Decreased quality of life in Duchenne muscular disease patients related to functional neurological and cardiac impairment.

In this prospective study involving 37 Duchenne muscular dystrophy (DMD) patients aged 8-18 years and older, we examined the impact of neurological and cardiac factors on quality of life (QoL). Our findings revealed a negative correlation between upper limb movement and overall mobility, self-service, and usual activities. Ambulatory and non-ambulatory DMD patients showed significant differences in mobility-related parameters. Cardiac evaluations demonstrated associations between mitral annular plane systolic excursion (MAPSE) and mobility-related aspects. The PEDSQL 3.0 neuromuscular model questionnaire further highlighted age-related and movement-related correlations with QoL. The loss of ambulatory status and reduced upper limb movement were negatively associated with QoL, while upper limb movement positively correlated with septal MAPSE. However, no significant associations were found between MAPSE and anxiety/depression. These findings underscore the multifaceted impact of DMD on QoL and emphasize the importance of considering both neurological and cardiac factors in comprehensive patient care.

Sonic hedgehog stimulates the recruitment of endothelial progenitor cells.

AIM: The present work focused on the Sonic hedgehog (SHH) gene that stimulates angiogenesis in the skin. It is postulated that endothelial progenitor cells (EPCs) are responsible for skin angiogenesis. The recruitment of endothelial progenitor cells was verified in the mouse skin transfected with the pSHH gene construct using the quantitative PCR method. MATERIAL AND METHODS: The tests were performed on male Balb/c mice. The SHH gene preparation was administered intradermally and/or intramuscularly. The assessment of the expression of EPCs angiogenic genes was performed using the qPCR method. The statistical analysis of the selected results was performed using the t-Student test. Differences were considered statistically significant when p<0.05. RESULTS: Studies indicate that the SHH gene administered to mouse skin as pSHH, pSHH/PEI/NaCl and pSHH/PEI/H20 formulations recruits endothelial progenitor cells to the sites of injection. The increased expression of genes specific to endothelial progenitor cells as CD34, CD44, CD133, KDR and others was observed. CONCLUSIONS: The sonic hedgehog gene stimulates the recruitment to the skin the cells expressing EPCs markers. The mechanism of proangiogenic activity of SHH is linked to EPCs mobilization. SHH gene seems to be a potential gene-candidate to proangiogenic gene therapy applications.

Gene therapy prospects--intranasal delivery of therapeutic genes.

Gene therapy is recognized to be a novel method for the treatment of various disorders. Gene therapy strategies involve gene manipulation on broad biological processes responsible for the spreading of diseases. Cancer, monogenic diseases, vascular and infectious diseases are the main targets of gene therapy. In order to obtain valuable experimental and clinical results, sufficient gene transfer methods are required. Therapeutic genes can be administered into target tissues via gene carriers commonly defined as vectors. The retroviral, adenoviral and adeno-associated virus based vectors are most frequently used in the clinic. So far, gene preparations may be administered directly into target organs or by intravenous, intramuscular, intratumor or intranasal injections. It is common knowledge that the number of gene therapy clinical trials has rapidly increased. However, some limitations such as transfection efficiency and stable and long-term gene expression are still not resolved. Consequently, great effort is focused on the evaluation of new strategies of gene delivery. There are many expectations associated with intranasal delivery of gene preparations for the treatment of diseases. Intranasal delivery of therapeutic genes is regarded as one of the most promising forms of pulmonary gene therapy research. Gene therapy based on inhalation of gene preparations offers an alternative way for the treatment of patients suffering from such lung diseases as cystic fibrosis, alpha-1-antitrypsin defect, or cancer. Experimental and first clinical trials based on plasmid vectors or recombinant viruses have revealed that gene preparations can effectively deliver therapeutic or marker genes to the cells of the respiratory tract. The noninvasive intranasal delivery of gene preparations or conventional drugs seems to be very encouraging, although basic scientific research still has to continue.