You will be surprised to know that through gene therapy a number of agonising and debilitating diseases will be pushed into history! Gene therapy involves changing the genetic information in a cell. For the ease of understanding genes, let me explain all the terms with relation to one another in a human cell.
Cells contain a nucleus, which is the controlling center of the cell. Nucleus contains chromosomes. Chromosomes are made up of genes, which in turn are made up of Deoxyribonucleic acid (DNA). Changes in the composition of DNA are very important in determining the expression of a gene. We talk about variant SARS Coronavirus, otherwise called mutation, causing Kent, South African and Indian variants of Covid-19. During mutation, there will be a deletion or addition of a nucleic acid, in the case of SARS coronavirus, it is Ribonucleic acid (RNA).
Gene therapy is intended to modify or manipulate the expression of a gene or to alter the biological properties of living cells for therapeutic use. Gene therapy is a technique that modifies a person’s genes to treat or cure disease. Gene therapies can work in several ways;
1)It replaces a disease causing gene with a healthy copy of the gene.
2) It inactivates a disease causing gene that is not functioning properly.
3)It introduces a new or modified gene to treat a disease.
Gene therapy techniques are used to treat diseases including cancer, genetic diseases, and infectious diseases. Gene Therapy Products (GTP) are biological products regulated by Centre for Biologic Evaluation and Research (CBER) of Food and Drug Administration (FDA) of America. Gene therapy products are the following;
1)Plasmid DNA, a circular DNA molecule which can be genetically engineered to carry therapeutic genes into human cells.
2)Viral Vectors, have a natural ability to deliver genetic materials into cells (that is how SARS coronavirus multiply in human cell), and therefore some gene therapy products are derived from viruses. Once viruses have been modified to remove their ability to cause infectious disease, these can be used as vehicles to carry therapeutic genes into human cells.
3)Bacterial Vectors, can be modified to prevent them from causing infectious diseases and then used as vehicles to carry therapeutic genes to human tissues.
4)Human gene editing technology is a method by which editing disrupts harmful genes or repairs mutated genes.
5)Patient Derived Cellular Gene Therapy Products is a technique in which cells are removed from patients and modified through viral vectors and then returned to patients.
There are stringent government regulations on
initiating and developing gene therapy in most developed countries.
First gene approved therapy was performed on a four year old child in
September 1990 to treat a genetic defect that left her with a severe
immune deficiency. Since then it was done on body cells for diseases
like Cystic Fibrosis, Familial Hypercholesterolemia, cancer, and severe
combined immunodeficiency (SCID). Marketing a gene therapy product
requires submission and approval by a Biologics License Application
(BLA).
If you search on the internet, you
will find laboratories offering gene therapy at a cost. There are
monogenic disorders, like Cystic Fibrosis, Familial
Hypercholesterolemia, and severe combined immunodeficiency (SCID),
sickle cell anaemia, hemophilia, Duchenne Muscular Dystrophy, Parkinson’s
Disease, Huntington’s Disease, chronic granulomatous disease, Fanconi’s
Disease, Alpha-1 antitrypsin deficiency and Gaucher’s disease. In these
diseases, the defective gene is in a single locus, and the diseases are
100% inherited. Nowadays many of these diseases with single locus
defect, can be treated.
There are genetic
diseases in which multiple loci are involved. In this category, diseases like diabetes, heart disease, cancers, schizophrenia and
Alzheimer’s disease, and infections like human immunodeficiency virus
disease (HIV) are included. Some of them are associated with unhealthy
lifestyle. By genetic analysis (mapping of genes), it is easy to determine whether someone
is likely to get the inherited disease. While I was practising two years ago, the representatives of genetic analysis companies were approaching me for promoting their business. By mapping genes, we can find out who is likely to get a single locus or multi loci genetic disease. Research is being carried
out to edit multiple gene defects and then to cure or improve the disease
process.
I shall explain step by step
the process of treating haemophilia through gene therapy. Haemophilia is an
inherited condition, in which the patient is having a deficiency of
factor 8 required for clotting. Patients with haemophilia suffer from
bleeding disorder on a minor cut or tooth extraction. The treatment for
haemophilia is called Roctavian treatment. In Roctavian therapy,
recombinant technology of adeno virus vector is used. Roctavian is a
modified gene, which is introduced into adeno virus. This is then
administered intravenously to the haemophilia patient.
Virus
vector (vehicle) has the inherent capacity to transfer its genetic material into
the host cell, in this case platelets. Once inside the platelet, the
modified genetic material multiplies exponentially and instructs the
tissues to manufacture factor 8 clotting factor. The study shows, there
is more than a 90% decrease in annual bleeding rate and more than 90%
decrease in factor VIII use, 3 years after having received an
effective dose of gene therapy. The Food and Drug Agency of America (FDA) will
be shortly approving treating haemophilia with gene therapy.
Gene
therapy cannot be administered on the second time as it invokes
antigen-antibody reaction. Other side effects of gene therapy include
enlargement of liver and allergy. However, its benefits immensely
outweigh the side effects. It is refreshing to note that in coming
years, more and more diseases will be amenable to gene therapy. Let us
hope the devastating misery of diseases like Duchenne Muscular Dystrophy,
Alzheimer’s, Parkinson’s and schizophrenia will be diseases of the
bygone days.
Dr. C.J.GEORGE FRCS
.jpg)
.jpg)
Comment Form