MD, PhD student Section Neuromuscular diseases
Department of Neurology and Neurosurgery
e-mail
csaris@umcutrecht.nltel +31-88 75 59111, pacer 4098
ProjectBiomarkers in Amyotrophic Lateral Sclerosis
Supervisor
L.H. Van den Berg
Aim of projectTo identify biomarkers or expression profiles in ALS patients in order to improve diagnosis and disease follow-up and to unravel molecular pathways that lead to genetic susceptibility of sporadic ALS.
SummaryAmyotrophic lateral sclerosis (ALS) is a devastating disease characterized by progressive degeneration of motor neurons in brain and spinal cord leading to muscle weakness. ALS can occur at anytime in adulthood with a median age of onset in the mid-fifties. Initial manifestations are weakness of limbs, or weakness in the bulbar region leading to abnormalities of speech, swallowing difficulties and facial weakness. Muscle weakness may be mild at first but gradually progresses and spreads to other regions of the body. The course of the disease and rate of progression varies from patient to patient. The patient eventually becomes paralyzed and approximately 50% of patients die within 3 years after onset of symptoms, usually as the result of respiratory failure. About 20% of patients survive more than 5 years.
In approximately 10% of patients, ALS occurs in families with autosomal dominant mode of inheritance. Sporadic ALS is considered a complex disease with modifying genes and environmental factors affecting its clinical expression. Several distinct molecular mechanisms may play a role in motor neuron degeneration. Blood gene expression profiling in ALS might be useful for diagnosis and prognosis, and might help to elucidate mechanisms and pathways that lead to different phenotypes in motor neuron disease.