چکیده:
Purpose of the study: Alzheimer's disease is missing proven disease-modifying therapies; Mesenchymal stem cell-derived conditioned medium (MSC-CM) provides a without using living cells anti-inflammatory and neuroprotective strategy. This phase 1 trial examined how safe and acceptable it is to administer intranasal Wharton's jelly MSC-CM in mild-to-moderate AD.
Methods: We designed a phase trial that was open-label, single-arm; nine patients (4 males, 5 females; aged 65-89) with mild-to-moderate AD took part. Participants received intranasal WJMSC-CM at escalating s (1.2, 1.8 and 3.0 mL/day) over three consecutive days. Daily vital signs, physical checks and adverse checks were conducted to assess adverse. Baseline and 3-month brain MRI were used to test structural neuroanatomical safety. The baseline and day 4 serum biomarkers (IL-1β, IL-6, TNF-α, CRP, TGF-β, BDNF) were quantitatively determined by ELISA. The MMSE, MoCA, ADL, and IADL scales were used to assess cognitive and functional statuses.
Results: All nine patients finished both parts of the study. No major side effects or neuroimaging abnormalities were found. The side effects of two people in the medium group were mild and temporary-cough and tingling of the lips- went away on their own. No significant decrease in pro-inflammatory cytokines was found from serum biomarker analysis (IL-6, TNF-α, IL-1β, CRP; p > 0.05). Interestingly, BDNF levels increased significantly (p = 0.01), mainly in the low- cohort. Although this study was not powered to prove efficacy, exploratory analyses indicated numerical improvements for the treatment group. There was a trend for improvement in cognitive and functional scores during follow up. The results of this study should be interpreted with care, as they may be hypotheses under test and need to be confirmed by properly powered studies.
Conclusion: After the experiments, we determined that the WJMSC-CM could be safely administered via the nasal route. Patients with mild and moderate Alzheimer's had no major problems with it. These initial results indicate possible biological activity and warrant further investigation. Further investigation in larger RCTs to assess clinical efficacy.
Methods: We designed a phase trial that was open-label, single-arm; nine patients (4 males, 5 females; aged 65-89) with mild-to-moderate AD took part. Participants received intranasal WJMSC-CM at escalating s (1.2, 1.8 and 3.0 mL/day) over three consecutive days. Daily vital signs, physical checks and adverse checks were conducted to assess adverse. Baseline and 3-month brain MRI were used to test structural neuroanatomical safety. The baseline and day 4 serum biomarkers (IL-1β, IL-6, TNF-α, CRP, TGF-β, BDNF) were quantitatively determined by ELISA. The MMSE, MoCA, ADL, and IADL scales were used to assess cognitive and functional statuses.
Results: All nine patients finished both parts of the study. No major side effects or neuroimaging abnormalities were found. The side effects of two people in the medium group were mild and temporary-cough and tingling of the lips- went away on their own. No significant decrease in pro-inflammatory cytokines was found from serum biomarker analysis (IL-6, TNF-α, IL-1β, CRP; p > 0.05). Interestingly, BDNF levels increased significantly (p = 0.01), mainly in the low- cohort. Although this study was not powered to prove efficacy, exploratory analyses indicated numerical improvements for the treatment group. There was a trend for improvement in cognitive and functional scores during follow up. The results of this study should be interpreted with care, as they may be hypotheses under test and need to be confirmed by properly powered studies.
Conclusion: After the experiments, we determined that the WJMSC-CM could be safely administered via the nasal route. Patients with mild and moderate Alzheimer's had no major problems with it. These initial results indicate possible biological activity and warrant further investigation. Further investigation in larger RCTs to assess clinical efficacy.
نوع مطالعه: Original |
موضوع مقاله:
Cellular and molecular Neuroscience
دریافت: 1405/2/19 | پذیرش: 1405/6/10
دریافت: 1405/2/19 | پذیرش: 1405/6/10
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