Intrathecal Administration of scAAV9/JeT-GAN for the Treatment of Giant Axonal Neuropathy

Gene Transfer Clinical Trial

Official title: A Phase I Study of Intrathecal Administration of scAAV9/JeT-GAN for the Treatment of Giant Axonal Neuropathy

Status Active, not recruiting

Clinical Trial Summary

Title: Intrathecal Administration of scAAV9/JeT-GAN for the Treatment of Giant Axonal Neuropathy Background: - The Gigaxonin gene lets the body make a protein chemical called Gigaxonin. Nerves need Gigaxonin to work properly. Giant Axonal Neuropathy (GAN) causes a shortage of functional Gigaxonin. Nerves stop working normally in people with GAN. This causes problems with walking and sometimes with eating, breathing, and many other activities. GAN has no cure. Over time, GAN can shorten a person s life. Researchers want to see if a gene transfer treatment may help people with GAN. Objectives: - To see if a gene transfer is safe and shows potential to help people with GAN. Eligibility: - People age 3 and older with GAN. Design: - For 1 month following gene transfer participants must live full-time within 100 miles of the NIH. - Participants will be screened by phone and in person. They will take many tests. Some are listed below. Their medical records will be reviewed. Their caregivers may be contacted. - Participants will have a total of about 27 visits, weekly, monthly, and then yearly over 15 years. They will include many of the tests below. - Physical and nervous system exams. - Blood, urine, and stool samples. - Nerve, lung, heart, and eye tests. - Questionnaires. - MRI scans, nerve biopsies, and spinal taps. Participants will be sedated for some tests. - Speech, memory, muscle, and mobility tests. - Skin biopsy (small sample removed). - Participants will take many medicines. Some require intravenous lines. - Participants will get the gene transfer through an injection by spinal tap into their cerebrospinal fluid, which flows around the brain and spinal cord. The genes are packed in a modified virus that carries the genes to cells in their body. Participants safety is not guaranteed.

Clinical Trial Description

This is an open-label and non-randomized first-in-human (Phase 1) clinical trial which incorporates an escalating single dose paradigm to assess safety of the gene transfer vector scAAV9/JeT-GAN administered intrathecally to target the brain and spinal cord of individuals with genetically confirmed Giant Axonal Neuropathy. GAN is a chronic neurodegenerative autosomal recessive disease pathologically characterized by enlarged axons with disordered intermediate filaments and microtubules. The disease pathology is due to loss-of-function variants in the GAN gene, which encodes the protein gigaxonin. Gigaxonin plays a major role in the maintenance of orderly and functional intermediate filament (IF) architecture, which is critical for axonal function. Onset of symptoms, usually at three to four years of age, generally manifests with a clumsy and unsteady gait (sensory ataxia). In the peripheral nervous system, the disease progressively affects predominantly sensory and motor nerves. By the end of the second decade of life, patients typically are wheelchair dependent with limited use of the arms and little to no use of their legs. During the second decade a tracheostomy or other means of ventilation, as well as a feeding tube, are often necessary. Death normally occurs in the second or third decade of life. We recently identified a sub-cohort of patients with a milder and later onset, yet progressive form of GAN characterized by a prolonged preservation of ambulation and less extensive white matter changes on brain MRI restricted to the infratentorial regions. These individuals are good trial candidates given the increased prospect of benefit at milder disease stages. There are no statistics on the incidence of GAN, but it is considered extremely rare and does not have an approved treatment aside from supportive care. Intrathecal delivery of a gene transfer vector carrying a normal copy of the GAN to the spinal cord and brain offers a potentially effective treatment for GAN. ;

Related Conditions & MeSH terms

• Gene Transfer
• Giant Axonal Neuropathy
• Peripheral Nervous System Diseases

• NCT number: NCT02362438
• Study type: Interventional
• Source: Taysha Gene Therapies, Inc.
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: April 24, 2015
• Completion date: April 1, 2035