Gene therapy in hemophilia.
Hemophilia is a rarely encountered bleeding disorder in which blood fails to clot normally. People having this bleeding disorder bleed for a quite long time as compared to others after getting injured. There are also internal bleedings in areas like knees, ankles, and elbows. The internal bleeding can result in organ damage and can also be fetal. The disorder is heritable through the genes. People having this disorder lack the clotting factor which is a protein required for the blood to clot normally. There are various types of clotting factors which function together with platelets to help the blood to clot (The New England Journal of Medicine, 2009).
Platelets are blood cells which are produced in the bone marrow and they are involved in blood clotting mechanism. When there is an injury to the blood vessels, the clotting factors enables the platelets to come together and block the cuts and breaks which have resulted from the injury. When the clotting factors are absent, the normal clotting mechanism cannot go on. There are injections of clotting factors which have been formulated to help hemophiliacs whenever they are injured.
There are two types of hemophilia which are type A and type B. In type A hemophilia, there is absence of even low levels of clotting factor VIII. About 90 of people suffering from this bleeding disorder are reported to be having type A. In hemophilia type B, there is lack of or low levels of clotting factor IX. Hemophilia can be rarely acquired during the lifetime. This can be possible when the body starts to manufacture antibodies against the clotting factors and these factors are found in the blood stream (Fakharzadeh, 2004).
Genes
Genes are the biological units of inheritance. They determine clear characters like hair and eye color, and also some complex traits like the ability of the blood to be able to carry oxygen. Much complicated characteristics like physical strengths may come as a result of interaction among various numbers of genes together with environmental influences (Science News, 2009).
Genes are found inside the chromosomes which are located in the nucleus of the cells. They are composed of DNA which is one of the types of biological molecules. Humans are estimated to have between 30,000 to 40, 000 genes. Genes have the commands that enable the cells to produce particular proteins such as enzymes. For the proteins to be manufactured, the cell must first of all copy the information which is found in the genes into another biological molecule called ribonucleic (RNA). The cells mechanism of protein synthesis then takes the information copied into the RNA to produce a particular protein. There are specific genes which are active at any particular time, while as the cells become aged, most of the genes become inactive permanently. Mistakes in the genes can lead to a disorder (Arruda, 2009).
Gene therapy
Developments in appreciating and manipulating genes have set a platform for the scientists to change an individuals genetic material in order to treat or prevent diseases. Gene therapy is an investigational therapy that entails introducing genetic material which can either be DNA or RNA into an individuals cell so as to battle the disease. This method is currently being studied in clinical experiments for several types of cancer and other ailments. It is only available under clinical trials (Murphy, High, 2008).
How the gene therapy works
The gene therapy is intended to bring in genetic materials into the cells to compensate for the defective genes or even to manufacture a useful protein. If its the mutated that causing a necessary protein to be defective or missing, gene therapy is capable of introducing a normal copy of genes to re-establish the function of the clotting protein (Giuseppe, Massimo, , Evgueni 2009). The gene is not introduced directly into the cell but it is done through a carrier known as vector, which is genetically made to introduce the genes. Some viruses have been employed as vectors since they can introduce the new gene to the cell by infecting it. The viruses are changed so that they cannot cause diseases when they are used for this purpose. Viruses like retroviruses are capable of integrating their genes and the new gene into the chromosome found in the human cell. Adenoviruses are capable of inserting their DNA into the nucleus of the other cell, but the DNA is not constituted into the chromosome (Arruda, 2009).
The carrier having the gene can be introduced into a definite tissue in the body through injection or injected intravenously where it is absorbed by cells. The other way of introducing the carrier vector would involve removal of the patients cells and exposing them to the vector in the laboratory. After the cells have been infected by the vector, they are put back into the body of the patient. If the therapy succeeds, the new gene introduced by the vector carrier will initiate the manufacture of the clotting factors (Chuah, Collen, Driessche, 1998). There are several technical challenges which must be resolved before making gene therapy a practical method of treating hemophilia. The main challenges include getting best way of introducing the genes and taking them to specific cells. The scientists must also make sure that the newly introduced genes are clearly regulated by the body (Henahan, 1998).
Current studies on gene therapy
Gene therapy is under investigation to approve its application in the treatment of cancer. Some of the methods aim at healthy cells to improve their ability to battle cancer. Other methods aim at cancer cells to wipe out them or to prevent them from growing. The following are some of the gene therapy techniques which are currently under study. In one method, the researchers substitute lacking or changed genes with ones which are normal. Since the lacking or altered genes can result into a disease, replacing them can be employed in the treatment of cancer (Giuseppe, Massimo, , Evgueni 2009).
There are also studies on how to enhance patients immune system so as to fight cancer. Gene therapy is employed in this approach to arouse the bodys natural response to fight cancerous cells. In one of the methods under this approach, the patients blood sample is taken and the new genes are inserted which causes the cells to manufacture proteins which are also known as T-cell receptors. The new genes inserted are then taken to the patients leukocytes then back. The leukocytes will then produce T-cell receptors which will embed on the outer coat of leukocytes. The T-cell receptors will notice and attach to some molecules which are located on the surface of cancerous cells. The T-cell receptors will in turn activate the leucocytes to attack and kill the cancerous cells (Chuah, Collen, Driessche, 1998).
There are also efforts being made on how to insert new genes into cancerous cell to make them prone to chemotherapy, radiation therapy, or other methods of cancer treatments. Still on the efforts of how to treat cancer, there is another study which involves removal of normal blood forming stem cells from the patients body, introduce a gene which enables these cells to resist side effects of high doses of anti cancer drugs and then the cells are introduced back into the patients body (Fakharzadeh, 2004).
Another research on gene therapy involves insertion of suicide genes into the cancer cells. An inactivated form of toxic cancer drug is then administered. The drug administered is then activated inside the cancer cells which have the suicide genes. All these events results in the killing of the cancer cells. Gene therapy is also involved in a research to avoid cancer cells from creating new blood vessels which supply them with nutrients and oxygen. If this is done, the cancer cells end up dying (Arruda, 2009).
Experiments have been conducted on the usefulness of gene therapy in treatment of hemophilia. The experiment was conducted on dogs that had genetic disorder which was increasing their chances of developing hemophilia type B. Working genes which are able to manufacture the clotting factor IX were then carried by adenovirus vector and injected into the patients. The theory behind this trial was that the virus which has the genes would deliver the gene which was missing in these animals muscle cells which would accept the genes and start manufacturing the clotting factor needed (factor IX) and release it into the bloodstream.
The trial resulted in some reduced clotting time in these animals. It took around 60 days for the blood clotting time to come back to normal and this status remained stable for about one year after the initial treatment. There were neither side effects of the experiment nor limiting immune response which were noticed due to the therapy. The gene introduction method employed in this experiment led to unrelenting expression of factor IX at level considered sufficient to reveal improvement in blood coagulation time as compared to before treatment. Gene transfer methods employed in large animals are giving good results as compared to those done in small animals like mice (Chuah, Collen, Driessche, 1998). The strategy on treatment of human hemophilia type B has advanced to the clinical trials. Food and Drug Administration is about to start the first phase clinical trials in 10 to 20 adults who have been diagnosed with hemophilia type B (Herzog, 2004).
The main concerns associated with gene therapy
The viruses which are used as vectors may end up infecting unintended cells. They may end up infecting both healthy and cancerous cells. The new gene may also end up in a wrong location in the DNA which might end up causing dangerous mutations to the biological molecule or the cancer cells. The new genes may also get delivered into the reproductive cells of the patient. This might result into adverse changes that might be inherited by the children if the patient is still giving birth (Arruda, 2009).
The other concerns include a situation where the new introduced gene is expressed excessively resulting into harmful levels. The delivering virus can also result into inflammation or immune response. There is also a possibility that the virus used can be transmitted from the patient to other people or to the surrounding. In order to avoid such risks, the trials are done using animals so as to asses the possibility of the occurrence of the raised concerns (Henahan, 1998).
Platelets are blood cells which are produced in the bone marrow and they are involved in blood clotting mechanism. When there is an injury to the blood vessels, the clotting factors enables the platelets to come together and block the cuts and breaks which have resulted from the injury. When the clotting factors are absent, the normal clotting mechanism cannot go on. There are injections of clotting factors which have been formulated to help hemophiliacs whenever they are injured.
There are two types of hemophilia which are type A and type B. In type A hemophilia, there is absence of even low levels of clotting factor VIII. About 90 of people suffering from this bleeding disorder are reported to be having type A. In hemophilia type B, there is lack of or low levels of clotting factor IX. Hemophilia can be rarely acquired during the lifetime. This can be possible when the body starts to manufacture antibodies against the clotting factors and these factors are found in the blood stream (Fakharzadeh, 2004).
Genes
Genes are the biological units of inheritance. They determine clear characters like hair and eye color, and also some complex traits like the ability of the blood to be able to carry oxygen. Much complicated characteristics like physical strengths may come as a result of interaction among various numbers of genes together with environmental influences (Science News, 2009).
Genes are found inside the chromosomes which are located in the nucleus of the cells. They are composed of DNA which is one of the types of biological molecules. Humans are estimated to have between 30,000 to 40, 000 genes. Genes have the commands that enable the cells to produce particular proteins such as enzymes. For the proteins to be manufactured, the cell must first of all copy the information which is found in the genes into another biological molecule called ribonucleic (RNA). The cells mechanism of protein synthesis then takes the information copied into the RNA to produce a particular protein. There are specific genes which are active at any particular time, while as the cells become aged, most of the genes become inactive permanently. Mistakes in the genes can lead to a disorder (Arruda, 2009).
Gene therapy
Developments in appreciating and manipulating genes have set a platform for the scientists to change an individuals genetic material in order to treat or prevent diseases. Gene therapy is an investigational therapy that entails introducing genetic material which can either be DNA or RNA into an individuals cell so as to battle the disease. This method is currently being studied in clinical experiments for several types of cancer and other ailments. It is only available under clinical trials (Murphy, High, 2008).
How the gene therapy works
The gene therapy is intended to bring in genetic materials into the cells to compensate for the defective genes or even to manufacture a useful protein. If its the mutated that causing a necessary protein to be defective or missing, gene therapy is capable of introducing a normal copy of genes to re-establish the function of the clotting protein (Giuseppe, Massimo, , Evgueni 2009). The gene is not introduced directly into the cell but it is done through a carrier known as vector, which is genetically made to introduce the genes. Some viruses have been employed as vectors since they can introduce the new gene to the cell by infecting it. The viruses are changed so that they cannot cause diseases when they are used for this purpose. Viruses like retroviruses are capable of integrating their genes and the new gene into the chromosome found in the human cell. Adenoviruses are capable of inserting their DNA into the nucleus of the other cell, but the DNA is not constituted into the chromosome (Arruda, 2009).
The carrier having the gene can be introduced into a definite tissue in the body through injection or injected intravenously where it is absorbed by cells. The other way of introducing the carrier vector would involve removal of the patients cells and exposing them to the vector in the laboratory. After the cells have been infected by the vector, they are put back into the body of the patient. If the therapy succeeds, the new gene introduced by the vector carrier will initiate the manufacture of the clotting factors (Chuah, Collen, Driessche, 1998). There are several technical challenges which must be resolved before making gene therapy a practical method of treating hemophilia. The main challenges include getting best way of introducing the genes and taking them to specific cells. The scientists must also make sure that the newly introduced genes are clearly regulated by the body (Henahan, 1998).
Current studies on gene therapy
Gene therapy is under investigation to approve its application in the treatment of cancer. Some of the methods aim at healthy cells to improve their ability to battle cancer. Other methods aim at cancer cells to wipe out them or to prevent them from growing. The following are some of the gene therapy techniques which are currently under study. In one method, the researchers substitute lacking or changed genes with ones which are normal. Since the lacking or altered genes can result into a disease, replacing them can be employed in the treatment of cancer (Giuseppe, Massimo, , Evgueni 2009).
There are also studies on how to enhance patients immune system so as to fight cancer. Gene therapy is employed in this approach to arouse the bodys natural response to fight cancerous cells. In one of the methods under this approach, the patients blood sample is taken and the new genes are inserted which causes the cells to manufacture proteins which are also known as T-cell receptors. The new genes inserted are then taken to the patients leukocytes then back. The leukocytes will then produce T-cell receptors which will embed on the outer coat of leukocytes. The T-cell receptors will notice and attach to some molecules which are located on the surface of cancerous cells. The T-cell receptors will in turn activate the leucocytes to attack and kill the cancerous cells (Chuah, Collen, Driessche, 1998).
There are also efforts being made on how to insert new genes into cancerous cell to make them prone to chemotherapy, radiation therapy, or other methods of cancer treatments. Still on the efforts of how to treat cancer, there is another study which involves removal of normal blood forming stem cells from the patients body, introduce a gene which enables these cells to resist side effects of high doses of anti cancer drugs and then the cells are introduced back into the patients body (Fakharzadeh, 2004).
Another research on gene therapy involves insertion of suicide genes into the cancer cells. An inactivated form of toxic cancer drug is then administered. The drug administered is then activated inside the cancer cells which have the suicide genes. All these events results in the killing of the cancer cells. Gene therapy is also involved in a research to avoid cancer cells from creating new blood vessels which supply them with nutrients and oxygen. If this is done, the cancer cells end up dying (Arruda, 2009).
Experiments have been conducted on the usefulness of gene therapy in treatment of hemophilia. The experiment was conducted on dogs that had genetic disorder which was increasing their chances of developing hemophilia type B. Working genes which are able to manufacture the clotting factor IX were then carried by adenovirus vector and injected into the patients. The theory behind this trial was that the virus which has the genes would deliver the gene which was missing in these animals muscle cells which would accept the genes and start manufacturing the clotting factor needed (factor IX) and release it into the bloodstream.
The trial resulted in some reduced clotting time in these animals. It took around 60 days for the blood clotting time to come back to normal and this status remained stable for about one year after the initial treatment. There were neither side effects of the experiment nor limiting immune response which were noticed due to the therapy. The gene introduction method employed in this experiment led to unrelenting expression of factor IX at level considered sufficient to reveal improvement in blood coagulation time as compared to before treatment. Gene transfer methods employed in large animals are giving good results as compared to those done in small animals like mice (Chuah, Collen, Driessche, 1998). The strategy on treatment of human hemophilia type B has advanced to the clinical trials. Food and Drug Administration is about to start the first phase clinical trials in 10 to 20 adults who have been diagnosed with hemophilia type B (Herzog, 2004).
The main concerns associated with gene therapy
The viruses which are used as vectors may end up infecting unintended cells. They may end up infecting both healthy and cancerous cells. The new gene may also end up in a wrong location in the DNA which might end up causing dangerous mutations to the biological molecule or the cancer cells. The new genes may also get delivered into the reproductive cells of the patient. This might result into adverse changes that might be inherited by the children if the patient is still giving birth (Arruda, 2009).
The other concerns include a situation where the new introduced gene is expressed excessively resulting into harmful levels. The delivering virus can also result into inflammation or immune response. There is also a possibility that the virus used can be transmitted from the patient to other people or to the surrounding. In order to avoid such risks, the trials are done using animals so as to asses the possibility of the occurrence of the raised concerns (Henahan, 1998).
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