increased energy demand (illness, exercise)
Decreased energy supply (fasting)
Common feature
myoclonus epilepsy, deafness, blindness, anemia, diabetes, seizures and loss of cerebral blood supply (stroke).
Myoclonic epilepsy and ragged-red fiber disease (MERRF)
MERRF is a member of a group of disorders called mitochondrial encephalomyopathies that feature mitochondrial defects with altered brain and muscle functions.
The term “ragged red fibers” refers to large clumps of abnormal mitochondria that accumulate mostly in muscle cells and are stained red by a dye that is specific for complex II of the electron transport chain.
rare, maternally inherited, heteroplasmic, (point mutation in tRNA lysine gene)
Mutation is MTTK*MERRF8344G.
MT means mitochondrial gene is mutated
T means transfer RNA gene
K means the single-letter amino acid designation for lysine
MERRF means the clinical features
8344G means the mutant nucleotide is guanine (G) at nucleotide position 8344
If 90% of the mitochondria in nerve and muscle cells carry the MTTK*MERRF8344G mutation, then the defining symptoms of MERRF are present.
Maternally inherited mitochondrial disease
The MTTL1*MELAS3243G mutation accounts for more than 80% of the cases of MELAS.
This base substitution is in one of the two mitochondrial transfer RNALeu genes.
the A3243G mutation occurs in thetRNALeu(UUR) gene
When this mutation is present in ≥90% of the mitochondrial DNA of muscle tissue, there is an increased likelihood of recurrent strokes, dementia, epilepsy, and ataxia.
When heteroplasmy for the A3243G mutation
is ~40% to 50%, chronic progressive external ophthalmoplegia (CPEO), myopathy, and deafness are likely to occur.
Other MELAS mutations occur at sites 3252, 3271, and 3291 within the tRNALeu(UUR) gene and in the mitochondrial tRNAVal (MTTV) and COX III (MTCO3) genes.
Reduced activities in Complexes I and IV are established
Huntington
Huntington's disease is a neurodegenerative genetic disorder that causes the progressive breakdown of nerve cells in the brain, especially in the basal ganglia. It affects movement, cognition, and psychiatric functions and is caused by a defective gene inherited from a parent. Symptoms typically appear between ages 30-50 and include involuntary movements, cognitive decline, and psychiatric issues like depression. While there is no cure, treatment aims to reduce symptoms and complications through medications, speech/occupational/physical therapy, and supportive care.
STEM CELL CULTURE
This document discusses stem cell culture and provides definitions, classifications, and methods for culturing different types of stem cells. It summarizes the history of stem cell research from 1981 to present. It describes embryonic stem cells, adult stem cells including bone marrow and umbilical cord stem cells. Methods are outlined for isolating and culturing stem cells from bone marrow and umbilical cord. Advantages and disadvantages of different stem cell sources are compared.
Epigenetics
Epigenetics involves heritable changes in gene expression that are not caused by changes in the underlying DNA sequence. These changes are caused by mechanisms such as chromatin remodeling and DNA methylation. While genetics is determined by the DNA sequence, epigenetics influences which genes are expressed through modifications to histone proteins and DNA. These epigenetic modifications play important roles in development and can cause diseases if disrupted, such as imprinting disorders. Significant research is being conducted worldwide at top institutions like Johns Hopkins University to better understand epigenetics and its effects.
Epigenetics
This presentation on Epigenetics is most advanced and evidence based one. Its Very helpful for Genetics students and research fellows, Reproductive Medicine specialist, Reproductive Biologist, Infertility practitioners
Epigenetics
This document defines epigenetics as heritable changes in gene expression that are not caused by changes in DNA sequence. It discusses genomic imprinting, where alleles from the father and mother are expressed differently. Genomic imprinting is explained by the parental conflict theory, which posits that genes have evolved conflicting interests in how much they provision offspring depending on whether they are inherited from the father or mother. Imprinting marks on DNA are established differently depending on the parent of origin and can be erased in germ line cells, but reestablished in offspring. Problems can occur if imprinting marks are defective or the wrong parental alleles are inherited.
Human genome project 1
The document discusses the history and goals of the Human Genome Project, which began in 1990 with the aim of identifying all human genes and determining the sequence of DNA base pairs. Some key goals were to map all genes, determine DNA sequences, and address ethical issues. The project was completed earlier than expected in 2003 and has led to over 1,800 disease genes being discovered and many medical benefits like new diagnostic tests.
Stem cell therapy
Stem cell therapy holds promise for treating many incurable diseases by replacing damaged cells. There are various types of stem cells including embryonic, adult, and induced pluripotent stem cells. While embryonic stem cells can differentiate into any cell type, their use is controversial due to requiring embryo destruction. Alternative sources like adult stem cells and iPS cells do not have the same ethical issues but may have limitations. Stem cell research faces challenges like preventing immune rejection and tumor formation but continues to advance regenerative medicine.
Epigenetics
C.H. Waddington coined the term "epigenetics" in the 1940s to describe how environmental influences can affect gene expression and phenotypic traits. Epigenetics is the study of reversible modifications to DNA and chromatin that regulate gene expression in response to environmental factors without changing DNA sequences. The epigenome refers to the unique patterns of gene expression established in different cell types through DNA methylation, histone modifications, and noncoding RNAs. These epigenetic marks can be transmitted from parent cells to daughter cells and between generations.
Neuronal stem cellfi
This document provides an overview of neural stem cells (NSCs). It discusses the location and development of NSCs in the central nervous system. Key cell signaling pathways that regulate NSCs, such as Notch and WNT, are described. Common markers used to identify NSCs are discussed, including Nestin, Sox2, Musashi-1, Pax6, and CD133. Factors that affect the growth and multiplication of NSCs, such as growth factors EGF and FGF, are outlined. Methods for isolating and culturing NSCs are presented. Finally, potential therapeutic applications of NSCs are reviewed, along with some current clinical trials utilizing NSCs.
Single gene disorders
This document discusses several single-gene disorders including cystic fibrosis, sickle cell anemia, fragile X syndrome, Huntington's disease, and muscular dystrophy. It provides details on the genetics, symptoms, inheritance patterns, and impact of each disorder. References are also included at the end related to catastrophic antiphospholipid syndrome.
Mitochondrial Inheritance in Man
This document discusses mitochondrial inheritance in humans. It begins by describing mitochondria and their role in cellular respiration and ATP synthesis. Mitochondrial DNA is circular and encodes for proteins, tRNAs and rRNAs. Mutations can occur in mtDNA and be heteroplasmic. Mitochondrial disorders are maternally inherited and can result from mutations in mtDNA or nuclear DNA. Common syndromes include MELAS, MERRF and LHON. Diagnosis involves family history, clinical evaluation, biochemical testing, muscle biopsy and genetic testing. Treatment focuses on symptom management and supplementation. Mitochondrial defects can impact female and male fertility by reducing ATP production necessary for processes like oocyte maturation and sperm motility. New therapies involving
Hedgehog Pathway
The Hedgehog pathway was discovered in fruit fly (Drosophila) and is conserved in vertebrates (including humans)
The Hedgehog pathway is involved in cell growth and differentiation to control organ formation during embryonic development.
Hedgehog signalling regulates embryonic development, ensuring that tissues reach their correct size and location, maintaining tissue polarity and cellular content.
In the skin, the Hedgehog pathway is critical for regulating hair follicle and sebaceous gland development.
Germline mutations in components of the Hedgehog signalling pathway results in a number of developmental abnormalities.
Hedgehog signalling normally remains inactive in most adult tissues
Lecture.9 Gene Therapy: An Introduction
Qurat-ul-Ain, who holds a B. Pharm, M. Phil, and Ph.D., teaches the 9th lecture on basic processes of molecular biology and introduction to molecular medicine and gene therapy. She is a visiting assistant professor at the Department of Physical Therapy, Faculty of Health & Medical Sciences at Hamdard University in Karachi, Pakistan and an assistant professor at the Department of Pharmaceutical Chemistry, Faculty of Pharmacy at Hamdard University in Karachi, Pakistan. The document provides her contact information.
Lecture.8 Basic Molecular Biology Techniques
This document appears to be a series of lecture slides presented by Qurat-ul-Ain on basic processes of molecular biology. The slides cover topics including cell-based DNA cloning, nucleic acid hybridization assays, PCR, DNA sequencing, in vitro mutagenesis, physical mapping, and thank attendees. The lectures were presented in six parts and focused on fundamental molecular biology techniques.
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Mitochondrial disorders overview
- Mitochondrial diseases are caused by mutations in mitochondrial DNA (mtDNA) and can affect multiple organ systems. They are characterized by failure of mitochondria to produce sufficient energy for cells.
- mtDNA is inherited solely from mothers and can be heteroplasmic, containing both mutated and normal mtDNA. This explains varying severity between mothers and children.
- The patient described presented with encephalopathy, lactic acidosis, strokes and other multi-system involvement consistent with a mitochondrial disorder. Whole mitochondrial genome sequencing detected a mtDNA deletion of unknown extent/genes involved.
- When evaluating for possible mitochondrial disease, consider if a patient has an unexplained combination of features like lactic acidosis,
Gene medicine by kk sahu sir
INTRODUCTION
DNA VACCINES
GENE THERAPY
TIME LINE OF DEVELOPING GENE THERAPY
GENE THERAPY STRATEGIES
TECHNOLOGY OF CLASSICAL GENE THERAPY
PRINCIPLES OF GENE TRANSFER
VECTORS
VIRAL VECTORS
NON-VIRAL VECTORS
APPLICATIONS OF GENE THERAPY
ETHICAL IMPLICATIONS
THE FUTURE
CONCLUSION
REFERENCES
Regulation by Wnt Signaling
The Wnt cascade has emerged as a critical regulator of stem cells. In many tissues, activation of Wnt signaling has also been found to be associated with cancer. Understanding the regulation by Wnt signaling may serve as a paradigm for understanding the dual nature of self-renewal signals.
Genetics of mitochondrial diseases
Dr. Gayathri N. chaired a presentation by Dr. Govindaraju C. on mitochondrial genetics and diseases. The 3-sentence summary is:
The presentation covered the basics of mitochondrial genetics including structure, inheritance, and respiratory chain; it classified mitochondrial diseases into those caused by nuclear DNA and mtDNA mutations. Mitochondrial diseases can affect multiple organ systems and be caused by mutations in respiratory chain complexes or assembly factors, with phenotypes including Leigh syndrome, cardiomyopathy, leukodystrophy, and optic atrophy.
Stem cell therapy in neurological disorder
Stem cell therapy shows promise for treating neurological diseases. Various stem cell sources like embryonic stem cells, induced pluripotent stem cells, and adult neural stem cells can differentiate into neural cells and may be able to replace damaged or dead cells. Clinical trials have been conducted for conditions like Parkinson's disease and stroke with some patients showing improvements, but larger trials are still needed to confirm efficacy and safety. Challenges remain in ensuring stem cells engraft and properly differentiate in the brain.
Oncogene and tumor suppressor gene
Oncogene And Tumor Suppressor Gene
The document discusses oncogenes and tumor suppressor genes. It defines proto-oncogenes as genes involved in cell growth that can become activated oncogenes through mutations. Oncogenes are classified into five groups. Tumor suppressor genes normally inhibit tumor formation but mutations inactivate this function in a two-hit model. Examples discussed include HER2/neu, Ras, Myc, Rb, p53, BRCA1, BRCA2, and APC.
Mitochondrial Disorder
Mitochondrial diseases are caused by defects in the mitochondria or mitochondrial genome. The mitochondria produce energy in cells through oxidative phosphorylation and have important roles in calcium regulation, apoptosis, and reactive oxygen species generation. Mitochondrial DNA mutations can cause a variety of clinical syndromes affecting high-energy tissues like brain, muscle, heart. Common syndromes include MELAS, MERRF, and Leigh syndrome. Diagnosis involves assessing clinical features, blood/CSF lactate levels, muscle biopsy showing ragged red fibers, and genetic testing. Treatment focuses on managing symptoms while avoiding metabolic stress.
Mitochondrial disorders
A mitochondrion (singular of mitochondria) is part of every cell in the body that contains genetic material.
Mitochondria are responsible for processing oxygen and converting substances from the foods we eat into energy for essential cell functions.
The mitochondria of the zygote come from the oocyte, that is, from the mother and almost never from the sperm, form of transmission is called maternal inheritance
Which mitochondrial gene is mutated.
The extent of replicative segregation of the mutant mitochondrial genome during the early stages of embryonic development.
The abundance of the mutant mitochondrial gene in a particular tissue.
The threshold level of mutant mitochondrial DNA required in a tissue before an abnormality is evident clinically
Mitochondrial disease affects tissues most highly dependent on ATP production
*Nerves
*Muscles
Endocrine
Kidney
Low energy-requiring tissues are rarely directly affected, but may be secondarily
Lung
Connective tissue
Symptoms can be intermittent
Increased energy demand (illness, exercise)
Decreased energy supply (fasting)
Common feature
myoclonus epilepsy, deafness, blindness, anemia, diabetes, seizures and loss of cerebral blood supply (stroke).
Myoclonic epilepsy and ragged-red fiber disease (MERRF)
MERRF is a member of a group of disorders called mitochondrial encephalomyopathies that feature mitochondrial defects with altered brain and muscle functions.
The term “ragged red fibers” refers to large clumps of abnormal mitochondria that accumulate mostly in muscle cells and are stained red by a dye that is specific for complex II of the electron transport chain.
rare, maternally inherited, heteroplasmic, (point mutation in tRNA lysine gene)
Mutation is MTTK*MERRF8344G.
MT means mitochondrial gene is mutated
T means transfer RNA gene
K means the single-letter amino acid designation for lysine
MERRF means the clinical features
8344G means the mutant nucleotide is guanine (G) at nucleotide position 8344
If 90% of the mitochondria in nerve and muscle cells carry the MTTK*MERRF8344G mutation, then the defining symptoms of MERRF are present.
Maternally inherited mitochondrial disease
The MTTL1*MELAS3243G mutation accounts for more than 80% of the cases of MELAS.
This base substitution is in one of the two mitochondrial transfer RNALeu genes.
the A3243G mutation occurs in thetRNALeu(UUR) gene
When this mutation is present in ≥90% of the mitochondrial DNA of muscle tissue, there is an increased likelihood of recurrent strokes, dementia, epilepsy, and ataxia.
When heteroplasmy for the A3243G mutation
is ~40% to 50%, chronic progressive external ophthalmoplegia (CPEO), myopathy, and deafness are likely to occur.
Other MELAS mutations occur at sites 3252, 3271, and 3291 within the tRNALeu(UUR) gene and in the mitochondrial tRNAVal (MTTV) and COX III (MTCO3) genes.
Reduced activities in Complexes I and IV are established
Huntington
Huntington's disease is a neurodegenerative genetic disorder that causes the progressive breakdown of nerve cells in the brain, especially in the basal ganglia. It affects movement, cognition, and psychiatric functions and is caused by a defective gene inherited from a parent. Symptoms typically appear between ages 30-50 and include involuntary movements, cognitive decline, and psychiatric issues like depression. While there is no cure, treatment aims to reduce symptoms and complications through medications, speech/occupational/physical therapy, and supportive care.
STEM CELL CULTURE
This document discusses stem cell culture and provides definitions, classifications, and methods for culturing different types of stem cells. It summarizes the history of stem cell research from 1981 to present. It describes embryonic stem cells, adult stem cells including bone marrow and umbilical cord stem cells. Methods are outlined for isolating and culturing stem cells from bone marrow and umbilical cord. Advantages and disadvantages of different stem cell sources are compared.
Epigenetics
Epigenetics involves heritable changes in gene expression that are not caused by changes in the underlying DNA sequence. These changes are caused by mechanisms such as chromatin remodeling and DNA methylation. While genetics is determined by the DNA sequence, epigenetics influences which genes are expressed through modifications to histone proteins and DNA. These epigenetic modifications play important roles in development and can cause diseases if disrupted, such as imprinting disorders. Significant research is being conducted worldwide at top institutions like Johns Hopkins University to better understand epigenetics and its effects.
Epigenetics
This presentation on Epigenetics is most advanced and evidence based one. Its Very helpful for Genetics students and research fellows, Reproductive Medicine specialist, Reproductive Biologist, Infertility practitioners
Epigenetics
This document defines epigenetics as heritable changes in gene expression that are not caused by changes in DNA sequence. It discusses genomic imprinting, where alleles from the father and mother are expressed differently. Genomic imprinting is explained by the parental conflict theory, which posits that genes have evolved conflicting interests in how much they provision offspring depending on whether they are inherited from the father or mother. Imprinting marks on DNA are established differently depending on the parent of origin and can be erased in germ line cells, but reestablished in offspring. Problems can occur if imprinting marks are defective or the wrong parental alleles are inherited.
Human genome project 1
The document discusses the history and goals of the Human Genome Project, which began in 1990 with the aim of identifying all human genes and determining the sequence of DNA base pairs. Some key goals were to map all genes, determine DNA sequences, and address ethical issues. The project was completed earlier than expected in 2003 and has led to over 1,800 disease genes being discovered and many medical benefits like new diagnostic tests.
Stem cell therapy
Stem cell therapy holds promise for treating many incurable diseases by replacing damaged cells. There are various types of stem cells including embryonic, adult, and induced pluripotent stem cells. While embryonic stem cells can differentiate into any cell type, their use is controversial due to requiring embryo destruction. Alternative sources like adult stem cells and iPS cells do not have the same ethical issues but may have limitations. Stem cell research faces challenges like preventing immune rejection and tumor formation but continues to advance regenerative medicine.
Epigenetics
C.H. Waddington coined the term "epigenetics" in the 1940s to describe how environmental influences can affect gene expression and phenotypic traits. Epigenetics is the study of reversible modifications to DNA and chromatin that regulate gene expression in response to environmental factors without changing DNA sequences. The epigenome refers to the unique patterns of gene expression established in different cell types through DNA methylation, histone modifications, and noncoding RNAs. These epigenetic marks can be transmitted from parent cells to daughter cells and between generations.
Neuronal stem cellfi
This document provides an overview of neural stem cells (NSCs). It discusses the location and development of NSCs in the central nervous system. Key cell signaling pathways that regulate NSCs, such as Notch and WNT, are described. Common markers used to identify NSCs are discussed, including Nestin, Sox2, Musashi-1, Pax6, and CD133. Factors that affect the growth and multiplication of NSCs, such as growth factors EGF and FGF, are outlined. Methods for isolating and culturing NSCs are presented. Finally, potential therapeutic applications of NSCs are reviewed, along with some current clinical trials utilizing NSCs.
Single gene disorders
This document discusses several single-gene disorders including cystic fibrosis, sickle cell anemia, fragile X syndrome, Huntington's disease, and muscular dystrophy. It provides details on the genetics, symptoms, inheritance patterns, and impact of each disorder. References are also included at the end related to catastrophic antiphospholipid syndrome.
Mitochondrial Inheritance in Man
This document discusses mitochondrial inheritance in humans. It begins by describing mitochondria and their role in cellular respiration and ATP synthesis. Mitochondrial DNA is circular and encodes for proteins, tRNAs and rRNAs. Mutations can occur in mtDNA and be heteroplasmic. Mitochondrial disorders are maternally inherited and can result from mutations in mtDNA or nuclear DNA. Common syndromes include MELAS, MERRF and LHON. Diagnosis involves family history, clinical evaluation, biochemical testing, muscle biopsy and genetic testing. Treatment focuses on symptom management and supplementation. Mitochondrial defects can impact female and male fertility by reducing ATP production necessary for processes like oocyte maturation and sperm motility. New therapies involving
Hedgehog Pathway
The Hedgehog pathway was discovered in fruit fly (Drosophila) and is conserved in vertebrates (including humans)
The Hedgehog pathway is involved in cell growth and differentiation to control organ formation during embryonic development.
Hedgehog signalling regulates embryonic development, ensuring that tissues reach their correct size and location, maintaining tissue polarity and cellular content.
In the skin, the Hedgehog pathway is critical for regulating hair follicle and sebaceous gland development.
Germline mutations in components of the Hedgehog signalling pathway results in a number of developmental abnormalities.
Hedgehog signalling normally remains inactive in most adult tissues
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Isaac Karimi is an Iranian candidate associate professor with expertise in enzymology, ecophysiology, ethnomedicine, translational research, and biomathematics. He received his DVM and DVSc degrees from Iranian universities and conducted research at universities in Mexico and the United States. Karimi has taught over 30 courses in subjects including physiology, biochemistry, and neuroscience at Iranian universities. He has established several research laboratories and is skilled in various experimental techniques. Karimi is a member of international scientific societies and reviews manuscripts for peer-reviewed journals.
Clinical pharmacology hormonal disorders
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A Textbook of Clinical-Pharmacy, Essential concepts and skills
This document provides an overview of the textbook "A Textbook of Clinical Pharmacy Practice: Essential Concepts and Skills". The textbook is in its second edition and aims to teach the essential concepts and skills of clinical pharmacy practice. It contains 30 chapters contributed by experts in clinical pharmacy from India and other countries. The chapters cover topics such as community and hospital pharmacy practice, communication skills, medication adherence, pharmacovigilance, clinical skills like ward rounds and medication reviews, and specialized topics such as geriatric pharmacy and pharmacoeconomics. The textbook is intended to support the teaching of clinical pharmacy to pharmacy students and practicing pharmacists.
Radiolabeling methods for 5 fluorouracil (5-fu) with technetium-99m for precl...
Radiolabeling methods for 5 fluorouracil (5-fu) with technetium-99m for precl...SSR Institute of International Journal of Life Sciences
ABSTRACT- Background: 5-Fluorouracil (5-FU) is a well known anti metabolites and extensively used in chemotherapy. The search of target specific radiopharmaceutical is always on in field of radiopharmaceutical and diagnostic nuclear imaging. In this study we have developed the radiolabling methodology for the 5-FU with Technetium-99m for preclinical nuclear imaging evaluation of 99mTc- labeled 5-FU.
Material and Methods: We have used radio pharmacy lab and its equipments of Bhagwan Mahaveer Cancer Hospital & Research Centre (BMCHRC), Jaipur, Rajasthan, India. We have used simple basic radiochemical reactions for the radiolabeling of the 5-FU. 99mTc pertechnetate, an elute from 99Mo-99mTc generator used for tagging. A series of high grade and analytical chemical were used and a few from outside without further purification e.g. L-Cysteine Monohydrae acid, SnCl2.2.H2O, Normal Saline, Distilled water, pH meter. SnCl2.2H2O was used for the reduction reaction. Post radiolableing paper and ITL chromatography techniques used for the standardization and characterization of the labeled radiopharmaceutical.
Results: We have observed >95.66% radiolabeling efficiency of 5-Fluorouracil (5-FU) with Technetium-99m by the paper chromatography (PC) and instant thin layer chromatography (ITLC) radiochemical efficiency labelling techniques.
Conclusion: As per our observation and study 99mTc-5-FU has a potential to be of becoming a useful tool for the Nuclear Imaging of solid tumor. The labeled drug can be used for the gamma imaging after conducting further clinical trials on animal and human.
Key-words- Radiolabeling, Preclinical Nuclear Imaging (PNI), 5-Fluorouracil (5-FU), Paper Chromatography (PC) and Instant Thin Layer Chromatography (ITLC)
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The document provides information about the Faculty of Pharmacy at the University of Central Punjab in Lahore, Pakistan. It includes a welcome message from the Dean, Dr. Mehtab Ahmad Khan, highlighting the faculty's world-class education and research. It then lists the leadership team of 32 professors and lecturers, most of whom have PhDs. It outlines the learning methods used, including lectures, tutorials, presentations and clinical practical experience. Finally, it lists the 11 laboratories available to students.
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Robert C. Shepard has extensive experience in cancer research and clinical oncology spanning over 40 years. He received his MD from Duke University and has held academic and clinical positions at several prestigious institutions. Currently, he works as a consultant in oncology drug development and clinical trials. He has led numerous clinical trials for both pharmaceutical and biotech companies and has published extensively in peer-reviewed journals. His expertise includes all phases of clinical trial design and implementation.
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This curriculum vitae summarizes the qualifications of Mohanad A. Al-Bayati, an Assistant Professor of Physiology and Pharmacology at the University of Baghdad. It outlines his education, including a BVM&S, MSc in Physiology, and PhD in Pharmacology and Toxicology. It also lists his academic positions, teaching experience, research interests in reproductive physiology and the nitric oxide system, publications, and thesis supervision of 64 students.
Atiqur_Rahman_B Pharm_Resume
Atiqur Rahman is seeking an excellent position where he can utilize his skills. He has a Bachelor of Pharmacy degree from PTU with a project on transmucosal drug delivery systems like buccal films. During his industrial training, he learned about batch manufacturing processes like mixing raw materials and tablet compression. He has participated in seminars and conferences related to pharmacy and biotechnology. His strengths include working hard, having an analytical mind, and being a fast learner.
1
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This document presents information on phenolic compounds and tannins from the perspective of pharmacognosy and its research areas. It discusses the purposes of pharmacognosy study including plant identification, bioactivity assessment, drug discovery, and development. Tannins are described as polyphenolic substances found in many plants that are soluble in alkalis and organic solvents. True and pseudo tannins are classified. Examples of plants that contain tannins are provided, including white catechu, black catechu, and nutgall. Specific compounds in these plants like catechins, quercetin, and gallotannic acid are discussed. The neurobiological effects of gallic acid and pharmacological activities of quCANCER TREATMENT: ROLE OF EGFR, TOPOISOMERASE AND TUBULIN
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Curative
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Adjuvant
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Targeted cancer chemotherapy: Acts on cellular targets.
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INFORMATION OF FACULTY REQUIRED FOR THE UNIVERSITYN WEB SITE
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A Textbook of Clinical-Pharmacy, Essential concepts and skills
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Radiolabeling methods for 5 fluorouracil (5-fu) with technetium-99m for precl...
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Lecture.10 Gene Therapy for Neurological Disorders: Introduction
- 1. MOLECULAR BIOLOGY & GENETICS Basic Processes of Molecular Biology Gene Therapy for Neurological Disorders: Introduction 10th Lecture Qurat-ul-Ain, B. Pharm., M. Phil., Ph.D., Visiting Assistant Professor Department of Physical Therapy, Faculty of Health& Medical Sciences, Hamdard University, Karachi, Pakistan Assistant Professor Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hamdard University, Karachi, Pakistan. Qurat-ul-Ain, B. Pharm., M. Phil., Ph.D., qurat.fophu@yahoo.com
- 3. Qurat-ul-Ain, B. Pharm., M. Phil., Ph.D., qurat.fophu@yahoo.com
- 4. Qurat-ul-Ain, B. Pharm., M. Phil., Ph.D., qurat.fophu@yahoo.com
- 5. Qurat-ul-Ain, B. Pharm., M. Phil., Ph.D., qurat.fophu@yahoo.com
- 6. Qurat-ul-Ain, B. Pharm., M. Phil., Ph.D., qurat.fophu@yahoo.com
- 7. Qurat-ul-Ain, B. Pharm., M. Phil., Ph.D., qurat.fophu@yahoo.com
- 8. Qurat-ul-Ain, B. Pharm., M. Phil., Ph.D., qurat.fophu@yahoo.com
- 9. Qurat-ul-Ain, B. Pharm., M. Phil., Ph.D., qurat.fophu@yahoo.com
- 10. Fight or Flight Restores The Body To A Calm Qurat-ul-Ain, B. Pharm., M. Phil., Ph.D., qurat.fophu@yahoo.com
- 11. Qurat-ul-Ain, B. Pharm., M. Phil., Ph.D., qurat.fophu@yahoo.com
- 12. Qurat-ul-Ain, B. Pharm., M. Phil., Ph.D., qurat.fophu@yahoo.com
- 13. Qurat-ul-Ain, B. Pharm., M. Phil., Ph.D., qurat.fophu@yahoo.com
- 14. Qurat-ul-Ain, B. Pharm., M. Phil., Ph.D., qurat.fophu@yahoo.com
- 15. WHAT IS A BRAIN TUMOR? 120 Types Qurat-ul-Ain, B. Pharm., M. Phil., Ph.D., qurat.fophu@yahoo.com
- 16. Qurat-ul-Ain, B. Pharm., M. Phil., Ph.D., qurat.fophu@yahoo.com
- 17. Qurat-ul-Ain, B. Pharm., M. Phil., Ph.D., qurat.fophu@yahoo.com
- 18. Glioblastoma (GBM) is a brain tumor of neuroectodermal origin. It is a second most common primary brain neoplasm and the most common from malignant brain tumors. Glioblastoma Qurat-ul-Ain, B. Pharm., M. Phil., Ph.D., qurat.fophu@yahoo.com
- 19. Genes involved in genesis of primary, secondary, and pediatric glioblastoma. *Gain of function through amplification or mutation; ǂhomozygous deletion or mutation. Qurat-ul-Ain, B. Pharm., M. Phil., Ph.D., qurat.fophu@yahoo.com
- 20. Thank You………………
- 33. Thank YOU………….