 deaminase. The experiment was extremely labor intensive, because mature peripheral-blood T cells were modified rather than stem cells, and the procedure therefore had to be repeated many times to achieve success.
- 2. Parkinson’s Disease:
- Neurologix a biotech company announced that they have successfully completed its
- landmark Phase I trial of gene therapy for Parkinson’s Disease.
- This was a 12 patient study with four patients in each of three dose escalating
- cohorts. All procedures were performed under local anesthesia and all 12 patients
- were discharged from the hospital within 48 hours of the procedure, and followed
- for 12 months. Primary outcomes of the study design, safety and tolerability, were
- successfully met. There were no adverse events reported relating to the treatment
- The gene transfer procedure utilized the AAV (adeno-associated virus) vector, a virus
- that has been used safely in a variety of clinical gene therapy trials, and the vehicle that
- will be used in all of the company’s first generation products, including epilepsy and
- Huntington’s disease. In its Parkinson’s disease trial, Neurologix used its gene transfer
- Genes get into brain using liposomes coated in polymer called polyethylene glycol
potential for treating Parkinson’s disease
- RNA interference or gene silencing to treat Huntington’s
siRNAs was used to degrade RNA of particular sequence and so abnormal protein won’t be
- Create tiny liposomes that can carry therapeutic DNA through pores of nuclear
- Sickle cell successfully treated in mice
- Due to every method of gene transfer having shortcomings, there have been some hybrid methods developed that combine two or more techniques.
- Virosomes are one example; they combine liposomes with an inactivated HIV or influenza virus. This has been shown to have more efficient gene transfer in respiratory epithelial cells than either viral or liposomal methods alone. Other methods involve mixing other viral vectors with cationic lipids or hybridizing viruses.
Some of the problems of gene therapy include:
- Short-lived nature of gene therapy – Before gene therapy can become a permanent cure for any condition, the therapeutic DNA introduced into target cells must remain functional and the cells containing the therapeutic DNA must be long-lived and stable. Problems with integrating therapeutic DNA into the genome and the rapidly dividing nature of many cells prevent gene therapy from achieving any long-term benefits. Patients will have to undergo multiple rounds of gene therapy.
- Immune response – Anytime a foreign object is introduced into human tissues, the immune system has evolved to attack the invader. The risk of stimulating the immune system in a way that reduces gene therapy effectiveness is always a possibility. Furthermore, the immune system‘s enhanced response to invaders that it has seen before makes it difficult for gene therapy to be repeated in patients.
- Problems with viral vectors – Viruses, the carrier of choice in most gene therapy studies, present a variety of potential problems to the patient —toxicity, immune and inflammatory responses, and gene control and targeting issues. In addition, there is always the fear that the viral vector, once inside the patient, may recover its ability to cause disease.
- Multigene disorders – Conditions or disorders that arise from mutations in a single gene are the best candidates for gene therapy. Unfortunately, some of the most commonly occurring disorders, such as heart disease, high blood pressure, Alzheimer’s disease, arthritis, and diabetes, are caused by the combined effects of variations in many genes. Multigene or multifactorial disorders such as these would be especially difficult to treat effectively using gene therapy.
- Chance of inducing a tumor (insertional mutagenesis) – If the DNA is integrated in the wrong place in the genome, for example in a tumor suppressor gene, it could induce a tumor. This has occurred in clinical trials for X-linked severe combined immunodeficiency (X-SCID) patients, in which hematopoie