Updates on current advances in gene therapy / Actualizaciones acerca de los adelantos presentes en terapia genética

Gene therapy is the attempt to treat diseases by means of genetic manipulation. Numerous challenges remain to be overcome before it becomes available as a safe and effective treatment option. Retroviruses and adenoviruses are among the most commonly used viral vectors in trials. The retrovirus introduces the gene it carries into the target cell genome while the adenovirus introduces the gene into the target cell nucleus without incorporating it into the target cell genome. Other viral vectors such as adenoassociated viruses, pseudotyped viruses and herpes simplex viruses, are also gaining popularity. Proposed nonviral methods for gene transfer include physical methods and the employment of chemical vectors (lipoplexes, polyplexes and inorganic nanoparticles). Recent studies have investigated potential applications of gene therapy in correcting genetic diseases, treating malignant disorders and for treatment of other diseases. Trials on gene therapy for SCID and Leber's congenital amaurosis have achieved considerable success, but the widely publicized adverse reaction in Xlinked SCID patient receiving gene therapy raised concerns for safety profile of gene therapy. For that, several methods of improving safety and efficacy of gene therapy have been proposed. At present, the three main gene therapy strategies for treatment of cancer are application to oncolytic viruses, suicidegene therapy and genebased immunotherapy. Gendicine, the first approved anticancer drugs based on the use of gene therapy principle, is based on the use of oncolytic viruses. More evidence for wider clinical applications of gene therapy are expected as more gene therapy studies progress from the preclinical phase to clinical trial.

La terapia genética es el intento de tratar enfermedades por medio de la manipulación genética. Quedan aún numerosos retos que superar antes de que esté tipo de tratamiento se encuentre disponible como una opción segura y eficaz. Los retrovirus y los adenovirus se hallan entre los vectores virales más comúnmente utilizados en ensayos: el retrovirus introduce el gen - del cual es portador - en el genoma de la célula de destino, mientras el adenovirus introduce el gen en el núcleo de la célula de destino sin incorporarlo al genoma de la célula de destino. Otros vectores virales tales como los virus adenoasociados, los virus pseudotipados, y los virus del herpe simple, también están ganando popularidad. Los métodos no virales propuestos para la transferencia de genes incluyen tanto métodos físicos como el empleo de vectores químicos (lipoplexes, polisomas y nanopartículas inorgánicas). Estudios recientes han investigado las aplicaciones potenciales de la terapia genética en la corrección de las enfermedades genéticas, el tratamiento de los trastornos malignos y para el tratamiento de otras enfermedades. Los ensayos de terapia genética para SCID y la amaurosis congénita de Leber han logrado un éxito considerable, pero la reacción adversa ampliamente divulgada en el caso de los pacientes con SCID ligada al cromosoma, que recibían terapia génica, causó preocupación en cuanto al perfil de seguridad de la terapia génica. Por esa razón, se han propuesto varios métodos para mejorar la seguridad y la eficacia de la terapia génica. En la actualidad, las tres estrategias principales de terapia de genes para el tratamiento del cáncer son la aplicación de virus oncolíticos, la terapia con gen suicida, y la inmunoterapia genética. La gendicina, el primer medicamento anticancerígeno aprobado, basado en el uso del principio de la terapia génica, se basa en el uso de virus oncolíticos. Se esperan más evidencias a favor de aplicaciones clínicas más amplias de la terapia génica, a medida que más estudios de terapia génica progresan de la fase preclínica a la fase de ensayo clínico.

Recent progressions in stem cell research: breakthroughs achieved and challenges faced.

Stem cell studies have been conducted to study characteristics of stem cells, to develop better techniques for patient-specific stem cell lines generation, and to explore the therapeutic potential of stem cells. Techniques that enable efficient generation of new stem cell lines would facilitate research and allow generation of patient-specific stem cell lines for transplantation therapy. Somatic-Cell Nuclear Transfer (SCNT), which involves injection of donor cell nucleus into enucleated ovum, is the standard technique for new embryonic stem (ES) cell lines generation; presently its efficiency is low. A newer technique, pluripotent stem cell induction, reprograms somatic cells into induced pluripotent stem (iPS) cells by introducing certain factors into somatic cells. While certain adult stem cell treatments have been investigated on human participants, most ES cell or iPS cell treatments were still experimented on animal models. Recently, therapeutic potential of stem cell for several disorders was demonstrated. Researchers demonstrated stem cell's potential for treating hematologic disorders by correcting sickle cell anemia in rat model with iPS cells. Its potential role in treating cardiovascular disorder was demonstrated as injection of damaged rat heart with human ES cells derived cardiomyocyte plus "prosurvival" cocktail improved heart function. It might also treat nervous system disorders; injected into brain, ES cells derived neurons replace some loss cells in stroke rats and iPS cells derived neurons improved Parkinsonian syndrome in rats. Progress was also seen in other aspects of regenerative medicine. To overcome controversies caused by embryo destruction for obtaining ES cells, single blastomer stem cell derivation, Cdx2-inactivation, and parthenogenesis were proposed. All ES cell, iPS cell, and adult stem cell research should be continued with support from all sides.

Association between dietary intake of vitamin A, C, and E as antioxidants and cognitive function in the elderly at a nursing home.

As oxidative stress is considered one of the major mechanisms underlying degenerative changes, antioxidants from dietary sources, such as vitamin A, C, and E, may have protective effects against oxidative stress and thus be able to prevent or delay cognitive impairment in the elderly. This cross sectional study was designed to determine the association between dietary intake of vitamin A, C, and E and the presence of cognitive impairment in the elderly, along with other factors. Subjects included 36 residents from a nursing home in Jakarta, Indonesia. The data obtained including daily nutrition intake values one week prior to sampling converted from semi- quantitative food frequency questionnaire (SFFQ) results, Mini Mental State Examination (MMSE) scores, and anthropometrical measurement results. This study showed that while sex, age, education, nutritional status, and macronutrients intake were not significantly associated with presence of cognitive impairment, significant positive correlation existed between education and MMSE score (p=0.036, r=0.351). Higher vitamin A and vitamin C intake were shown to be significantly associated with lower incidence of cognitive impairment (p=0.022 and p=0.045, respectively). Moreover, vitamin C was shown to have significant positive correlation with MMSE score (p=0.031, r=0.359). However, the association between vitamin E and the presence of impairment was not significant (p=0.129). Higher intake of vitamin A and C may delay or prevent cognitive impairment in the elderly. Higher intake of vitamin C may contribute to better cognitive functioning. The findings may be explained by the two antioxidant vitamins’ protective effects against neurode generative processes cause by oxidative stress.