Disease Natural History and Biomarkers of SPG3A, SPG4A, and SPG31

The Neurogenetics Branch (NGB) within the National Institute of Neurological Disorders and Stroke (NINDS) is conducting a study to evaluate patients with hereditary spastic paraplegia types 3A, 4 and 31. The objective of this study is to understand disease progression in these closely related forms of hereditary spastic paraplegia using validated rating scales such as the Spastic Paraplegia Rating Scale (SPRS), and Medical Outcomes Study Questionnaire Short Form 36 Health Survey (SF-36). We also hope to develop biomarkers that could be used in future treatment trials from human serum and by utilizing transcranial magnetic stimulation (TMS) to determine central motor conduction times and resting motor thresholds. OBJECTIVES The primary objective of this protocol is to study the natural history of the most common forms of autosomal dominant hereditary spastic paraplegia. The information obtained from validated rating scales (SPRS and SF-36), TMS, and serum biomarkers, will allow for the development of treatment trials. In some cases, blood or other biologic samples (including skin biopsies) will be obtained for future laboratory studies. STUDY POPULATION The number of participants to be enrolled will be set to 300. DESIGN This is an observational study of autosomal dominant forms of hereditary spastic paraplegia progression, pathophysiology, and biomarkers. OUTCOME MEASURES In this study we will track disease progression using the Spastic Paraplegia Rating Scale (SPRS) and SF-36. Also, we will measure levels of plasma lipids, insulin, leptin, and of certain micro RNAs to investigate their utility as biomarkers. We will utilize TMS (combined with nerve conducting studies) to assess central motor conduction times (CMCT) and resting motor thresholds (RMT).