BACKGROUND: Mesenchymal stromal cells (MSCs) have potent immunomodulatory and neuroprotective properties, and have been tested in neurodegenerative diseases resulting in meaningful clinical improvements. Regulatory guidelines specify the need to perform preclinical studies prior any clinical trial, including biodistribution assays and tumourigenesis exclusion. We conducted a preclinical study of human bone marrow MSCs (hBM-MSCs) injected by intrathecal route in Non-Obese Diabetic Severe Combined Immunodeficiency mice, to explore cellular biodistribution and toxicity as a privileged administration method for cell therapy in Friedreich's Ataxia. METHODS: For this purpose, 3 × 10⁵ cells were injected by intrathecal route in 12 animals (experimental group) and the same volume of culture media in 6 animals (control group). Blood samples were collected at 24 h (n = 9) or 4 months (n = 9) to assess toxicity, and nine organs were harvested for histology and safety studies. Genomic DNA was isolated from all tissues, and mouse GAPDH and human β2M and β-actin genes were amplified by qPCR to analyze hBM-MSCs biodistribution. RESULTS: There were no deaths nor acute or chronic toxicity. Hematology, biochemistry and body weight were in the range of normal values in all groups. At 24 h hBM-MSCs were detected in 4/6 spinal cords and 1/6 hearts, and at 4 months in 3/6 hearts and 1/6 brains of transplanted mice. No tumours were found. CONCLUSION: This study demonstrated that intrathecal injection of hBM-MSCs is safe, non toxic and do not produce tumors. These results provide further evidence that hBM-MSCs might be used in a clinical trial in patients with FRDA.
Animals ; Biochemistry ; Body Weight ; Bone Marrow ; Brain ; Cell- and Tissue-Based Therapy ; Culture Media ; DNA ; Friedreich Ataxia ; Heart ; Hematology ; Humans ; Injections, Spinal ; Mesenchymal Stromal Cells ; Methods ; Mice ; Neurodegenerative Diseases ; Neuroprotection ; Reference Values ; Severe Combined Immunodeficiency ; Spinal Cord

Background: Gait speed is associated with a higher prevalence of balance disorders in older adults residing at high altitudes. This study investigated this association in older adults from 12 high-altitude Andean Peruvian communities. Methods: We performed a secondary data analysis from an analytical cross-sectional study of adults >60 years of age, residing in 12 high-altitude Andean Peruvian communities, enrolled between 2013 and 2019. The exposure and outcome variables were gait speed (categorized in tertiles), and balance disorders (defined as a functional reach value of ≤20.32 cm), respectively. We built generalized linear models of the Poisson family with a logarithmic link function and robust variances, and estimated crude prevalence ratios (cPR) and adjusted prevalence ratios (aPR) with 95% confidence intervals (CIs). Results: We analyzed 418 older adults; 38.8% (n=162) were male, and the mean age was 73.2±6.9 years. The mean gait speed and functional reach were 0.66±0.24 m/s and 19.9±6.48 cm, respectively. In the adjusted regression model, the intermediate (aPR=1.88; 95% CI, 1.39–2.55; p<0.001) and low (aPR=2.04; 95% CI, 1.51–2.76; p<0.001) tertiles of gait speed were associated with a higher prevalence of balance disorders. Conclusion The intermediate and low tertiles of gait speed were associated with a higher prevalence of balance disorders among older adult residents of 12 high-altitude Andean communities. We recommend further research on the behavior of this association to propose interventions for these vulnerable groups and reduce the impact of geriatric conditions.

Background: Gait speed is associated with a higher prevalence of balance disorders in older adults residing at high altitudes. This study investigated this association in older adults from 12 high-altitude Andean Peruvian communities. Methods: We performed a secondary data analysis from an analytical cross-sectional study of adults >60 years of age, residing in 12 high-altitude Andean Peruvian communities, enrolled between 2013 and 2019. The exposure and outcome variables were gait speed (categorized in tertiles), and balance disorders (defined as a functional reach value of ≤20.32 cm), respectively. We built generalized linear models of the Poisson family with a logarithmic link function and robust variances, and estimated crude prevalence ratios (cPR) and adjusted prevalence ratios (aPR) with 95% confidence intervals (CIs). Results: We analyzed 418 older adults; 38.8% (n=162) were male, and the mean age was 73.2±6.9 years. The mean gait speed and functional reach were 0.66±0.24 m/s and 19.9±6.48 cm, respectively. In the adjusted regression model, the intermediate (aPR=1.88; 95% CI, 1.39–2.55; p<0.001) and low (aPR=2.04; 95% CI, 1.51–2.76; p<0.001) tertiles of gait speed were associated with a higher prevalence of balance disorders. Conclusion The intermediate and low tertiles of gait speed were associated with a higher prevalence of balance disorders among older adult residents of 12 high-altitude Andean communities. We recommend further research on the behavior of this association to propose interventions for these vulnerable groups and reduce the impact of geriatric conditions.

Background: Gait speed is associated with a higher prevalence of balance disorders in older adults residing at high altitudes. This study investigated this association in older adults from 12 high-altitude Andean Peruvian communities. Methods: We performed a secondary data analysis from an analytical cross-sectional study of adults >60 years of age, residing in 12 high-altitude Andean Peruvian communities, enrolled between 2013 and 2019. The exposure and outcome variables were gait speed (categorized in tertiles), and balance disorders (defined as a functional reach value of ≤20.32 cm), respectively. We built generalized linear models of the Poisson family with a logarithmic link function and robust variances, and estimated crude prevalence ratios (cPR) and adjusted prevalence ratios (aPR) with 95% confidence intervals (CIs). Results: We analyzed 418 older adults; 38.8% (n=162) were male, and the mean age was 73.2±6.9 years. The mean gait speed and functional reach were 0.66±0.24 m/s and 19.9±6.48 cm, respectively. In the adjusted regression model, the intermediate (aPR=1.88; 95% CI, 1.39–2.55; p<0.001) and low (aPR=2.04; 95% CI, 1.51–2.76; p<0.001) tertiles of gait speed were associated with a higher prevalence of balance disorders. Conclusion The intermediate and low tertiles of gait speed were associated with a higher prevalence of balance disorders among older adult residents of 12 high-altitude Andean communities. We recommend further research on the behavior of this association to propose interventions for these vulnerable groups and reduce the impact of geriatric conditions.

Background: Gait speed is associated with a higher prevalence of balance disorders in older adults residing at high altitudes. This study investigated this association in older adults from 12 high-altitude Andean Peruvian communities. Methods: We performed a secondary data analysis from an analytical cross-sectional study of adults >60 years of age, residing in 12 high-altitude Andean Peruvian communities, enrolled between 2013 and 2019. The exposure and outcome variables were gait speed (categorized in tertiles), and balance disorders (defined as a functional reach value of ≤20.32 cm), respectively. We built generalized linear models of the Poisson family with a logarithmic link function and robust variances, and estimated crude prevalence ratios (cPR) and adjusted prevalence ratios (aPR) with 95% confidence intervals (CIs). Results: We analyzed 418 older adults; 38.8% (n=162) were male, and the mean age was 73.2±6.9 years. The mean gait speed and functional reach were 0.66±0.24 m/s and 19.9±6.48 cm, respectively. In the adjusted regression model, the intermediate (aPR=1.88; 95% CI, 1.39–2.55; p<0.001) and low (aPR=2.04; 95% CI, 1.51–2.76; p<0.001) tertiles of gait speed were associated with a higher prevalence of balance disorders. Conclusion The intermediate and low tertiles of gait speed were associated with a higher prevalence of balance disorders among older adult residents of 12 high-altitude Andean communities. We recommend further research on the behavior of this association to propose interventions for these vulnerable groups and reduce the impact of geriatric conditions.

Background: and Purpose Visual hallucinations (VH) and subjective cognitive complaints (SCC) are associated with cognitive impairment (CI) in Parkinson’s disease. Our aims were to determine the association between VH and SCC and the risk of CI development in a cohort of patients with Parkinson’s disease and normal cognition (PD-NC). Methods: Patients with PD-NC (total score of >80 on the Parkinson’s Disease Cognitive Rating Scale [PD-CRS]) recruited from the Spanish COPPADIS cohort from January 2016 to November 2017 were followed up after 2 years. Subjects with a score of ≥1 on domain 5 and item 13 of the Non-Motor Symptoms Scale at baseline (V0) were considered as “with SCC” and “with VH,” respectively. CI at the 2-year follow-up (plus or minus 1 month) (V2) was defined as a PD-CRS total score of <81. Results: At V0 (n=376, 58.2% males, age 61.14±8.73 years [mean±SD]), the frequencies of VH and SCC were 13.6% and 62.2%, respectively. VH were more frequent in patients with SCC than in those without: 18.8% (44/234) vs 4.9% (7/142), p<0.0001. At V2, 15.2% (57/376) of the patients had developed CI. VH presenting at V0 was associated with a higher risk of CI at V2 (odds ratio [OR]=2.68, 95% confidence interval=1.05–6.83, p=0.039) after controlling for the effects of age, disease duration, education, medication, motor and nonmotor status, mood, and PD-CRS total score at V0. Although SCC were not associated with CI at V2, presenting both VH and SCC at V0 increased the probability of having CI at V2 (OR=3.71, 95% confidence interval=1.36–10.17, p=0.011). Conclusions VH were associated with the development of SCC and CI at the 2-year follow-up in patients with PD-NC.