Objective: In the manuscript titled “Liquid subcutaneous Levodopa-Carbidopa ND0612 effects on motor symptoms in individuals with Parkinson’s Disease: A systematic review and meta-analysis”, the objective was to con...Objective: In the manuscript titled “Liquid subcutaneous Levodopa-Carbidopa ND0612 effects on motor symptoms in individuals with Parkinson’s Disease: A systematic review and meta-analysis”, the objective was to conduct a systematic review with meta-analysis to investigate the effects ND0612 24-hour dosing regimen has on motor symptoms in individuals with Parkinson’s Disease (PD). Introduction: ND0612 is a novel minimally invasive continuous subcutaneous delivery system of liquid Levodopa-Carbidopa being investigated for the treatment of PD in individuals experiencing motor symptoms. Methods: A systematic literature search was conducted in PubMed, Cochrane, and EBSCO databases to identify randomized controlled trials investigating the effects of ND0612 on motor symptoms in individuals with PD. Outcomes included the Unified Parkinson’s Disease Rating Scale (UPDRS) Part II and Part III scores. Methodological quality was assessed using the Cochrane Grading of Recommendations Assessment, Development, and Evaluation approach. Meta-analysis was performed using a random effects model with the DerSimonian and Laird method to estimate the effects of the ND0612 24-hour dosing regimen on UPDRS Part II and Part III scores. Results: Three studies were included in our review. There were statistically significant reductions in UPDRS Part II scores (mean difference (MD) −3.299;95% confidence interval (CI) −3.438, −3.159) and in UPDRS Part III scores (MD −12.695;95% CI −24.428, −0.962) in the ND0612 24-hour dosing regimen. Results were based on very low certainty of evidence. Conclusion: Based on very low certainty evidence, the ND0612 24-hour dosing regimen is effective at improving motor symptoms in individuals with PD. Our findings suggest that ND0612 is more effective at improving UPDRS Part II and Part III scores in individuals with PD than other pharmacological and non-pharmacological treatments, warranting further study.展开更多
Parkinson’s disease is one of the most common progressive neurodegenerative disorder. It is characterized by the depletion of dopamine in the dopaminergic neurons of the striatum of the brain. Pharmacological treatme...Parkinson’s disease is one of the most common progressive neurodegenerative disorder. It is characterized by the depletion of dopamine in the dopaminergic neurons of the striatum of the brain. Pharmacological treatment involves the administration of a dopamine precursor, levodo- pa (L-Dopa), which crosses the blood-brain barrier and replaces the loss of dopamine in the brain. One of the main drawbacks of the ad- ministration of L-Dopa is its short half-life, due to the presence of enzymes, such as the amino acid decarboxylase (AADC), able to rapidly me- tabolize L-Dopa. For this reason the intake of L-Dopa takes always place together with an AADC inhibitor such as carbidopa. The assumption of carbidopa increases L-Dopa half-life, but several patients need to increase the dosage of the pharmacological therapy during the progression of the disease. Another area of dispute is represented by the possibility that L-Dopa can exert a toxic effect on the cells, both in peripheral and in central nervous system, increasing the production of ROS following its conversion to dopamine. Past studies reported toxic effects of L-Dopa in vitro and show conflicting data in in vivo experiments. More recent studies have however shown that L-dopa may exert a protective and antioxidant effect on dopaminergic cells, and its combination with carbidopa in pharmacological treatment amplifies antioxidant capability.展开更多
文摘Objective: In the manuscript titled “Liquid subcutaneous Levodopa-Carbidopa ND0612 effects on motor symptoms in individuals with Parkinson’s Disease: A systematic review and meta-analysis”, the objective was to conduct a systematic review with meta-analysis to investigate the effects ND0612 24-hour dosing regimen has on motor symptoms in individuals with Parkinson’s Disease (PD). Introduction: ND0612 is a novel minimally invasive continuous subcutaneous delivery system of liquid Levodopa-Carbidopa being investigated for the treatment of PD in individuals experiencing motor symptoms. Methods: A systematic literature search was conducted in PubMed, Cochrane, and EBSCO databases to identify randomized controlled trials investigating the effects of ND0612 on motor symptoms in individuals with PD. Outcomes included the Unified Parkinson’s Disease Rating Scale (UPDRS) Part II and Part III scores. Methodological quality was assessed using the Cochrane Grading of Recommendations Assessment, Development, and Evaluation approach. Meta-analysis was performed using a random effects model with the DerSimonian and Laird method to estimate the effects of the ND0612 24-hour dosing regimen on UPDRS Part II and Part III scores. Results: Three studies were included in our review. There were statistically significant reductions in UPDRS Part II scores (mean difference (MD) −3.299;95% confidence interval (CI) −3.438, −3.159) and in UPDRS Part III scores (MD −12.695;95% CI −24.428, −0.962) in the ND0612 24-hour dosing regimen. Results were based on very low certainty of evidence. Conclusion: Based on very low certainty evidence, the ND0612 24-hour dosing regimen is effective at improving motor symptoms in individuals with PD. Our findings suggest that ND0612 is more effective at improving UPDRS Part II and Part III scores in individuals with PD than other pharmacological and non-pharmacological treatments, warranting further study.
文摘Parkinson’s disease is one of the most common progressive neurodegenerative disorder. It is characterized by the depletion of dopamine in the dopaminergic neurons of the striatum of the brain. Pharmacological treatment involves the administration of a dopamine precursor, levodo- pa (L-Dopa), which crosses the blood-brain barrier and replaces the loss of dopamine in the brain. One of the main drawbacks of the ad- ministration of L-Dopa is its short half-life, due to the presence of enzymes, such as the amino acid decarboxylase (AADC), able to rapidly me- tabolize L-Dopa. For this reason the intake of L-Dopa takes always place together with an AADC inhibitor such as carbidopa. The assumption of carbidopa increases L-Dopa half-life, but several patients need to increase the dosage of the pharmacological therapy during the progression of the disease. Another area of dispute is represented by the possibility that L-Dopa can exert a toxic effect on the cells, both in peripheral and in central nervous system, increasing the production of ROS following its conversion to dopamine. Past studies reported toxic effects of L-Dopa in vitro and show conflicting data in in vivo experiments. More recent studies have however shown that L-dopa may exert a protective and antioxidant effect on dopaminergic cells, and its combination with carbidopa in pharmacological treatment amplifies antioxidant capability.
