Effect of levodopa/carbidopa on the progression of Machado-Joseph disease /spinocerebellar ataxia type 3 (MJD/SCA3) DOI Creative Commons

Mafalda Raposo,

Zsuzsa Sárkány,

Joana Damásio

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 3, 2024

Background and Objectives In Machado-Joseph disease or spinocerebellar ataxia type 3 (MJD/SCA3), ataxin-3 accumulates as neuronal nuclear inclusions in specific regions of the brain such substantia nigra dentate cerebellar nucleus. Ataxin-3 aggregation is strongly inhibited by dopamine, a neurotransmitter whose levels can be increased through use medication containing levodopa/carbidopa (LA/CA). Here we perform retrospective study to determine whether exposition LA/CA associated with decreased progression MJD/SCA3. Methods We assessed natural history individuals MJD/SCA3 also SCA1, 2, 6, 7, 8, 10 enrolled Clinical Research Consortium for Spinocerebellar Ataxias (CRC-SCA). Our initial analysis focused on all ataxias (SCAs) was Scale Assessment Rating Ataxia (SARA) between 2010 2023. To account important covariates affecting time evolution SARA scores, our then limited cases genetic age information available. A linear mixed model used effects other anti-parkinsonian drugs at 6 13 years progression. Results Among group 716 SCAs monitored 58 (8.1%) had taken formulations, whereas 26 (3.6%) drugs, mainly dopamine receptor agonists. non-parametric suggested positive effect probability major decline during patient monitoring. multivariate 262 (of which 30 were LA/CA) showed statistically significant favor exposition: after adjusting number CAG repeats expanded allele, yearly response demonstrated (linear coefficient β = −0.651 [95% confidence interval −1.141 −0.161 ], P 0.009 ) ( −0.274 [ −0.547 −0.002 0.048 ). Conclusions The treat non-cerebellar symptoms beneficial score This observation supports hypothesis that restoring brains patients might slow down findings warrant further investigation MJD/SCA3, even absence Parkinsonian should treated what doses.

Language: Английский

Antisense Oligonucleotides: A Promising Advancement in Neurodegenerative Disease Treatment DOI

Katarzyna Dudzisz,

Ilona Wandzik

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 177644 - 177644

Published: April 1, 2025

Language: Английский

Citations

0
Trehalose ameliorates severe acute pancreatitis by modulating the gut microbial metabolism DOI

Weiqin Li,

Haibin Hao,

Deren Du

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Abstract Severe Acute Pancreatitis (SAP) is an acute, severe, and high-mortality special type of pancreatitis, often accompanied by gut microbiota disorders. Gut its derived metabolites are involved in SAP progression, but microbial metabolism their roles remain unclear. In this study, we found that homeostasis was imbalanced SAP, especially the increase lipids decrease carbohydrate & amino acid metabolism, which were reversed depleting microbiota. Trehalose significantly increased after Interestingly, oral trehalose effectively reduced pancreatic injury ameliorated SAP-induced imbalance increasing decreasing galactose metabolism. The role shown to be dependent on via FMT, inhibition Lactobacillaceae expansion Muribaculaceae. Mechanistically, trehalose-remodeled increases serum TG, IL-6, IL-17A, TNF-α, inhibited caspase-3-mediated apoptosis macrophage infiltration pancreas. Overall, our study revealed ameliorates modulating homeostasis, provides new insights into alterations “microbial metabolism-gut-pancreatic axis” treat diseases.

Language: Английский

Citations

1
Examples of diseases where appropriate therapies were discovered DOI

Moyra Smith

Elsevier eBooks, Journal Year: 2024, Volume and Issue: unknown, P. 209 - 262

Published: Nov. 1, 2024

Language: Английский

Citations

0
Therapies that address altered gene regulation DOI

Moyra Smith

Elsevier eBooks, Journal Year: 2024, Volume and Issue: unknown, P. 263 - 292

Published: Nov. 1, 2024

Language: Английский

Citations

0
Effect of levodopa/carbidopa on the progression of Machado-Joseph disease /spinocerebellar ataxia type 3 (MJD/SCA3) DOI Creative Commons

Mafalda Raposo,

Zsuzsa Sárkány,

Joana Damásio

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 3, 2024

Background and Objectives In Machado-Joseph disease or spinocerebellar ataxia type 3 (MJD/SCA3), ataxin-3 accumulates as neuronal nuclear inclusions in specific regions of the brain such substantia nigra dentate cerebellar nucleus. Ataxin-3 aggregation is strongly inhibited by dopamine, a neurotransmitter whose levels can be increased through use medication containing levodopa/carbidopa (LA/CA). Here we perform retrospective study to determine whether exposition LA/CA associated with decreased progression MJD/SCA3. Methods We assessed natural history individuals MJD/SCA3 also SCA1, 2, 6, 7, 8, 10 enrolled Clinical Research Consortium for Spinocerebellar Ataxias (CRC-SCA). Our initial analysis focused on all ataxias (SCAs) was Scale Assessment Rating Ataxia (SARA) between 2010 2023. To account important covariates affecting time evolution SARA scores, our then limited cases genetic age information available. A linear mixed model used effects other anti-parkinsonian drugs at 6 13 years progression. Results Among group 716 SCAs monitored 58 (8.1%) had taken formulations, whereas 26 (3.6%) drugs, mainly dopamine receptor agonists. non-parametric suggested positive effect probability major decline during patient monitoring. multivariate 262 (of which 30 were LA/CA) showed statistically significant favor exposition: after adjusting number CAG repeats expanded allele, yearly response demonstrated (linear coefficient β = −0.651 [95% confidence interval −1.141 −0.161 ], P 0.009 ) ( −0.274 [ −0.547 −0.002 0.048 ). Conclusions The treat non-cerebellar symptoms beneficial score This observation supports hypothesis that restoring brains patients might slow down findings warrant further investigation MJD/SCA3, even absence Parkinsonian should treated what doses.

Language: Английский

Citations

0