scholarly journals Development of a Disease Progression Model for Leucine‐Rich Repeat Kinase 2 in Parkinson's Disease to Inform Clinical Trial Designs

2019 ◽  
Vol 107 (3) ◽  
pp. 553-562 ◽  
Author(s):  
Malidi Ahamadi ◽  
Daniela J Conrado ◽  
Sreeraj Macha ◽  
Vikram Sinha ◽  
Julie Stone ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Clinical Trial ◽  
Parkinson's Disease ◽  
Disease Progression ◽  
Leucine Rich Repeat ◽  
Progression Model ◽  
Disease Progression Model ◽  
Clinical Trial Designs

Sleep problems affect quality of life in Parkinson's disease along disease progression

2021 ◽  
Vol 81 ◽  
pp. 307-311 ◽  
Author(s):  
Claudio Liguori ◽  
Valentino De Franco ◽  
Rocco Cerroni ◽  
Matteo Spanetta ◽  
Nicola Biagio Mercuri ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Disease Progression ◽  
Sleep Problems

scholarly journals PK/PD Modeling of the PDE7 Inhibitor—GRMS-55 in a Mouse Model of Autoimmune Hepatitis

Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 597
Author(s):  
Artur Świerczek ◽  
Hanna Plutecka ◽  
Marietta Ślusarczyk ◽  
Grażyna Chłoń-Rzepa ◽  
Elżbieta Wyska
Keyword(s):  
Mouse Model ◽  
Autoimmune Hepatitis ◽  
Disease Progression ◽  
Hepatoprotective Activity ◽  
Mechanisms Of Action ◽  
Progression Model ◽  
Adrenoceptor Agonist ◽  
Tnf Α ◽  
Disease Progression Model ◽  
Time Courses

This study aimed to assess the efficacy and explore the mechanisms of action of a potent phosphodiesterase (PDE)7A and a moderate PDE4B inhibitor GRMS-55 in a mouse model of autoimmune hepatitis (AIH). The concentrations of GRMS-55 and relevant biomarkers were measured in the serum of BALB/c mice with concanavalin A (ConA)-induced hepatitis administered with GRMS-55 at two dose levels. A semi-mechanistic PK/PD/disease progression model describing the time courses of measured biomarkers was developed. The emetogenicity as a potential side effect of the studied compound was evaluated in the α2-adrenoceptor agonist-induced anesthesia model. The results indicate that liver damage observed in mice challenged with ConA was mainly mediated by TNF-α and IFN-γ. GRMS-55 decreased the levels of pro-inflammatory mediators and the transaminase activities in the serum of mice with AIH. The anti-inflammatory properties of GRMS-55, resulting mainly from PDE7A inhibition, led to a high hepatoprotective activity in mice with AIH, which was mediated by an inhibition of pro-inflammatory signaling. GRMS-55 did not induce the emetic-like behavior. The developed PK/PD/disease progression model may be used in future studies to assess the potency and explore the mechanisms of action of new investigational compounds for the treatment of AIH.

Sign in / Sign up

Export Citation Format

Share Document