Introduction/Aims. Primary lateral sclerosis (PLS) is exceedingly rare and has been an enigmatic disease. Recent progress has drastically changed this perception, with early biomarkers being investigated and potential medications for PLS emerging at the preclinical stage. The aim of this paper is to describe a study of PLS natural history and discuss the limitations and proposed solutions to the study of a rare and slowly progressive disease. Methods. The PLS Natural History Study is a 30-site, 24-month, prospective study that is supported by multiple funding sources. The study aims to enroll 50 early PLS (disease duration ≤4 years) and 50 definite PLS (disease duration 4 to 15 years) participants using modified PLS Diagnostic Criteria. Smartphone-based assessments including semi-quantitative and quantitative measures and patient-reported outcomes are utilized. In-person quantitative measures are also completed during site visits. The change in the PLS Functional Rating Scale score is the primary outcome. The study utilizes the NeuroBANK® patient-centric data capture and management platform. The biostatistical analysis plan has been developed. Results. In one year, 28 participants have been recruited. Enrollment has been much slower than anticipated due to the COVID-19 pandemic, the rarity of PLS, and potential study competition for internal resources from ALS clinical trials. Discussion. We discuss the need for more innovative methods to enroll and study individuals with such rare diseases and propose a number of mechanisms by which more efficient enrollment could be facilitated.
|Original language||English (US)|
|Number of pages||11|
|Journal||Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration|
|State||Published - 2023|
Bibliographical noteFunding Information:
The authors are grateful for generous support from funding agencies and Mr. David Marren and family. The authors are also deeply grateful for the participation by our patients with PLS and their families. Cassandra Talerico, PhD, Cleveland Clinic, kindly reviewed the manuscript. We also appreciate PLSNHS Publication Committee for reviewing and approval of the manuscript.
© 2022 World Federation of Neurology on behalf of the Research Group on Motor Neuron Diseases.
- PLS Functional Rating Scale (PLSFRS)
- Primary lateral sclerosis (PLS)
- clinical trials
- motor neuron disease (MND)
- natural history study
PubMed: MeSH publication types
- Journal Article
- Research Support, Non-U.S. Gov't