This document discusses advances in gene therapy. It begins by explaining what gene therapy is and provides examples of how it has been used to treat children with severe immune deficiencies who previously had to live in protective bubbles. While bone marrow transplants can cure these conditions, they often fail due to graft-versus-host disease. Gene therapy offers advantages over bone marrow transplants by using a patient's own cells with corrected genes, avoiding this complication. The document outlines the process of doing gene therapy outside the body by inserting genes into viruses to deliver them to patients' cells. It notes some of the early successes and challenges of gene therapy clinical trials.
Gene therapy is an experimental technique that uses genes to treat disease by inserting genes into patients' cells instead of using drugs or surgery. Recent research has shown promising advances in gene therapy to treat various diseases. However, gene therapy still faces technical challenges such as safely delivering genes to target cells and tissues, potential immune responses, and difficulty treating complex multigenic disorders. While still experimental, gene therapy offers hope for treating currently incurable conditions.
Genetic polymorphisms can affect how individuals metabolize and respond to drugs. The document discusses how single nucleotide polymorphisms (SNPs) in genes encoding drug-metabolizing enzymes like the cytochrome P450 system can result in poor, intermediate, normal, extensive, or ultra-rapid metabolizers. This genetic variation impacts the metabolism of many drugs and can influence their effects as well as drug interactions. The cytochrome P450 2C19 enzyme, which is important in metabolizing diazepam, shows polymorphisms that lead to different drug responses and side effects between ethnic populations. Understanding these pharmacogenomic factors is important for optimizing drug therapy.
ICH guidelines provide standards for toxicity studies to ensure safe, effective, and high quality pharmaceutical products. Guideline S3A deals with conducting toxicity studies and quantifying exposure. General principles include quantifying exposure levels in different species and sexes using plasma concentration or area under the curve. Toxicokinetic studies should be performed to determine metabolite levels and justify dose levels. Reporting should include detailed toxicokinetic data and evaluation. Toxicokinetics are assessed in various toxicity studies including single dose studies, repeated dose studies, genotoxicity studies, carcinogenicity studies, and reproductive toxicity studies.
This document discusses gene mapping and sequencing. It begins by defining genomics and genetic markers such as RFLP, SSLP, and SNP that are used to track inheritance. Gene mapping involves determining the locus and distance between genes on chromosomes, which is important for diagnosing genetic diseases. There are two main types of gene mapping: linkage mapping which measures recombination frequency to determine if genes are linked, and physical mapping which precisely locates DNA sequences on chromosomes using techniques like fluorescence in situ hybridization. The document also discusses methods for gene sequencing, including Sanger sequencing and Maxam-Gilbert sequencing, as well as newer techniques like shotgun sequencing and Illumina sequencing.
This document discusses gene cloning. Gene cloning involves making multiple copies of a single gene. It has basic steps including constructing recombinant DNA, transporting it to a host cell, multiplying the recombinant DNA, and dividing the host cell to produce numerous clones. Plasmids are commonly used as cloning vectors because they can replicate in host cells. Key components of cloning vectors include the replication origin, antibiotic resistance genes like ampR for selection, and reporter genes like lacZ. The lacZ gene is interrupted by the inserted gene of interest, allowing blue-white screening to identify successful clones. Applications of gene cloning discussed are producing the first genetically modified Flavr Savr tomato and creating Bt plants resistant to pests.
Pharmacogenomics is the branch of biochemistry in which study how an individual’s genetic inheritance affects the body response to drug. Pharmacogenomics is the intersection of genetics and pharmaceutical industry.
In this presentation a brief note is given about what is pharmacogenomics. Why different drugs work differently in different people. today pharmacogenomics, future of pharmacogenomics. also describe the future of pharmacogenomics. challenges which have to pharmacogenomics.
Gene mapping and cloning of disease geneDineshk117
This document provides an overview of gene mapping and cloning of disease genes. It discusses genetic mapping and physical mapping techniques used to locate genes on chromosomes, including linkage mapping using polymorphic DNA markers like RFLPs, SSLPs, and SNPs. The document also describes cloning a disease gene, which involves constructing a recombinant DNA molecule containing the gene, multiplying the recombinant DNA in host cells, and obtaining numerous clones with the gene of interest. PCR and other molecular techniques are important tools in gene cloning and mapping diseases at the DNA level.
Gene therapy is an experimental technique that uses genes to treat disease by inserting genes into patients' cells instead of using drugs or surgery. Recent research has shown promising advances in gene therapy to treat various diseases. However, gene therapy still faces technical challenges such as safely delivering genes to target cells and tissues, potential immune responses, and difficulty treating complex multigenic disorders. While still experimental, gene therapy offers hope for treating currently incurable conditions.
Genetic polymorphisms can affect how individuals metabolize and respond to drugs. The document discusses how single nucleotide polymorphisms (SNPs) in genes encoding drug-metabolizing enzymes like the cytochrome P450 system can result in poor, intermediate, normal, extensive, or ultra-rapid metabolizers. This genetic variation impacts the metabolism of many drugs and can influence their effects as well as drug interactions. The cytochrome P450 2C19 enzyme, which is important in metabolizing diazepam, shows polymorphisms that lead to different drug responses and side effects between ethnic populations. Understanding these pharmacogenomic factors is important for optimizing drug therapy.
ICH guidelines provide standards for toxicity studies to ensure safe, effective, and high quality pharmaceutical products. Guideline S3A deals with conducting toxicity studies and quantifying exposure. General principles include quantifying exposure levels in different species and sexes using plasma concentration or area under the curve. Toxicokinetic studies should be performed to determine metabolite levels and justify dose levels. Reporting should include detailed toxicokinetic data and evaluation. Toxicokinetics are assessed in various toxicity studies including single dose studies, repeated dose studies, genotoxicity studies, carcinogenicity studies, and reproductive toxicity studies.
This document discusses gene mapping and sequencing. It begins by defining genomics and genetic markers such as RFLP, SSLP, and SNP that are used to track inheritance. Gene mapping involves determining the locus and distance between genes on chromosomes, which is important for diagnosing genetic diseases. There are two main types of gene mapping: linkage mapping which measures recombination frequency to determine if genes are linked, and physical mapping which precisely locates DNA sequences on chromosomes using techniques like fluorescence in situ hybridization. The document also discusses methods for gene sequencing, including Sanger sequencing and Maxam-Gilbert sequencing, as well as newer techniques like shotgun sequencing and Illumina sequencing.
This document discusses gene cloning. Gene cloning involves making multiple copies of a single gene. It has basic steps including constructing recombinant DNA, transporting it to a host cell, multiplying the recombinant DNA, and dividing the host cell to produce numerous clones. Plasmids are commonly used as cloning vectors because they can replicate in host cells. Key components of cloning vectors include the replication origin, antibiotic resistance genes like ampR for selection, and reporter genes like lacZ. The lacZ gene is interrupted by the inserted gene of interest, allowing blue-white screening to identify successful clones. Applications of gene cloning discussed are producing the first genetically modified Flavr Savr tomato and creating Bt plants resistant to pests.
Pharmacogenomics is the branch of biochemistry in which study how an individual’s genetic inheritance affects the body response to drug. Pharmacogenomics is the intersection of genetics and pharmaceutical industry.
In this presentation a brief note is given about what is pharmacogenomics. Why different drugs work differently in different people. today pharmacogenomics, future of pharmacogenomics. also describe the future of pharmacogenomics. challenges which have to pharmacogenomics.
Gene mapping and cloning of disease geneDineshk117
This document provides an overview of gene mapping and cloning of disease genes. It discusses genetic mapping and physical mapping techniques used to locate genes on chromosomes, including linkage mapping using polymorphic DNA markers like RFLPs, SSLPs, and SNPs. The document also describes cloning a disease gene, which involves constructing a recombinant DNA molecule containing the gene, multiplying the recombinant DNA in host cells, and obtaining numerous clones with the gene of interest. PCR and other molecular techniques are important tools in gene cloning and mapping diseases at the DNA level.
This document discusses in silico drug design. It begins by defining drugs and the drug design process. Drug molecules should be small, complementary in shape to the target, and oppositely charged. In silico drug design uses computer simulations to identify drug target molecules. There are ligand-based and structure-based approaches. Key steps are selecting a disease and target, target validation, selecting ligands, applying scoring functions, lead optimization, and preclinical/clinical development. The goal is to eliminate compounds that may cause side effects or drug interactions. In silico methods help integrate new technologies with traditional medicinal chemistry experience to discover safe and effective drug leads.
This document discusses pharmacogenomics and how genetic differences can influence individual responses to drugs. It provides examples of how single nucleotide polymorphisms and other genetic variations can affect drug targets, metabolizing enzymes, transporters, and ultimately impact pharmacokinetics, pharmacodynamics, efficacy, and toxicity. Specifically, it examines cases of polymorphisms in cytochrome P450 drug metabolizing enzymes like CYP2C9, CYP2C19, and CYP2D6 that can lead to differences in drug metabolism and clearance between fast, normal, and poor metabolizers. The goals of pharmacogenomics are to maximize drug efficacy, minimize toxicity, and aid precision medicine by predicting who will respond to certain drugs. Widespread application
The document discusses pharmacogenomics and how genetic variations can affect individual responses to drugs. It describes how pharmacogenomics examines genomic loci and biological pathways to determine drug variability. It also discusses pharmacogenetics which focuses on single gene variants. The document outlines some merits of pharmacogenomics like improving drug safety and personalized treatment. It then discusses various scenarios on how genetic polymorphisms can impact different drug metabolism pathways. Finally, it examines how specific genetic variations in drug metabolizing enzymes and transporters can influence drug pharmacokinetics and potential adverse effects.
Role of Target Identification and Target Validation in Drug Discovery ProcessPallavi Duggal
Target identification and Validation tells about the how target is neccesary for new drug discovery and its development to reach into market for rare diseases.
- Pharmacogenomics deals with how genetic variations influence individual responses to drugs in terms of efficacy and toxicity. It aims to identify individuals who are more or less likely to respond to drugs or require altered doses.
- Pharmacogenetics studies variations in targeted genes or related genes, while pharmacogenomics uses genetic information to guide individualized drug and dose choice.
- Genetic polymorphisms like SNPs can result in different amino acids, protein changes, or no effect. They influence drug metabolism and response.
- Pharmacogenomics offers advantages like personalized medicine but faces barriers like complexity, education needs, and drug company incentives. It is being applied in various stages of clinical trials from target identification to dosing.
This document discusses drug discovery and the process of identifying potential new drug targets. It outlines the need for drug discovery to develop treatments for diseases without existing therapies. The key steps in drug discovery include target identification using genomics and proteomics to study the genome and map protein-protein interactions, as well as target validation using techniques like RNA interference and transgenic animal models. Bioinformatics plays an important role in analyzing large datasets to aid in drug target discovery and validation.
Proteomics is the study of proteins, including their composition, structure, function and interactions. It can be used to identify protein-protein interactions and complexes. Expression proteomics analyzes protein quantification and how levels are controlled. Proteomics has applications in new drug discovery by identifying proteins involved in diseases and developing drugs that target or inactivate those proteins. Genomics studies genomes and all their genes, DNA, and proteomes. It has applications in medicine, microbiology, forensics, agriculture and more. Metabolomics studies small molecule metabolites within cells and biofluids and their interactions, with applications in pharmacology, toxicology and functional genomics. Nutrigenomics examines how food constituents affect gene expression and identifies
This document summarizes a seminar on pharmacogenomics presented by Mr. Madhan Mohan Elsani. Pharmacogenomics is the study of how genes influence individual responses to drugs. Understanding genetic variations between individuals can help explain differences in drug efficacy and risk of adverse reactions. Single nucleotide polymorphisms (SNPs) are variations in DNA sequences that can impact how the body processes and metabolizes drugs. Pharmacogenomic testing can help optimize drug selection and dosing for individual patients based on their genetic makeup. This could improve drug safety and reduce adverse reactions.
Introduction to Immunotherapeutics
Cell mediated & humoral immunity, Immunosuppressants, Immunostimulants
Presented by
G. Sai Swetha
Department of Pharmacology
Genomics, proteomics, and bioinformatics are important fields that help advance drug development. Genomics studies entire genomes and can identify disease-associated genes. Proteomics identifies the proteins expressed in a sample and how they differ between healthy and diseased tissues. Bioinformatics uses computers to store and analyze biochemical and biological data, especially related to genomics. These fields help discover new drug targets, validate existing targets, select drug candidates, study mechanisms of action and toxicity. Integrating omics data from genomics to proteomics provides a more comprehensive understanding of biological systems compared to individual fields alone.
1. Gene mapping is the process of establishing the locations of genes on chromosomes, while gene sequencing determines the order of nucleotides within genes.
2. There are two main types of genome mapping - genetic mapping, which provides evidence that a disease is linked to genes, and physical mapping, which constructs maps by characterizing and assembling DNA fragments.
3. Restriction mapping uses restriction enzymes to cut DNA at specific sites, allowing genes to be mapped based on the resulting fragment sizes.
Antisense oligonucleotide therapy is a pharmacological approach that uses synthetic genetic material to inhibit protein translation by binding to mRNA. It works by blocking ribosomes, activating RNase enzymes, or forming triplex structures. Advantages include rapid manufacturing and potential for enhanced targeting. Limitations include short half-lives and difficulty directing to specific cells. Over 50 antisense compounds are in clinical trials for various diseases. The future of antisense-based therapies looks promising as more companies develop applications.
siRNA and miRNA both regulate gene expression, but through different mechanisms. siRNA targets specific gene sequences, while a single miRNA can regulate many genes. siRNA is found in plants, fungi, and insects but not mammals, which have other antiviral responses. miRNA are small non-coding RNAs around 22 nucleotides long that bind to mRNA to repress translation or promote degradation. They play important roles in development, physiology, and disease when their expression is dysregulated.
The document is a presentation by Manju Jakhar, who is an M.Pharm student in Pharmacology in their 2nd semester. Manju Jakhar will be presenting on their area of study and current level of education. The presentation provides basic identifying information about the presenter.
1. siRNA and miRNA are types of non-coding RNAs that play important roles in post-transcriptional gene regulation. siRNA induces gene silencing through RNA interference, while miRNA binds to target mRNAs to inhibit translation.
2. Both siRNA and miRNA have shown promise in developing therapies for diseases like cancer, asthma, neurodegenerative disorders, and viral infections by silencing genes involved in disease pathways. Delivery methods continue to be improved to enhance their therapeutic potential.
3. The key differences between siRNA and miRNA are their biogenesis, targeting specificity, and mechanisms of gene regulation. siRNA is synthesized from long double-stranded RNA and can perfectly complement target mRNAs, while miRNA originates from
This document provides an overview of pharmacogenetics and discusses:
1. Pharmacogenetics is the study of how genetic factors influence individual responses to drugs. It considers both environmental and genetic factors that impact drug metabolism and effects.
2. Key concepts include how genetic polymorphisms affect drug metabolizing enzymes and transporters, leading to variability in drug efficacy and risk of adverse reactions between individuals.
3. The field has progressed from early discoveries of genetic disorders affecting drug response to now understanding the effects of common gene variants, with the goal of personalized medicine to optimize drug therapy for each patient.
Genetic variation in drug transportersDeepak Kumar
This document discusses various transporter proteins involved in drug transport. It describes two main superfamilies - ATP-binding cassette (ABC) transporters and Solute-carrier (SLC) transporters. ABC transporters such as P-glycoprotein, MRP1, and BCRP act as efflux pumps and influence the bioavailability and toxicity of various drugs like irinotecan. Genetic variants in these transporters affect individual responses to drugs. SLC transporters import substances and influence drug absorption and distribution. Variations in transporter expression across tissues and individuals impact drug pharmacokinetics and treatment outcomes.
Gene therapy was once considered imaginary but has since made progress, including the first approved gene therapy treatment in 1990 for a girl with ADA deficiency. Gene therapy involves inserting genes into a person's cells to treat or prevent disease by replacing missing or defective genes. It can be done through viral or non-viral vectors and ex vivo or in vivo approaches. Recent advances include using gene therapy to regenerate heart cells in mice, MRI-guided brain cancer gene therapy, and stem cell gene therapy showing promise for treating neurological diseases. However, gene therapy still faces challenges like short-lived effects, immune responses, and difficulties treating multi-gene disorders.
Pharmacogenomics- a step to personalized medicinesApusi Chowdhury
Pharmacogenomics aims to optimize drug therapy based on a patient's genotype to maximize efficacy and minimize adverse effects. It involves studying how genetic factors influence individual responses to drugs in terms of absorption, distribution, metabolism, and excretion. Genetic polymorphisms like SNPs that occur in over 1% of the population can impact a drug's effects. Pharmacogenomic testing identifies biomarkers related to drug metabolism and targets to determine effective treatments and dosages for patients. While it holds promise for improving drug development and personalized medicine, limitations include insufficient validation and high costs.
Gene therapy is an experimental treatment that involves introducing genetic material into a person’s cells to fight or prevent disease. Researchers are studying gene therapy for a number of diseases, such as severe combined immuno-deficiencies, hemophilia, Parkinson's disease, cancer and even HIV, through a number of different approaches (see video: 'Gene Therapy a new tool to cure human diseases'). A gene can be delivered to a cell using a carrier known as a “vector.” The most common types of vectors used in gene therapy are viruses. The viruses used in gene therapy are altered to make them safe, although some risks still exist with gene therapy. The technology is still in its infancy, but it has been used with some success.
In this slide, You will get to learn abut Gene Therapy and different types of gene therapy. Various method of Gene Therapy and Advantage & Disadvantage and Recent advances in Gene Therapy.
This document discusses in silico drug design. It begins by defining drugs and the drug design process. Drug molecules should be small, complementary in shape to the target, and oppositely charged. In silico drug design uses computer simulations to identify drug target molecules. There are ligand-based and structure-based approaches. Key steps are selecting a disease and target, target validation, selecting ligands, applying scoring functions, lead optimization, and preclinical/clinical development. The goal is to eliminate compounds that may cause side effects or drug interactions. In silico methods help integrate new technologies with traditional medicinal chemistry experience to discover safe and effective drug leads.
This document discusses pharmacogenomics and how genetic differences can influence individual responses to drugs. It provides examples of how single nucleotide polymorphisms and other genetic variations can affect drug targets, metabolizing enzymes, transporters, and ultimately impact pharmacokinetics, pharmacodynamics, efficacy, and toxicity. Specifically, it examines cases of polymorphisms in cytochrome P450 drug metabolizing enzymes like CYP2C9, CYP2C19, and CYP2D6 that can lead to differences in drug metabolism and clearance between fast, normal, and poor metabolizers. The goals of pharmacogenomics are to maximize drug efficacy, minimize toxicity, and aid precision medicine by predicting who will respond to certain drugs. Widespread application
The document discusses pharmacogenomics and how genetic variations can affect individual responses to drugs. It describes how pharmacogenomics examines genomic loci and biological pathways to determine drug variability. It also discusses pharmacogenetics which focuses on single gene variants. The document outlines some merits of pharmacogenomics like improving drug safety and personalized treatment. It then discusses various scenarios on how genetic polymorphisms can impact different drug metabolism pathways. Finally, it examines how specific genetic variations in drug metabolizing enzymes and transporters can influence drug pharmacokinetics and potential adverse effects.
Role of Target Identification and Target Validation in Drug Discovery ProcessPallavi Duggal
Target identification and Validation tells about the how target is neccesary for new drug discovery and its development to reach into market for rare diseases.
- Pharmacogenomics deals with how genetic variations influence individual responses to drugs in terms of efficacy and toxicity. It aims to identify individuals who are more or less likely to respond to drugs or require altered doses.
- Pharmacogenetics studies variations in targeted genes or related genes, while pharmacogenomics uses genetic information to guide individualized drug and dose choice.
- Genetic polymorphisms like SNPs can result in different amino acids, protein changes, or no effect. They influence drug metabolism and response.
- Pharmacogenomics offers advantages like personalized medicine but faces barriers like complexity, education needs, and drug company incentives. It is being applied in various stages of clinical trials from target identification to dosing.
This document discusses drug discovery and the process of identifying potential new drug targets. It outlines the need for drug discovery to develop treatments for diseases without existing therapies. The key steps in drug discovery include target identification using genomics and proteomics to study the genome and map protein-protein interactions, as well as target validation using techniques like RNA interference and transgenic animal models. Bioinformatics plays an important role in analyzing large datasets to aid in drug target discovery and validation.
Proteomics is the study of proteins, including their composition, structure, function and interactions. It can be used to identify protein-protein interactions and complexes. Expression proteomics analyzes protein quantification and how levels are controlled. Proteomics has applications in new drug discovery by identifying proteins involved in diseases and developing drugs that target or inactivate those proteins. Genomics studies genomes and all their genes, DNA, and proteomes. It has applications in medicine, microbiology, forensics, agriculture and more. Metabolomics studies small molecule metabolites within cells and biofluids and their interactions, with applications in pharmacology, toxicology and functional genomics. Nutrigenomics examines how food constituents affect gene expression and identifies
This document summarizes a seminar on pharmacogenomics presented by Mr. Madhan Mohan Elsani. Pharmacogenomics is the study of how genes influence individual responses to drugs. Understanding genetic variations between individuals can help explain differences in drug efficacy and risk of adverse reactions. Single nucleotide polymorphisms (SNPs) are variations in DNA sequences that can impact how the body processes and metabolizes drugs. Pharmacogenomic testing can help optimize drug selection and dosing for individual patients based on their genetic makeup. This could improve drug safety and reduce adverse reactions.
Introduction to Immunotherapeutics
Cell mediated & humoral immunity, Immunosuppressants, Immunostimulants
Presented by
G. Sai Swetha
Department of Pharmacology
Genomics, proteomics, and bioinformatics are important fields that help advance drug development. Genomics studies entire genomes and can identify disease-associated genes. Proteomics identifies the proteins expressed in a sample and how they differ between healthy and diseased tissues. Bioinformatics uses computers to store and analyze biochemical and biological data, especially related to genomics. These fields help discover new drug targets, validate existing targets, select drug candidates, study mechanisms of action and toxicity. Integrating omics data from genomics to proteomics provides a more comprehensive understanding of biological systems compared to individual fields alone.
1. Gene mapping is the process of establishing the locations of genes on chromosomes, while gene sequencing determines the order of nucleotides within genes.
2. There are two main types of genome mapping - genetic mapping, which provides evidence that a disease is linked to genes, and physical mapping, which constructs maps by characterizing and assembling DNA fragments.
3. Restriction mapping uses restriction enzymes to cut DNA at specific sites, allowing genes to be mapped based on the resulting fragment sizes.
Antisense oligonucleotide therapy is a pharmacological approach that uses synthetic genetic material to inhibit protein translation by binding to mRNA. It works by blocking ribosomes, activating RNase enzymes, or forming triplex structures. Advantages include rapid manufacturing and potential for enhanced targeting. Limitations include short half-lives and difficulty directing to specific cells. Over 50 antisense compounds are in clinical trials for various diseases. The future of antisense-based therapies looks promising as more companies develop applications.
siRNA and miRNA both regulate gene expression, but through different mechanisms. siRNA targets specific gene sequences, while a single miRNA can regulate many genes. siRNA is found in plants, fungi, and insects but not mammals, which have other antiviral responses. miRNA are small non-coding RNAs around 22 nucleotides long that bind to mRNA to repress translation or promote degradation. They play important roles in development, physiology, and disease when their expression is dysregulated.
The document is a presentation by Manju Jakhar, who is an M.Pharm student in Pharmacology in their 2nd semester. Manju Jakhar will be presenting on their area of study and current level of education. The presentation provides basic identifying information about the presenter.
1. siRNA and miRNA are types of non-coding RNAs that play important roles in post-transcriptional gene regulation. siRNA induces gene silencing through RNA interference, while miRNA binds to target mRNAs to inhibit translation.
2. Both siRNA and miRNA have shown promise in developing therapies for diseases like cancer, asthma, neurodegenerative disorders, and viral infections by silencing genes involved in disease pathways. Delivery methods continue to be improved to enhance their therapeutic potential.
3. The key differences between siRNA and miRNA are their biogenesis, targeting specificity, and mechanisms of gene regulation. siRNA is synthesized from long double-stranded RNA and can perfectly complement target mRNAs, while miRNA originates from
This document provides an overview of pharmacogenetics and discusses:
1. Pharmacogenetics is the study of how genetic factors influence individual responses to drugs. It considers both environmental and genetic factors that impact drug metabolism and effects.
2. Key concepts include how genetic polymorphisms affect drug metabolizing enzymes and transporters, leading to variability in drug efficacy and risk of adverse reactions between individuals.
3. The field has progressed from early discoveries of genetic disorders affecting drug response to now understanding the effects of common gene variants, with the goal of personalized medicine to optimize drug therapy for each patient.
Genetic variation in drug transportersDeepak Kumar
This document discusses various transporter proteins involved in drug transport. It describes two main superfamilies - ATP-binding cassette (ABC) transporters and Solute-carrier (SLC) transporters. ABC transporters such as P-glycoprotein, MRP1, and BCRP act as efflux pumps and influence the bioavailability and toxicity of various drugs like irinotecan. Genetic variants in these transporters affect individual responses to drugs. SLC transporters import substances and influence drug absorption and distribution. Variations in transporter expression across tissues and individuals impact drug pharmacokinetics and treatment outcomes.
Gene therapy was once considered imaginary but has since made progress, including the first approved gene therapy treatment in 1990 for a girl with ADA deficiency. Gene therapy involves inserting genes into a person's cells to treat or prevent disease by replacing missing or defective genes. It can be done through viral or non-viral vectors and ex vivo or in vivo approaches. Recent advances include using gene therapy to regenerate heart cells in mice, MRI-guided brain cancer gene therapy, and stem cell gene therapy showing promise for treating neurological diseases. However, gene therapy still faces challenges like short-lived effects, immune responses, and difficulties treating multi-gene disorders.
Pharmacogenomics- a step to personalized medicinesApusi Chowdhury
Pharmacogenomics aims to optimize drug therapy based on a patient's genotype to maximize efficacy and minimize adverse effects. It involves studying how genetic factors influence individual responses to drugs in terms of absorption, distribution, metabolism, and excretion. Genetic polymorphisms like SNPs that occur in over 1% of the population can impact a drug's effects. Pharmacogenomic testing identifies biomarkers related to drug metabolism and targets to determine effective treatments and dosages for patients. While it holds promise for improving drug development and personalized medicine, limitations include insufficient validation and high costs.
Gene therapy is an experimental treatment that involves introducing genetic material into a person’s cells to fight or prevent disease. Researchers are studying gene therapy for a number of diseases, such as severe combined immuno-deficiencies, hemophilia, Parkinson's disease, cancer and even HIV, through a number of different approaches (see video: 'Gene Therapy a new tool to cure human diseases'). A gene can be delivered to a cell using a carrier known as a “vector.” The most common types of vectors used in gene therapy are viruses. The viruses used in gene therapy are altered to make them safe, although some risks still exist with gene therapy. The technology is still in its infancy, but it has been used with some success.
In this slide, You will get to learn abut Gene Therapy and different types of gene therapy. Various method of Gene Therapy and Advantage & Disadvantage and Recent advances in Gene Therapy.
Gene therapy involves introducing normal genes into patients to compensate for mutated genes that cause disease. The first gene therapy trial treated a girl with severe combined immunodeficiency. While it initially strengthened her immune system, the effects only lasted a few months. Gene therapy shows promise for diseases caused by single gene defects like cystic fibrosis, but faces challenges like short-lived effects, immune responses, and safety issues. Continued research aims to address these challenges through techniques like RNA interference and improved gene delivery methods.
Gene therapy aims to treat genetic disorders by introducing functional genes into patients' cells to compensate for mutated genes. The first gene therapy treatment was in 1990 for severe combined immunodeficiency. Viral vectors like retroviruses are often used to deliver therapeutic genes, but they sometimes cause immune reactions. While promising for single-gene disorders, gene therapy faces challenges like short-lived effects, immune responses, expense, and ethical concerns over uses for enhancement. Recent developments include using nanoparticles to target the brain and RNA interference for conditions like Huntington's disease. However, FDA approval of gene therapy products for sale has been limited due to past safety issues.
Gene therapy is an experimental technique that uses genes to treat or prevent disease. There are two types of gene therapy - somatic gene therapy, which treats cells of the body but not reproductive cells, and germline gene therapy, which treats reproductive cells and can be passed to future generations. There are several techniques for gene therapy including gene augmentation therapy, which adds a functional gene to replace a non-functioning one; gene inhibition therapy, which inhibits or interferes with a disease-causing gene; and gene killing therapy, which inserts a "suicide gene" to kill specific diseased cells. A key challenge is safely delivering the new gene to the right cells and ensuring it is expressed without disrupting other genes or triggering
This document provides an overview of gene therapy including its principles, approaches, development, types, vectors, delivery methods, examples, advantages, and disadvantages. Gene therapy involves inserting genes into cells to treat diseases caused by defective genes. There are two main approaches - germline gene therapy, which alters the germ cells and is passed to offspring, and somatic gene therapy, which alters non-reproductive cells only in the individual. Gene therapy development involves pre-clinical and clinical trials. Vectors like viruses are used to deliver therapeutic genes. Examples include treating severe combined immunodeficiency. While gene therapy has potential benefits, there are also risks like immune responses and ensuring genes reach the right cells.
Gene therapy holds promise for treating diseases like cancer, HIV, and genetic disorders. It works by inserting a normal gene to replace an abnormal one causing disease. Viruses are often used as vectors to deliver the new gene into cells. There are two main types: germline alters genes in reproductive cells and is unethical, while somatic only alters genes in other body cells. Gene therapy has had some success but also deaths, and faces ethical issues regarding cost, safety, and enhancement versus treatment of disease. It remains experimental but could help many if developed responsibly.
Gene therapy involves inserting genes into an individual's cells and tissues to treat disease. It can replace mutated genes, inactivate genes, introduce new genes, or cause cancer cells to kill themselves. Viral and non-viral vectors are used to deliver genes. Gene therapy has been applied to treat genetic disorders, cancer, heart disease, and more. Recent advances include using gene therapy to regenerate heart muscle cells, treat Sanfilippo syndrome and brain cancers, and combining cellular and gene therapies for breast cancer. RNA and DNA can be estimated using reactions that form colored complexes measured spectrophotometrically.
Gene therapy involves inserting a normal gene into cells to replace a mutated gene that causes disease. There are two main types - germline gene therapy affects reproductive cells and would alter the genes passed to future generations, while somatic gene therapy only affects the patient's body cells. Vectors like viruses are used to deliver the normal gene, but there are risks like unwanted immune reactions, infecting the wrong cells, or the vector virus recovering its ability to cause disease. While gene therapy holds promise, there remain technical limitations that must still be addressed.
This document discusses gene therapy, including its introduction, types, strategies, approaches, methods, target cells, and vectors. Gene therapy involves introducing genes into cells to treat genetic defects or diseases. There are two main types - somatic gene therapy targets somatic cells to treat an individual without inheritance, while germline gene therapy targets germ cells to make the therapy heritable. Common strategies include gene augmentation, targeted killing of diseased cells, inhibition of gene expression, and correction of mutated genes. Methods include ex vivo therapy of cultured cells outside the body and in vivo therapy of direct gene transfer inside the body. Viral and non-viral vectors are used to deliver therapeutic genes to different target cells depending on the disease.
This document discusses gene therapy, including its strategies, methods of delivery, history, and applications. It provides an overview of key concepts such as:
1. Gene therapy aims to treat genetic diseases by inserting normal genes into cells to compensate for abnormal genes. Strategies include gene replacement, gene augmentation, and gene inhibition.
2. Viruses are commonly used as vectors to deliver therapeutic genes. Retroviruses and adenoviruses integrate into the genome but can cause mutations, while adenoviruses are safer but less efficient.
3. The basic process involves isolating the normal gene, inserting it into a viral vector, infecting target cells, and having the cells produce functional proteins to return to
This presentation focuses on the science of Gene Therapy, the techniques of germ-line and somatic gene therapy and the mechanism of curing diseases and disorders using gene therapy. The presentation starts by discussing some common basic terms from genetics and moves on to the historical development of gene therapy techniques in chronological order. The different types of gene therapy techniques and their mechanisms have been discussed in detail subsequently. In concluding slides, some commercially available gene therapy products are mentioned and challenges of gene-therapy techniques have been highlighted.
Principal of genetic engineering & its applications laraib jameel
Genetic engineering has many applications in medicine, including producing insulin, human growth hormones, vaccines, and monoclonal antibodies to treat diseases. It is also used to create animal models of human diseases and potentially cure conditions through gene therapy or stem cell therapy. For example, genetically modified bacteria are used to mass produce human insulin for diabetes treatment. Researchers are also working on genetically engineering foods to contain vaccines to more easily deliver them in developing countries.
terapi gen kelainan genetik genetic disorders treatmentHendrik Sutopo
This document discusses various therapies for genetic disorders, including preventive methods, metabolic manipulation, gene product replacement, cell or organ transplantation, and somatic gene therapy. It provides details on preventive therapy through prenatal diagnosis and screening. Metabolic therapies include dietary restriction or supplementation, chelation, and metabolic inhibitors. Gene product replacement involves administering hormones, proteins, or enzymes. Somatic gene therapy introduces recombinant genes into somatic cells to treat genetic diseases. The document outlines the process of gene therapy and some challenges, such as immune responses, safety issues, and difficulties with multigenic disorders.
Gene therapy is the process of inserting genes into cells to prevent, treat or cure wide range of diseases. Gene therapy primarily involves genetic manipulations in animals or humans to correct a disease. Gene augmentation therapy: a DNA is inserted into the Genome to replace the missing gene product.Gene inhibition therapy: the antisense gene inhibits the expression of the dominant gene.
The document discusses several topics relating to molecular biology in medicine, including genetic disorders like phenylketonuria being identified through newborn screening, the use of techniques like electrophoresis and prenatal testing to diagnose genetic conditions, and rational drug design to develop treatments like anti-influenza drugs that target specific virus proteins. Gene therapy and recombinant DNA technology are also examined as approaches for treating inherited diseases.
This document discusses gene therapy, which involves introducing a normal functional gene into a patient's cells to correct a genetic disorder. It provides examples of genetic disorders that may be candidates for gene therapy, such as Down syndrome, cystic fibrosis, and sickle cell anemia. The document outlines the mechanisms of gene therapy, including using viral vectors to deliver therapeutic genes to targeted cells. Requirements for effective gene therapy and different methods like ex vivo and in vivo approaches are also summarized. Potential advantages include providing treatment for previously untreatable genetic diseases, while disadvantages include high costs and safety concerns.
Cancer arises due to genetic aberrations that accumulate in somatic cells and alter gene expression. There are several types of genomic changes including mutations, chromosome defects, and changes to oncogenes and tumor suppressor genes. Genetic testing can identify inherited cancer risk genes and guide diagnosis and treatment, while gene therapy holds promise for directly treating cancer at the genetic level.
This document discusses gene therapy, which involves introducing genes into cells to treat diseases. It describes two main approaches - somatic cell gene therapy, which targets non-reproductive cells, and germ line cell gene therapy, which is not currently attempted due to safety and ethical concerns. Two methods of gene delivery are described: ex vivo therapy involves culturing cells outside the body before reintroduction, while in vivo therapy directly delivers genes to target cells. Examples of successful gene therapies mentioned are for severe combined immunodeficiency, hemophilia, and blindness. Although promising, gene therapy faces challenges and high costs that limit widespread application currently.
Similar to Advances in Gene Therapy: Eyal Grunebaum (The Hospital for Sick Children) (20)
This document discusses strategies to improve access to drugs for rare diseases in Canada. It proposes establishing Centres of Expertise across the country to provide coordinated rare disease services. It also recommends creating a national rare disease research network and an accelerated drug access pathway. This would involve concurrent regulatory review and managed access programs to provide early access to drugs while collecting additional evidence. The goal is to deliver on the promise of value-based access to rare disease treatments for Canadians.
The document summarizes a webinar on rare diseases held on June 9th, 2023. It discusses the mandate of CORD-RQMO, which is a network of over 100 patient groups that aims to improve the lives of those with rare diseases. It outlines some of the services provided through IRARE, including information sharing and awareness raising. It also discusses challenges with drug access for rare diseases in Canada, including slow reimbursement processes and limited access and treatment for eligible patients. Finally, it announces that the federal government will invest up to $1.5 billion over 3 years in a new Rare Disease Drug Strategy to improve access to drugs and support for patients.
On this webinar, we’ll hear from experts on the issue and invite an open conversation with stakeholders. We need discussion, shared questions and answers and a review of case studies, which is why we are hosting this session.
Panelist:
Neil Palmer, Principal Consultant, WN Palmer & Co. and former PMPRB staff
Michael Dietrich, Executive Director, Policy, Innovative Medicines Canada
Laurene Redding, Global Head, Strategic Pricing (ex-China), BeiGene
Durhane Wong-Rieger, President & CEO, CORD
Moderator: Bill Dempster, CEO, 3Sixty Public Affairs
Rare Disease Drug Access within Rare Disease System
This document discusses challenges with rare disease drug access and proposes frameworks to address barriers. It summarizes an operational description of rare diseases developed by experts that includes a core definition and descriptive framework. The frameworks recognize challenges from a disease's rarity, the need for greater recognition of rare disease burden, and that addressing unmet needs requires coordinated action. The document also outlines health system pathways to treatment access and frameworks for mapping the drug journey and identifying barriers. It proposes three pillars - financing, health services, and governance - for optimal rare disease drug programs.
1) The document outlines Canada's strategy for rare diseases and rare drug access. It discusses the need for improved coordination between patients, healthcare providers, regulators, insurers, and industry.
2) A key focus is on patient engagement and empowerment throughout the process, from diagnosis to treatment to ongoing care. The roles and advocacy of patient groups have changed over time.
3) The strategy proposes several pillars to guide improvement, including increasing access to rare disease treatments consistently across Canada, optimizing evidence collection to inform decisions, supporting optimal patient outcomes and healthcare sustainability, and strengthening alignment between research and innovation systems and access objectives.
This document summarizes a presentation about creating Canada's rare disease network. It discusses barriers to accessing treatments, the role of physician advocacy, and an approach taken in Manitoba and Saskatchewan to build capacity for diagnosing hereditary metabolic disorders. A key part of this approach is the "OMICS First" strategy of starting with comprehensive DNA testing rather than traditional testing. This aims to improve timelines, reduce hospital stays and tests, and lower costs while maintaining quality of care. The presentation also discusses challenges of pricing for rare disease treatments and the need for real-world evidence to be incorporated into decision making.
CORD Rare Drug Conference: June 8-9, 2022
Registries and Real-World Data
INFORM RARE: Beth Potter, Alexandra Wyatt, Pranesh Chakraborty,
Monica Lamoureux, John Adams, Kim Angel
Orion Buske, CEO of Phenotypes, gave a presentation at the CORD Spring Conference in June 2022 about using patient phenotypes to drive genomic diagnostics for rare diseases. He explained that while genome sequencing can diagnose thousands of genetic conditions at once, clinicians need detailed phenotypic information to determine which are relevant to each patient's condition. PhenoTips is a digital platform that uses structured phenotypic data from sources like the Human Phenotype Ontology to help match patients to potential diagnoses, genes, and other related information to support precision medicine. It allows data sharing between hospitals, clinics, and research initiatives to help solve more rare disease cases.
This document summarizes a presentation by Dr. Kym Boycott on clinical genome-wide sequencing. The key points are:
- Genome-wide sequencing (GWS) can diagnose 25-60% of rare genetic diseases, improving patient care and reducing misdiagnoses. However, it requires specialized interpretation and many patients see multiple specialists over 3-6 years before receiving a diagnosis.
- Over 200,000 rare disease patients have been clinically sequenced worldwide. Guidelines developed in Canada recommend GWS for diagnostic evaluation.
- Projects in several Canadian provinces are working to implement clinical GWS, but a national data solution is needed to realize the promise of precision medicine for rare diseases in Canada.
- The proposed
CORD Rare Drug Conference: June 8-9, 2022
Registries and Real-World Data
INFORM RARE: Beth Potter, Alexandra Wyatt, Pranesh Chakraborty,
Monica Lamoureux, John Adams, Kim Angel Opportunities and Challenges for Data Management
CORD Rare Drug Conference June 8-9, 2022
Global, International, and National Rare Disease Networks
Rare Disease Research Network and National Children’s Hospital - Marshall
Summar, Rare Disease Institute
CORD Rare Drug Conference: June 8-9, 2022
Global, International, and National Rare Disease Networks
WHO-RDI Global Rare Disease Network - Matt Bolz-Johnson, EURORDIS
CORD Rare Drug Conference: June 8-9, 2022
Global, International, and National Rare Disease Networks
Canadian Network of Rare Disease Centres of Excellence - Paula Robeson, Children’s Healthcare Canada
Bonescanada.org aims to empower healthcare professionals and patients dealing with childhood-onset rare bone disorders through collaboration, a multidisciplinary team of experts, and overcoming challenges like limited resources, integrating research and care, and facilitating technology and regulatory processes. They have enrolled over 400 children in their research program on conditions like Duchenne muscular dystrophy and osteogenesis imperfecta, using centralized imaging to support international clinical trials. Lessons from research also inform their clinical program and advocacy efforts.
More from Canadian Organization for Rare Disorders (20)
Healthy Eating Habits:
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Tips for Healthy Eating: Offers practical advice such as incorporating a variety of foods, practicing moderation, staying hydrated, and eating mindfully.
Benefits of Regular Exercise:
Physical Benefits: Discusses how exercise aids in weight management, muscle and bone health, cardiovascular health, and flexibility.
Mental Benefits: Explains the psychological advantages, including stress reduction, improved mood, and better sleep.
Tips for Staying Active:
Encourages consistency, variety in exercises, setting realistic goals, and finding enjoyable activities to maintain motivation.
Maintaining a Balanced Lifestyle:
Integrating Nutrition and Exercise: Suggests meal planning and incorporating physical activity into daily routines.
Monitoring Progress: Recommends tracking food intake and exercise, regular health check-ups, and provides tips for achieving balance, such as getting sufficient sleep, managing stress, and staying socially active.
R3 Stem Cell Therapy: A New Hope for Women with Ovarian FailureR3 Stem Cell
Discover the groundbreaking advancements in stem cell therapy by R3 Stem Cell, offering new hope for women with ovarian failure. This innovative treatment aims to restore ovarian function, improve fertility, and enhance overall well-being, revolutionizing reproductive health for women worldwide.
The facial nerve, also known as cranial nerve VII, is one of the 12 cranial nerves originating from the brain. It's a mixed nerve, meaning it contains both sensory and motor fibres, and it plays a crucial role in controlling various facial muscles, as well as conveying sensory information from the taste buds on the anterior two-thirds of the tongue.
The best massage spa Ajman is Chandrima Spa Ajman, which was founded in 2023 and is exclusively for men 24 hours a day. As of right now, our parent firm has been providing massage services to over 50,000+ clients in Ajman for the past 10 years. It has about 8+ branches. This demonstrates that Chandrima Spa Ajman is among the most reasonably priced spas in Ajman and the ideal place to unwind and rejuvenate. We provide a wide range of Spa massage treatments, including Indian, Pakistani, Kerala, Malayali, and body-to-body massages. Numerous massage techniques are available, including deep tissue, Swedish, Thai, Russian, and hot stone massages. Our massage therapists produce genuinely unique treatments that generate a revitalized sense of inner serenely by fusing modern techniques, the cleanest natural substances, and traditional holistic therapists.
About this webinar: This talk will introduce what cancer rehabilitation is, where it fits into the cancer trajectory, and who can benefit from it. In addition, the current landscape of cancer rehabilitation in Canada will be discussed and the need for advocacy to increase access to this essential component of cancer care.
Comprehensive Rainy Season Advisory: Safety and Preparedness Tips.pdfDr Rachana Gujar
The "Comprehensive Rainy Season Advisory: Safety and Preparedness Tips" offers essential guidance for navigating rainy weather conditions. It covers strategies for staying safe during storms, flood prevention measures, and advice on preparing for inclement weather. This advisory aims to ensure individuals are equipped with the knowledge and resources to handle the challenges of the rainy season effectively, emphasizing safety, preparedness, and resilience.
DECODING THE RISKS - ALCOHOL, TOBACCO & DRUGS.pdfDr Rachana Gujar
Introduction: Substance use education is crucial due to its prevalence and societal impact.
Alcohol Use: Immediate and long-term risks include impaired judgment, health issues, and social consequences.
Tobacco Use: Immediate effects include increased heart rate, while long-term risks encompass cancer and heart disease.
Drug Use: Risks vary depending on the drug type, including health and psychological implications.
Prevention Strategies: Education, healthy coping mechanisms, community support, and policies are vital in preventing substance use.
Harm Reduction Strategies: Safe use practices, medication-assisted treatment, and naloxone availability aim to reduce harm.
Seeking Help for Addiction: Recognizing signs, available treatments, support systems, and resources are essential for recovery.
Personal Stories: Real stories of recovery emphasize hope and resilience.
Interactive Q&A: Engage the audience and encourage discussion.
Conclusion: Recap key points and emphasize the importance of awareness, prevention, and seeking help.
Resources: Provide contact information and links for further support.
Unlocking the Secrets to Safe Patient Handling.pdfLift Ability
Furthermore, the time constraints and workload in healthcare settings can make it challenging for caregivers to prioritise safe patient handling Australia practices, leading to shortcuts and increased risks.
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GEMMA Wean has an optimised nutritional balance and physical quality so that it flows more freely and spreads readily on the water surface. The balance of phospholipid classes to- gether with the production technology based on a low temperature extrusion process improve the physical aspect of the pellets while still retaining the high phospholipid content.
GEMMA Wean is available in 0.1mm, 0.2mm and 0.3mm. There is also a 0.5mm micro-pellet, GEMMA Wean Diamond, which covers the early nursery stage from post-weaning to pre-growing.
This particular slides consist of- what is Pneumothorax,what are it's causes and it's effect on body, risk factors, symptoms,complications, diagnosis and role of physiotherapy in it.
This slide is very helpful for physiotherapy students and also for other medical and healthcare students.
Here is a summary of Pneumothorax:
Pneumothorax, also known as a collapsed lung, is a condition that occurs when air leaks into the space between the lung and chest wall. This air buildup puts pressure on the lung, preventing it from expanding fully when you breathe. A pneumothorax can cause a complete or partial collapse of the lung.
Letter to MREC - application to conduct studyAzreen Aj
Application to conduct study on research title 'Awareness and knowledge of oral cancer and precancer among dental outpatient in Klinik Pergigian Merlimau, Melaka'
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Advances in Gene Therapy: Eyal Grunebaum (The Hospital for Sick Children)
1. Advances
in
gene
therapy
Eyal
Grunebaum
MD
Head,
Division
of
Immunology
and
Allergy
Senior
Scien<st,
Developmental
and
Stem
Cell
Biology
Hospital
for
Sick
Children,
Toronto
,
Ontario
Canadian
Expert
Pa<ents
in
Health
Technology
Conference
November
2016,
Toronto
1
2. Educational
objectives
• What
is
gene
therapy
(GT)
• Why
we
need
GT
(examples
from
immune
def.
pa<ents)
• How
we
do
GT
(outside
and
inside
the
body)
• When
do
we
now
use
GT
• What
innova<on
in
GT
are
expected
(CAR-‐T,
CRISPER).
• Goal:
Empower
you
to
be
able
to
advocate
effec<vely
for
GT,
when
appropriate.
No
financial
“conflicts
of
interest”.
2
3. Gene
therapy:
De:inition
GT
is
the
introduc<on
of
gene<c
material
into
cells,
which
will
then
be
translated
by
the
cell’s
machinery
to
a
protein,
to
compensate
for
exis<ng
abnormal
gene
or
to
make
a
beneficial
change
to
a
gene.
3
Genes
in
the
DNA
are
the
codes
for
making
proteins.
Proteins
determine
the
various
traits
in
our
body.
Gene
Protein
Trait
4. “Bubbles”
temporary
protect
kids
with
severe
immune
defects
• Children
born
without
an
immune
system,
2nd
to
gene<c
defects.
• Prone
to
life
threatening
infec<ons.
• Without
appropriate
interven<on,
condi<on
fatal
in
1st
few
years.
• Previously,
total
isola<on
to
prevent
infec<ons
(“bubble
babies”)
.
David
Veer
(1971-‐1983)
• Not
long
term
solu<on.
• Poor
quality
of
life,
significant
financial
&
mental
challenges.
4
Seinfeld,
1992,
“The
Bubble
Boy”
episode,
George
aacked
by
a
teenager
living
in
a
plas<c
bubble,
who
“losses
his
mind”.
5. Bone
marrow
transplantations
can
correct
severe
immune
defects
Transplan<ng
bone
marrow,
harvested
from
normal
donors,
to
restore
immunity
following
irradia<on,
chemo
or
immune
defects
(i.e.
“bubble
babies”).
Erythrocytes
Platelets
White
blood
cells
(immune
cells
to
fight
infec4ons)
Hematopoie<c
stem
cells
produce:
December
28th
1968
Bone
marrow
5
7. Graft
versus
host
response
has
major
impact
on
transplant
outcome.
Grunebaum
E,
Mazzolari
E,
Porta
F,
Dallera
D,
Atkinson
A,
Reid
B,
Notarangelo
LD,
Roifman
CM.
Bone
marrow
transplanta<on
for
severe
combined
immune
deficiency.
Journal
of
American
Medical
Associa<on.
2006.
In
North
America
d/t
small
families,
<20%
have
HLA
iden<cal
sibling
donor
Gene
therapy
with
pa<ents
own
“corrected”
cells
0
12
24
36
48
60
72
84
96
108
120
132
144
156
168
Months
after
bone
marrow
transplantation
100
50
10
60
70
80
90
Sibling
donors
with
identical
HLA
(92.3%)
Parents,
only
half
matched
HLA
(52.7%)
Survival
(%)
7
Example
from
pa<ents
with
severe
immune
defects
(12.5%
have
GvHD)
(61.4%
have
GvHD)
8. 1:
Gene
therapy
“outside
of
the
body”
How
is
it
done?
Cells
taken
from
pa<ent’s
BM
A
gene
of
interest
is
embedded
into
the
viruses’
DNA
“Altered”
viruses
are
mixed
with
the
pa<ent’s
cells
The
new
gene
integrates
into
the
cells’
DNA
and
is
expressed
as
a
protein
in
the
pa<ent’s
cells
Cells
injected
into
the
pa<ent
Altered
cells
expand
&
func<on
inside
the
body
8
In
the
lab,
viruses
(most
common
gene
delivery
tool)
altered
so
cannot
reproduce
or
cause
harm
9. Advantages
of
gene
therapy
vs
bone
marrow
transplants
include:
• Use
pa<ent’s
own
cells,
readily
available.
• No
“grae
versus
host”
response.
• No
risk
of
exposure
to
new
infec<ons
or
other
abnormali<es
donors
might
have
(and
not
know
about).
• Less
harm.
9
10. Gene
therapy
for
inherited
immune
defects.
• Pa<ents
with
adenosine
deaminase
deficiency,
type
of
inherited
severe
immune
deficiency,
were
the
1st
to
receive
gene
therapy
(1990),
followed
by
pa<ents
with
X-‐linked
severe
combined
ID.
• Done
only
aeer
extensive
work
in
labs
(cells,
animals,
etc).
• Used
only
for
pa<ents
with
no
other
treatment
op<ons.
Decade
of
disappointments:
• Difficul<es
in
introducing
the
new
genes
into
the
cells.
• Difficul<es
in
geqng
genes
to
func<on
&
produce
proteins.
• Difficul<es
ensuring
only
2
gene
copies
entered
(normally
there
are
only
2
gene
copies
in
a
cell).
• Difficul<es
in
controlling
the
expression
of
the
new
genes.
• Viruses
integrated
randomly
in
the
cells’
DNA,
ac<va<ng
“cancer
genes”,
leading
to
leukemia.
10
11. Improvements
over
time
in
gene
therapy
:
• Learned
that
“gene
corrected”
cells
need
“head-‐start”
to
overtake
pa<ent’s
exis<ng
cells
low
dose
chemotherapy
used
in
most
GT
protocols.
• Developed
beer
delivery
tools
with
improved
safety
and
efficacy.
• Beer
mechanisms
to
control
gene
expression,
using
endogenous
promoters
(“drivers”)
that
determine
expression.
• Enhanced
understanding
of
specific
disease
biology,
thereby
choosing
condi<ons
more
likely
to
benefit
from
GT.
• Earlier
iden<fica<on
of
pa<ents
through
newborn
screening,
enabling
therapy
of
kids
before
becoming
sick.
11
12. In
2006,
Parker
was
the
1st
Canadian
to
receive
“outside”
GT
(for
adenosine
deaminase
de:iciency)
through
the
“Milan”
GT
trial,
2016,
clinically
well,
normal
immunity.
Aug
2006
Aug
2016
12
13. Long-‐term
follow-‐up
of
gene
therapy
for
ADA
de:iciency
demonstrates
its
success
• All
18
ADA-‐deficient
pa<ents
who
received
GT
in
the
Milan
trial
are
alive.
None
developed
any
malignancy.
• 90%
of
them
have
normal
immune
func<on.
• (Cicalese
MP,
et
al.
Update
on
the
safety
and
efficacy
of
retroviral
gene
therapy
for
immunodeficiency
due
to
ADA
deficiency.
Blood.
2016)
• May
2016:
“The
European
Marke<ng
Authoriza<on
Commiee”,
the
FDA
equivalent,
approved
commercial
use
of
GT
for
adenosine
deaminase
deficiency.
[1st
out-‐of-‐body
GT
licensed
in
Western
countries!]
• Clinical
trials
of
GT
for
ADA
deficiency
are
currently
being
done
in
Los
Angeles
and
London.
13
14. Current
status
of
gene
therapy
for
immune
defects
(outside
of
the
body)
Clinical
trials
• Adenosine
deaminase
def.
• IL2Rg
deficiency
• Chronic
granulomatous
disease
• Wisko
Aldrich
syndrome
Pre-‐clinical
research
stages
• CD40
ligand
deficiency
• ZAP70
deficiency
• RAG1
deficiency
• RAG2
deficiency
• Artemis
deficiency
• Leukocyte
adhesion
defect
• Etc
Example:
We
have
been
working
on
GT
for
PNP
deficiency
for
a
decade,
and
have
at
least
5
years
<ll
clinical
trials.
(Liao
P,
Toro
A,
Min
W,
Lee
S,
Roifman
CM,
Grunebaum
E.
Len<virus
gene
therapy
for
purine
nucleoside
phosphorylase
deficiency.
J
Gene
Med.
2008)
14
15. Gene
therapy
for
immune
defects-‐
remaining
challenges.
1. Life-‐long
benefits
and
risks
are
not
known.
2. GT
needs
to
be
developed
separately
for
each
disease
(>300
genes
muta<ons
are
already
known
to
cause
immune
defects).
3. Each
of
these
condi<ons
requires
inves<ng
significant
resources
and
many
years
of
research.
4. Limited
access
in
USA,
not
(yet?)
in
Canada.
5. Pa<ents
and
families
need
to
travel
to
US/Europe.
6. Very
expensive
(US$250,000/pa<ent).
Support
by
MOH
appreciated,
however
non-‐sustainable,
par<cularly
if
we
plan
to
increase
the
#
of
pa<ents
receiving
GT.
15
16. “Out
side
of
the
body”
GT
for
many
other
non-‐immune
conditions
• Gene
therapy
where
bone
marrow
derived
cells
are
treated
with
virus
outside
of
the
body,
and
injected
back.
• Sickle
cell
anemia
• Fanconi
Anemia
• Thalassemia
• Metachroma<c
Leukodystrophy
• Adrenoleukodystrophy
For
addi<onal
condi<ons:
Clinical.Trails.gov
Storage
disorders
Hematological
diseases
16
17. • DNA
of
interest
delivered
directly
into
the
blood
or
<ssue/organ
using
viruses
(or
other
vehicles).
• Virus
inserts
itself,
and
the
DNA
of
interest,
into
the
cells
where
protein
is
expressed
by
the
cell’s
machinery.
17
2.
Gene
therapy
in
the
body
18. Gene
therapy
directly
in
the
body
• Advantages:
• No
need
to
remove
cells
from
the
pa<ent.
• When
disease
is
limited
to
specific
<ssue/organ,
the
gene
directly
delivered
to
<ssue/organ
(liver,
muscle,
brain,
tumor,
etc).
• More
delivery
methods
are
available
(viruses,
electricity,
lipids).
• These
“delivery
methods”
can
deliver
larger
genes.
• Easy
to
perform.
• Disadvantages:
• The
targeted
cells
usually
do
not
replicate
(nor
the
virus),
hence
effect
is
rela<vely
short,
oeen
necessita<ng
repeated
injec<ons.
• Repeated
injec<ons
might
cause
an
immune
response
against
the
virus,
thereby
jeopardizing
the
efficacy
of
gene
therapy.
• Might
“infect”
and
therefore
affect
neighboring
cells.
18
Because
of
rela<ve
ease,
became
very
popular
19. • Acute
Intermient
Porphyria
• Spinal
Muscular
Atrophy
1
• Duchenne
Muscular
Dystrophy
• Limb
girdle
muscular
dystrophy
• Amyotrophic
lateral
sclerosis-‐
(HGF)
• Painful
diabe<c
neuropathy-‐
(HGF)
• Leber's
Hereditary
Op<c
Neuropathy
• Choroideremia-‐
done
in
Edmonton
• Rare:
Neuronal
Ceroid
Lipofuscinosis
• Common:
Parkinson’s
disease
• Very
common:
Myocardial
infarct-‐
into
coronary
arteries
Direct
gene
delivery-‐
commonly
used
19
Into
the
blood
Into
the
muscles
Into
the
brain
Into
the
eye
20. • Skin
melanoma
(delivers
a
tumor
suppressor
molecule).
• Recurrent
Prostate
Cancer
(increases
chemo
uptake).
• Advanced
stage
head
and
neck
malignancies
• Breast
cancer
(delivers
IL12)
• Advanced
Pancrea<c
Cancer
• For
addi<onal
condi<ons:
Clinical.Trails.gov
Direct
gene
therapy
very
promising
in
treating
20
Cancer!
21. Chimeric
antigen
receptor
(CAR)-‐
T
cells
Treatment
of
B‑cell
malignancies
using
anF-‐CD19
CAR
T
cells.
Nat.
Rev.
Clin.
Oncol
2014
T
cell
ac<va<on
T
cell
expansion
Refractory
lymphoma
Viral
delivery
of
an<-‐CD19
CAR
“sensor”
CAR-‐T
infusion
chemo-‐
therapy
T
cell
Isola<on
21
“Arm”
pa<ents’
immune
cells,
outside
of
the
body,
with
an
engineered
“sensor”
that
searches
for
malignant
cells
22. Chimeric
antigen
receptor
(CAR)-‐
T
cells
• Clinical
trials
of
CAR-‐T
cells
to
leukemia,
lymphoma,
mul<ple
myeloma,
cervical
cancer,
and
many
more.
• Caveats:
• Some
pa<ents
do
not
have
enough
T
cells.
• Difficult
to
isolate
T
cells
and
insert
genes
into
them.
• T
cells
have
a
short
biological
half
life.
• Might
aack
“innocent
bystanders”
(similar
to
GvHD)
• Long-‐term
benefits
not
known
yet.
• Accessibility,
as
very
expensive
(>$350,000/treatment).
22
23. Next
generation
gene
therapy
(1)
• Cells
source:
usage
of
“induced
pleuri-‐potent
stem
cells”
such
as
pa<ent’s
skin
cells
that
are
“re-‐programed”
into
bone
marrow
cells
or
T
cells,
and
then
are
corrected
by
gene
therapy
outside
of
the
body.
• Safer
delivery
tools,
including
“destruc<on
switch”
that
can
be
turned
on
if
cells
are
causing
uncontrollable
damage,
or
an
“insulator”
to
prevent
effects
on
neighboring
genes.
• More
efficient
viruses.
24. Next
generation
gene
therapy
(2)
• CRISPER/Cas9
is
revolu<onary
targeted
gene
edi<ng
technology.
• Instead
of
“adding”
an
exogenous
gene,
correct
the
defect
in
the
exis<ng
gene
(outside
of
the
body).
• Advantage:
use
the
cell’s
own
regulatory
mechanisms.
• No
need
to
worry
about
the
number
of
copies
inserted.
• However,
each
defect
in
each
gene
needs
to
be
corrected
independently
(hundreds
of
muta<ons
in
each
of
the
hundreds
of
affected
genes.
Very
promising
technology!!
25. Conclusions:
Gene
therapy
has
moved
from
vision
to
clinical
reality
• Early,
GT
was
impeded
by
adverse
effects
and
low
efficacy.
• Understanding
mechanisms
led
to
sophis<cated
tools
with
improved
safety
and
efficacy.
• In
recent
years,
there
has
been
promising
progress,
sugges<ng
that
GT
is
an
appropriate
treatment
approach.
• Further
improvements
are
expected
in
the
near
future,
par<cularly
in
controlling
gene
expression
and
protein
func<on,
making
gene
therapy
even
more
arac<ve
therapeu<c
op<on.
• Remaining
biological
limita<ons
&
financial
accessibility
will
need
to
be
addressed
by
scien<sts
and
the
community,
respec<vely.
25
26. Acknowledgments
• Suppor<ve
medical
community
(Hospital
for
Sick
Children,
The
Blood
&
Marrow
Transplant
unit,
Dr.
Roifman
&
SK
colleagues).
• Na<onal
and
Interna<onal
colleagues
(Aiu<-‐
Milan,
Kohn-‐
L.A.)
• Funding
agencies
(SK
Founda<on,
D
&
A
Campbell,
CIHR,
etc).
• Ontario
Ministry
of
Health
(“Out
of
Country”
sec<on).
• !!
Trus<ng
pa<ents
and
families
!!
26
3
of
our
recent
children
who
received
gene
therapy