Giant Axonal Neuropathy Natural History Study
Giant Axonal Neuropathy Natural History Study
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.
Inclusion Criteria:

 1. Clinical diagnosis of Giant Axonal Neuropathy.

 2. Documentation of the presence of a mutation in the GAN gene as determined by gene
 sequencing from a CAP/CLIA certified laboratory or an equivalent organization.

 3. Parents or if applicable subjects must give informed consent must be capable of
 complying with the study procedures.

 4. Willing and able to comply with all protocol requirements and procedures.

 Exclusion Criteria:

 1. Unwilling or unable to travel to Columbia University Medical Center.

 2. Unstable medical condition precluding participation.

 3. Significant respiratory compromise that would interfere with safe travel to site of
 evaluation.

 4. Having a contraindication to the MRI safety requirements, including pacemaker or other
 implanted electrical device, brain stimulator, some types of dental implants, aneurysm
 clips (metal clips on the wall of a large artery), metallic prostheses (including
 metal pins and rods, heart valves, and cochlear implants), implanted delivery pump,
 shrapnel fragments, or history of claustrophobia.