Giant Axonal Neuropathy Natural History Study

Overview

Giant Axonal Neuropathy (GAN) is a devastating and rare childhood disease. Children with GAN develop increasing muscle weakness, impaired sensation, and at times mental retardation. GAN starts in infancy, leads to significant disability, and typically leads to death within the first 30 years of life. GAN is caused by a defect in the "gigaxonin" (GAN) gene, resulting in pathologically enlarged and dysfunctional nerves. Currently, there is no effective therapy. To find out what medications can help patients with GAN, the investigators have to conduct clinical trials. In this study, the investigators propose to prepare for future clinical trials and will invite GAN patients to join our research effort. The investigators will examine them regularly to better understand their disease. The visits will include questions, a physical exam, blood drawing, a lumbar puncture, and a skin biopsy. The visits will also include tests that assess the electrical conductivity of the patients' nerves as well as a test to measure the patients' brain wave activity. In addition, the investigators will be performing tests to evaluate the patients' motor function, their vision, and thinking ability. Identifying an effective GAN treatment is very important because there is currently none. Clinical trials are the only way to decide whether a new treatment works in GAN patients or not. With the future objective of conducting clinical trials in GAN, the proposed project has three specific aims. The first is to plan for clinical trials by developing reliable outcome measures, and establishing the infrastructure needed to carry out efficient clinical trials. The second is to further characterize the patient population from a clinical and molecular point of view, and the third aim is to utilize the information gathered in this study to further pre-clinical GAN drug development to select candidate drugs.

Giant Axonal Neuropathy (GAN) is a rare autosomal recessive neurodegenerative disorder that appears during childhood and affects both the central and peripheral nervous systems. This disorder is generally characterized by motor and sensory involvement including progressive and predominant distal clumsiness, muscle weakness, and pronounced gait disturbances. GAN is caused by various mutations in the GAN gene that encodes the protein gigaxonin. This leads to giant axonal swelling and degeneration due to substantial accumulation of neurofilaments in the axon. Currently, there is no effective therapy, with onset occurring before the age of seven, and death usually occurring between the first and third decade of life.