Neurophysiological studies in GM1, gangliosidosis

Abstract

Neurophysiological studies (EEG, ERG, VEP) have been carried out on 8 children with proven GM1 gangliosidosis (3 of Type I and 5 of Type II). All the EEGs were abnormal showing an increasing amount of irregular slow activity as the disease progressed. Around 2 to 3 years of age, Type II patients often showed a fluctuating 4-5 c/s rhythmic activity especially prominent in the temporal regions. Paroxysmal activity was not a conspicuous feature in any of the patients. The ERG was normal in all cases but the VEP was variably altered. The EEG/ERG/VEP findings in GM1 gangliosidosis differ from those seen in most other neurometabolic disorders of childhood.

Novel Biomarkers of Human GM1 Gangliosidosis Reflect the Clinical Efficacy of Gene Therapy in a Feline Model

“…19 EEG alterations are found in most metabolic disorders with a neurologic component, because the EEG reflects complex cerebral events. Mild EEG changes in early-stage GM1 gangliosidosis patients are reported to deteriorate suddenly, 35,36 perhaps after reaching a critical threshold of storage material or pathology. 37,38 In the current work, slowing of rhythmic activity was found in both the moderately diseased GM1 patient and the untreated GM1 cat.…”

A pentasaccharide for monitoring pharmacodynamic response to gene therapy in GM1 gangliosidosis

“…Use of non-invasive biomarkers is critical to accelerate treatment development. Numerous potential biomarkers for GM1 gangliosidosis have previously been reported 3 , 12 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 and several have been explored in the GM1 gangliosidosis cat model to assess response to therapy. 7 , 11 , 12 Of these, CSF ganglioside GM1 appeared the most promising, exhibiting more than 30-fold elevation in untreated GM1 gangliosidosis cats and reduction following AAV gene therapy treatment.…”