In Vitro NMR Spectroscopy in Neurological Diseases (SPECMET)
The search for metabolic abnormalities in patients with neurological disorders represents an important challenge 1) to identify new potentially treatable inherited metabolic diseases, and 2) to identify biomarkers or new treatments in more common neurodegenerative or neurogenetic disorders.
This approach is currently limited by the fact that techniques aiming at identifying abnormal metabolites in human fluids (metabolomics) only detect subsets of molecules and that no general assays is available to detect abnormalities in the metabolism of complex molecules that takes place within cell organelles. As a consequence, only limited parts of the metabolism can be studied simultaneously.
The aim of this study is to evaluate whether NRM spectroscopy of body fluids (urines, cerebrospinal fluid) could allow to detect new metabolic abnormalities in patients with complex neurological diseases.
|Study Design:||Time Perspective: Prospective|
|Official Title:||Evaluation of in Vitro NMR Spectroscopy to Identify Inborn Errors of Metabolism in Patients With Complex Neurological Diseases|
- Number of patients with new metabolic diseases [ Time Frame: during the study ] [ Designated as safety issue: Yes ]
Biospecimen Retention: Samples Without DNA
urines, cerebrospinal fluid
|Study Start Date:||July 2006|
|Study Completion Date:||January 2009|
|Primary Completion Date:||July 2008 (Final data collection date for primary outcome measure)|
patients with complex neurological disease of unknown cause
positive controls : patients with already known metabolic disease for whom we already have CSF or urines
negative controls: patients with non metabolic neurological disorders of known cause hospitalized for a lumbar puncture
It is now established that most inborn errors of metabolism may present in adulthood as a neurological disorder. The diagnosis of these diseases is essential because, unlike the so-called neurodegenerative diseases, metabolic diseases are often accessible to specific treatments.
Conversely, many patients are followed for a complex neurological disease of unknown cause. We hypothesize that a significant proportion of these patients carry yet undetected inborn error of metabolism.
Recently, the use of Nuclear magnetic resonance spectroscopy (NMRS) has uncovered new metabolic diseases leading sometimes to specific treatments. However, the place of this technique in the investigation of patients with complex neurological diseases remains to be determined.
The primary goal of this project is to assess the interest of NMRS in urine and CSF to search metabolic abnormalities, not detected by conventional biochemical techniques. It is an open study. The study will be conducted in close collaboration between the neurology and genetic departments of the Pitié-Salpêtrière hospital, on the one hand and the nuclear medicine department of Poitiers in the other. 250 patients will be included over a period of 2-3 years and will be divided into 4 groups: Group 1: patients with complex neurological disease of unknown cause (200 patients) for whom urines and CSF will be collected. Group 2: positive controls (25 patients): patients with already known metabolic disease for whom we already have CSF or urines. Group 3: negative controls (25 patients): patients with non metabolic neurological disorders of known cause hospitalized for a lumbar puncture.
|Neurology department, Pitié-Salpêtrière Hospital|
|Paris, France, 75013|
|Principal Investigator:||Frederic Sedel, MD, PhD||Assistance Publique - Hôpitaux de Paris|