Establishing the Natural History of Upper Motor Neurondominant ALS and PLS

The proposed study will change the current perception of PLS as a rare and neglected motor neuron disease. Multiple ALS study sites, at least more than 25 sites in the USA, will collaborate to investigate how fast the disease progresses in PLS. The study will include a number of quantitative clinical measurements, including tests that detect changes of upper motor neuron dysfunction and a functional scale specifically designed for PLS called the PLSFRS. The PLSFRS has been specifically developed to detect clinical changes in PLS, which tend to develop slowly. We will also make a biorepository for future biomarker development. We will investigate EMG changes to detect any development of lower motor neuron dysfunction. We will study 50 early PLS cases (those who developed the disease less than 4 years after symptom onset) and 50 well-established PLS cases (those who have been diagnosed as definite PLS for more than 4 years but less than 15 years after symptom onset). We will analyze how the disease progresses among these cases. We currently lack any reliable data for future clinical trials. Unless we have such data, we will not know how many patients need to be enrolled to conduct effective and efficient clinical trials in the future. Furthermore, our study will evaluate the accuracy and reliability of the diagnoses based on the new diagnostic criteria. This is the first comprehensive study of its kind that will investigate the natural history of PLS. After this study, we will be able to design future clinical trials effectively. In fact, in the past few years, possible medications for PLS have become available. We believe that this study will the beginning of active clinical trials in PLS.