Abstract
Stem cell therapy offers a great advantage for the development of new treatments in the field of regenerative and restorative medicine. However, the use of stem cell therapies and their clinical indications can even be further improved using genetic modification of the cells. Due to the high level of consanguineous marriages in Turkey, the country suffers from an increased frequency of inborn genetically inherited diseases. Treatment of these diseases is difficult, since 1) diagnosis is often delayed in rural areas, 2) distance to specialized centers may be considerable, 3) treatment may require frequent hospital visits and 4) treatment procedures are often both invasive and expensive. Here, we discuss the current status of gene therapy of hematopoietic stem cells (HSCs) for rare, inherited monogenic diseases and the advantages to use these cells as an alternative treatment option for patients in Turkey. We discuss results of clinical trials using retroviral and lentiviral gene therapy for the treatment of immune deficiencies, hemoglobinopathies and several enzyme deficiencies, new developments in the field of the HSC gene therapy to improve safety and efficacy and recommendations for the future.
Highlights
Current treatment strategies for inherited monogenic diseasesThe rationale for stem cell gene therapy for inherited diseases is to provide the genome with a healthy copy of the gene as an addition to or as a replacement of the mutated gene in order to develop permanently curative treatment options for inherited monogenic diseases
Gene therapy in mitotic cells, such as hematopoietic stem cell (HSC), lymphoid progenitor cells and mature lymphocytes requires the use of a vector system such as retrovirus or lentivirus which are able to integrate in the host genome
In contrast to the gene therapy trials for X-severe combined immunodeficiency (SCID), no cases of leukemia related to insertional mutagenesis have been reported in patients treated for adenosine deaminase (ADA)-SCID (Aiuti et al 2007), despite the use of a similar γRV vector and the observation of a similar frequency of integration near LIM domain–only 2 (LMO2) and other protooncogenes (Aiuti et al 2007)
Summary
The rationale for stem cell gene therapy for inherited diseases is to provide the genome with a healthy copy of the gene as an addition to or as a replacement of the mutated gene in order to develop permanently curative treatment options for inherited monogenic diseases. Many hematopoietic diseases and enzyme deficiencies can be currently treated with hematopoietic stem cell (HSC) transplantation (Biffi 2017, Majhail et al 2015, Ringden et al 2018, Wynn 2011).
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