What is Giant Axonal Neuropahty
Giant axonal neuropathy (GAN) is a rare inherited genetic disorder that affects both the central and peripheral nervous systems. The majority of children with GAN will begin to show symptoms of the disease sometime before five years of age. Signs of GAN usually begin in the peripheral nervous system, which controls movement and sensation in the arms, legs, and other parts of the body. The typical symptoms of GAN are clumsiness and muscle weakness that progresses from a “waddling gait” to a pronounced difficulty in walking. Additional symptoms include numbness or lack of feeling in the arms and legs, seizures, and nystagmus (rapid back and forth movement of the eyes). A characteristic sign of the disease is dull, tightly curled hair that is markedly different from the parents’ in color and texture.
Researchers have discovered more than 20 different mutations associated with GAN in a gene, GAN1, which makes a protein called gigaxonin. These mutations disrupt the regulation or production of gigaxonin in the nervous system. As a result, axons, which are the long tails of neurons that allow them to communicate with other nerve cells, swell up with tangled filaments and become abnormally large. Eventually these axons deteriorate and cause problems with movement and sensation since neurons are no longer able to communicate with each other.
Doctors diagnose GAN by using several tests, including one that measures nerve conduction velocity, a brain MRI but a definitive diagnosis is only avilable from whole genone sequencing done though genetic testing.
GAN is inherited in an autosomal recessive pattern, which means that both parents of a child with GAN have to carry a copy of the mutated gene. Parents, typically, will show no signs of the disease.
Is there any treatment?
Treatment is symptomatic. Children with GAN and their families usually work with a medical team that includes a pediatric neurologist, orthopedic surgeon, physiotherapist, psychologist, and speech and occupational therapists. The major goals of treatment are to maximize physical development and minimize their deterioration as time passes.
What is the prognosis?
GAN generally progresses slowly as neurons degenerate and die. Most children have problems with walking in the early stages of the disorder. Later they may lose sensation, coordination, strength, and reflexes in their arms and legs. As time goes on, the brain and spinal cord may become involved, causing a loss of control of body movement, and seizures. Most children become wheelchair dependent in the second decade of life. Some children may survive into early adulthood.
What research is being done?
Hannah's Hope Fund has funded numerous projects over the last few years. The first in-human AAV9 viral vector clinical trial that is now ongoing at the National Institutes of Health was made possible by generous dontions to HHF. The clinical data indicates our GAN gene delivery to the central nervous system slows progression of this horrific disease and pave the way for closely related neurological disorders.
The GAN Gene Delivery Trial at NIH is showing great potential and so far 13 patients have been injected! Dr. Steven Gray of the UTSW Gene Therapy Center said it best… "None of this work would have occurred without the entire Hannah's Hope community... While we have come a long way, we have a long way to go.”
The GAN gene delivery is focused on the central nervous system. We are also working on an approach to treat the peripheral nerves of children with GAN. Newly diagnosed families around the world continue to reach out to us.
About Hannah's Hope Fund
Hannah's Hope Fund is a 501c3 public charity (Tax . #45-0593226)