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Statistics |
| Unique Visitors: 33 |
| Total Unique Visitors: 58197 |
| Visitors Out: 796 |
| Total Visitors Out: 1254 |
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| Conclusion |
| 2010-12-01 06:15:00 |
Gene therapies are currently being studied in more than 50 clinical trials. This method holds considerable promise for many inborn errors of metabolism. Gene therapy for inborn errors of metabolism requires the development of biologically sound strategies for correcting metabolic defects, vectors for controlling the expression of therapeutic genes, and methods for delivering vectors safely to patients. The clinical applicability of gene therapy will require increased attention not only to the potential effectiveness of gene delivery as a therapeutic modality, but to clinical issuesincluding safety, pharmacology, toxicology, compliance, and economics. Extensive clinical investigation will be required to assess the role of gene therapy relative to conventional and evolving pharmaceutical, bi...
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| Towards Clinical Applications |
| 2010-12-01 06:13:00 |
The efficacy of gene therapy will ultimately need to be assessed and demonstrated relative to conventional therapeutics. While it is widely believed that many inborn errors of metabolism may come to be best treated by gene therapy, these will also be significant advances in the development of conventional pharmaceutical products, biological products such as enzyme replacement, and transplantation, including the potential for inducing tolerance to allogeneic or xenogeneic grafts. The question “Why gene therapy?”must be answered by showing that proposed gene therapies are more effective and safer than other therapies, provide adequate compliance, and are cost-effective relative to other therapies. The present focus of gene therapy is on demonstrating that gene replacement is feasible and...
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| Clinical Indications |
| 2010-12-01 06:08:00 |
The first clinical trials using retroviral vectors demonstrated the feasibility and social and regulatory acceptance of gene transfer into human subject. The initial trials have greatly expanded interest in gene therapy and led to a more focused analysis of the potential clinical indications for gene therapy. To date, the number of patients treated is still too small to fully assess the safety or efficacy of either retroviral vectors or any specific gene therapy.Gene replacement is now commonly performed in research laboratories studying inborn errors of metabolism, and more than 100 diseases have been “curred” in experiments performed in cells cultured from affected patients. The list of potential diseases for gene therapy now encompasses virtually any inborn error of metabolism for ...
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| Current Clinical Trials |
| 2010-12-01 06:06:00 |
Since the commencement of the first clinical trial involving gene transfer into human subjects in 1989, more than 100 patients have been treated and more than 100 patients have been treated and more than 70 clinical trials are underway. Many of the ongoing clinical trials are gene marking trials, in which genes are introduced into cells prior to transplantation to study their fate and function. The majority of current clinical trials are aimed at gene therapy for cancer. Other are aimed at exploring the potential of gene therapy for inborn errors of metabolism including adenosine deaminase deficiency,familial hypercholesterolemia, Gaucher’s disease, and cystic fibrosis.The first therapeutic trials involved the introduction of a gene for adenosine deaminase into the cultured lymphocytes f...
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| DNA Vector Delivery |
| 2010-12-01 05:55:00 |
It is also possible to delivery DNA vectors directly to cells withouth the use of viruses. This involves the application of pharmaceutical methods for drug delivery to target DNA vectors to specific cells after direct administration to patients and to enhance the process by which DNA vectors are taken into cells and traffick to the nucleous were transcription can take place. In particular, pharmaceutical experience with liposomes and other particulate drug carriers may be employed indrug delivery. Various different approaches have been described for DNA delivery,including the use of purified DNA administered directly into the body by intramuscular injection, the use of ballistic particles coated with DNA, the use of cationic livids, and the use of various ligans to target DNA to specif...
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| Cell Based Therapy |
| 2010-12-01 05:52:00 |
Organ transplantation in itself o form of gene therapy in which alloogenic cells containing a normal gene are implanted into the body. Genetic manipulation may be used to enchance transplantation therapy, both, by allowing genetic correction of autologous cells which canthen be transplanted into patients, or by allowing modification of allogenic or xenogeneic cells to make them less antigenic. These methods continue to be limited by the lack of established clinical methods for cellular transplantation....
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| Viral Vector Delivery |
| 2010-12-01 05:49:00 |
The initial strategies for gene therapy involved the construction of viral vectors in which the expression vector was packaged into a virus particle that was capable of invecting cells. The premise of developing viral vectors was that it might be possible to exploit, for therapeutic purpose, the highly evolved ability of viruses to introduce their genes into certain cells. To do this, strategies were developed for constructing attenuated or defective viral vectors that were capable of carrying therapeutic genes into cells butwere incapable of further propagation in patients, and were incapable of inducing viral pathogenesis. Many different viruses have been proposed as vihicles for vector delivery, and most of the clinical trials performed to date employ viral vectors.The viruses which hav...
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| Vectors |
| 2010-12-01 05:44:00 |
The function of a vector is to control how much of the therapeutic product is produced and where in the body it is produced. Effective gene therapy requires that a therapeutic gene be introduced into cells of the body in a form which allows the gene (DNA) to be transcribed into mRNA, for the mRNA to be properly processed within the cell, for the mRNA to be translated into a protein, and for this protein to be properly modified, to reach the appropriate compartment, and to properly function. This a achieved by constructing an expression vector which contains the genetic sequences encoding the therapeutic protein combined with genetic elements that control the processes of transcription, RNA splicing, translation, andpost-translational modification of the protein. Often it is desirable to h...
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| Therapeutic Genes |
| 2010-12-01 05:39:00 |
In its simplest form, gene therapy for inherited metabolic disease involves introducing a gene into a patient to express an enzyme which the patient lacks because of an inherited genetic defect. Examples of such therapy would be the replacement of phenylalanine hydroxylase in patients with phenylketonuria or the low-density lipoprotein (LDL) receptor in patients with familial hypercholesterolemia. This approach to gene therapy would be applicable to most autosomal recessive diseases and many X-linked diseases where one copy of the normal gene orin many cases even a fraction of normal enzymatic activity is known to prevent the pathological phenotype of the disorder. Autosomal dominant disorders would be more difficult targets for gene therapy, since simple replacement of a defective gene ...
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| Somatic Gene Therapy |
| 2010-12-01 05:32:00 |
Inborn errors of metabolism, like most disease, have both genetic and environmental components. Current therapy for inborn errors of metabolism focuses on the diagnosis of a genetic defect before the onset of clinical symptoms, which allows changes to be made in the environment of the patient to prevent the progression of the pathological disease process. Dietary therapy and drug therapy are not directed at altering the genetic component of the inborn error of metabolism, but rather its environmental component. The prototype for this approach to treating inborn errors of metabolism is dietary therapy for phenilketonuria, in which the body’s genetic inability to metabolize phenylalanine is treated by eliminating this amino acid from the environment. Such therapies are effective for som...
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