Historically my group has been involved in autoimmune disorders of the peripheral nervous system, in particular the Lambert-Eaton myasthenic syndrome (LEMS). LEMS is characterised by muscle weakness and fatigability and, in around 60% of cases, is found in association with small cell carcinoma of the lung (SCLC), an aggressive carcinoma of neuroendocrine origin that strongly associates with smoking. Autoantibodies to a particular subtype (P/Q) of voltage-gated calcium channel (VGCC) have been detected in the sera of greater than 90% of LEMS patients. It has been shown that the SCLC express voltage-gated calcium channels (VGCC) on the surface and it is thought that antibodies initially raised against these VGCC cross-react with channels at the neuromuscular junction resulting in the muscle weakness observed, the aetiology of the disease in the 40% of LEMS patients without carcinoma is unknown.
Currently my group is investigating the possibility that certain forms of epilepsies may have an autoimmune aetiology. We have detected autoantibodies to voltage-gated potassium channels (VGKC), NMDA-receptors and glycine-receptors in a subset of patients who have seizures with acute or subacute encephalopathic disorder. Additionally we have detected antibodies to glutamic acid decarboxylase (GAD) in some patients with temporal lobe epilepsy and antibodies to the alpha7 neuronal acetylcholine receptor in the sera of two patients with Rasmussen's encephalitis. We are currently investigating whether these autoantibodies are pathogenic and the mechanism whereby the antibodies can cross the blood brain barrier. The group is also investigating whether opsoclonus-myoclonus syndrome (dancing-eye syndrome) another severe CNS disorder that effects young children and is often associated with the presence of a neuroblastoma, may also have an autoimmune origin
Awards Training and Qualifications
- 1972- 1975 BSc (Hons), University College, London
- 1975- 1979 PhD, Imperial College, London
Autoantibodies to glutamic acid decarboxylase in patients with epilepsy and their relationship with type 1 diabetes: a pilot study.
Moloney TC. et al, (2016), J Neurol Neurosurg Psychiatry, 87, 676 - 677
Antibodies to AMPA receptors in Rasmussen's encephalitis.
Nibber A. et al, (2016), Eur J Paediatr Neurol, 20, 222 - 227
Clinical relevance of voltage-gated potassium channel–complex antibodies in children.
Hacohen Y. et al, (2015), Neurology, 85, 967 - 975
Paraneoplastic neurologic disorders in small cell lung carcinoma: A prospective study.
Gozzard P. et al, (2015), Neurology, 85, 235 - 239
MOG cell-based assay detects non-MS patients with inflammatory neurologic disease.
Waters P. et al, (2015), Neurol Neuroimmunol Neuroinflamm, 2