Investigation of the Possible Involvement of Retroviral Elements in ALS Teams of researchers at Columbia including Serge Przedborski, Scott Hammer, and Peter Balfe plan to assess blood and spinal fluid samples to further investigate the inappropriate activation of human endogenous retroviruses (HERVs). It is hoped that this investigation will help our scientists to understand the role of retroviral elements in ALS. Autoimmune dysfunctions have been ascribed to a number of causes, one of these; - the inappropriate activation of human endogenous retroviruses (HERVs) - is the subject of this proposal. Several groups have shown some evidence for the presence of retroviral activity in autoimmune disease, including an “MS associated” retrovirus, an Insulin dependant diabetes (IDDM) associated retrovirus and a Motor Neuron Disease associated retrovirus. A complexity arises because HERVs are an integral part of the human genome, and hence their presence is not of itself sufficient evidence for their involvement in immune dysfunction. Moreover the repertoire of HERVs present in the population and their natural levels of expression have been shown to differ more between unrelated individuals than between siblings, suggesting a large genetic component in this phenomenon. We intend to apply the published methods to a large group of ALS patients and their relatives at Columbia and thereby establish unequivocal evidence for or against this phenomenon. By using unaffected family members as controls for our assays we will be able to eliminate some of the variability associated with HERV expression, by comparisons within these families we will be able to assess whether the reported elevations of HERV expression in autoimmune dysfunction have any statistical support in the general clinical population. Participants will be ALS patients and their family members, who are cared for at Columbia’s Eleanor and Lou Gehrig MDA/ALS Research Center.