neurofilament light- chain in ataxia telangiectasia

Conditions: Ataxia Telangiectasia

Summary: ataxia telangiectasia (a-t) is a rare autosomal recessive neurodegenerative disorder characterized by progressive cerebellar ataxia, immunodeficiency, chromosomal instability, and cancer susceptibility. currently there are no curative therapy options. the clinical presentation of the disease has a wide variety is linked to the proven mutation, immunological status and residual atm kinase activity. apart from these prognostic markers, hardly any biomarker to predict disease course is available. aim of the present proposal is to evaluate serum concentrations of neurofilament - light chain in the serum of whole blood as biomarker of neurodegeneration prospectively. in addition to that, the investigators will examine the evolution of neurofilament - light chain longitudinally by blood samples from our biobank as well as the concentration of neurofilament - light chain in cerebrospinal fluid (csf) of affected a-t patients from our biobank. as in other neurodegenerative disorders and ataxias, the investigators expect that neurofilament- light chain levels are increased in the a-t cohort and correlated to the neurological status of a-t patients evaluated by means of at-score.

a-t is a neurodegenerative disease with mutation in the atm gene. the clinical presentation is complex and affects many different organ systems. typical findings are progressive cerebellar ataxia, malnutrition, immunodeficiency, chromosomal instability and cancer susceptibility. in addition, new disease entities such as hepatopathy, diabetes and endocrinological alterations are coming to the force. the severity of the disease is closely related to presence of residual kinase activity, immunological status and specific mutations. however, the individual course of the disease is hard to predict. there is an urgent need to find and define reliable biomarkers for disease progression in order to estimate the prognosis of individual disease course. according the classification of estimated disease severity, the most suitable therapy and support can be organized. in many other neurodegenerative disorders neurofilament- light chain has been reported to be a sensitive and reproducable serum biomarker for disease progression, activity and monitoring of therapy efficaciousness. neurofilament proteins indicate neuroaxonal damage independent of causal pathway, the advantage of neurofilaments as a biomarker of disease progression is that levels rise upon neuroaxonal damage not only in csf but also in blood. therefore, they can be used to monitor disease activity without invasive procedures. the aim of the proposal is to measure and evaluate neurofilament-light chain as serum biomarker of disease progression in a-t patients. additionally, the investigators will measure neurofilament-light chain in csf from their human biobank and characterize the individual evolution in the serum of whole blood taken from the biobank. in the prospective part of the study, the investigators will correlate the levels of neurofilament to a-t scores for neurological assessment.

Eligibility criteria:
inclusion criteria: * informed consent * patients: aged ≥2 and 45 years * known a-t exclusion criteria: * cranial trauma in the last 6 months * ongoing malignant disease * chronic diseases or infections (e.g. hiv, tbc) * pregnancy * alcohol, substance or drug abuse * inability to capture extend and consequences of the study

Keywords: ataxia telangiectasia neurodegeneration biomarker disease progression csf neurofilament light chain