A Disease Progression Model to Quantify the Nonmotor Symptoms of Parkinson’s Disease in Participants With Leucine‐Rich Repeat Kinase 2 Mutation
| Autor: | Caroline H. Williams-Gray, Diane Stephenson, Klaus Romero, Judith Anton, Ferdous Gheyas, Nathan J. Hanan, Jonas Weidemann, Minhua Yang, Malidi Ahamadi, Massimo Bani, Bob Stafford, Charles S. Venuto, Chao Chen, Vincent Thuillier, Ka Lai Yee, Gennaro Pagano, Monica Javidnia, Sreeraj Macha, Nitin Mehrotra, Vikram Sinha, Kenneth Marek, Yaming Hang, Hans Smit, Anne Pedata, Mussie Akalu, Babak Boroojerdi, David T. Dexter, Glenn T. Stebbins |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Adult
Male Oncology Heterozygote medicine.medical_specialty Parkinson's disease Databases Factual Disease Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 medicine.disease_cause Severity of Illness Index 030226 pharmacology & pharmacy Antiparkinson Agents 03 medical and health sciences 0302 clinical medicine Predictive Value of Tests Rating scale Internal medicine medicine Humans Pharmacology (medical) Longitudinal Studies Aged Aged 80 and over Pharmacology Mutation business.industry Kinase Therapeutic effect Age Factors Parkinson Disease Middle Aged Models Theoretical medicine.disease LRRK2 Confidence interval nervous system diseases 030220 oncology & carcinogenesis Disease Progression alpha-Synuclein Glucosylceramidase Female business |
| Zdroj: | Clinical Pharmacology & Therapeutics. 110:508-518 |
| ISSN: | 1532-6535 0009-9236 |
| Popis: | Leucine-rich repeat kinase 2 (LRRK2) inhibitors are currently in clinical development as interventions to slow progression of Parkinson's disease (PD). Understanding the rate of progression in PD as measured by both motor and non-motor features is particularly important in assessing the potential therapeutic effect of LRRK2 inhibitors in clinical development. Using standardized data from the Critical Path for Parkinson's Unified Clinical Database, we quantified the rate of progression of the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part I (non-motor aspects of experiences of daily living) in 158 PD participants who were carriers and 598 PD participants who were non-carriers of at least one of three different LRRK2 gene mutations (G2019S, R1441C/G, R1628P). Age and disease duration were found to predict baseline disease severity, while presence of at least one of these three LRRK2 mutations was a predictor of the rate of MDS-UPDRS Part I progression. The estimated progression rate in MDS-UPDRS Part I was 0.648 (95% confidence interval: 0.544, 0.739) points per year in non-carriers of a LRRK2 mutation and 0.259 (95% confidence interval: 0.217, 0.295) points per year in carriers of a LRRK2 mutation. This analysis demonstrates that the rate of progression based on MDS-UPDRS Part I is approximately 60% lower in carriers as compared to non-carriers of LRRK2 gene mutations. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text