Giant Axonal Neuropathy
Giant axonal neuropathy is a rare neurological disorder that severely affects the peripheral and central nervous systems. Our company is dedicated to advancing the research of giant axonal neuropathy. Our experienced team of researchers and scientists tirelessly develops innovative diagnostic and therapeutic approaches to manage this debilitating disease. We are your trusted partner in giant axonal neuropathy research, providing a streamlined and comprehensive solution for all your scientific research needs.
Introduction to Giant Axonal Neuropathy
Giant axonal neuropathy is an extremely rare neurological disorder characterized by neurofilament disorder, resulting in severe impairment of neurological function. The disease is an autosomal recessive disorder that affects children and adults and causes peripheral and central nervous system abnormalities. Giant axonal neuropathy is an incredibly uncommon condition, with a mere 50 documented families reported in the existing medical literature.
Fig. 1 Shh-dependent control of Ptch abundance by gigaxonin. (Arribat, Yoan, et al., 2019)Pathogenesis of Giant Axonal Neuropathy
Giant axonal neuropathy is primarily caused by mutations in the GAN gene, which encodes the protein gigaxonin. The altered gigaxonin protein disrupts the normal organization of neurofilaments, resulting in their accumulation within the axons of neurons. Neurofilaments play a critical role in preserving the structural integrity and functionality of neurons.
The excessive buildup of neurofilaments within the axons leads to the formation of enlarged or "giant" axons. The impaired transmission of signals by these aberrant axons leads to a diverse array of neurological manifestations. Over time, the giant axons deteriorate, further exacerbating the neurological abnormalities associated with giant axonal neuropathy.
Diagnostics Development of Giant Axonal Neuropathy
Accurate and early diagnosis of giant axonal neuropathy is crucial for effective management and intervention. Significant advancements have been made in diagnostics development, enabling healthcare professionals to identify giant axonal neuropathy with greater precision.
Genetic Testing
Using targeted sequencing or whole-exome sequencing techniques is a crucial approach for identifying mutations in the GAN gene. Gene testing confirms the diagnosis of giant axonal neuropathy and aids in genetic counseling for affected individuals and their families.
Neurological Assessments
Laboratory tests such as nerve conduction studies, peripheral nerve biopsies, electromyography, and magnetic resonance imaging (MRI) can help assess the extent of nerve damage. This helps in the differential diagnosis of disease.
Therapeutics Development of Giant Axonal Neuropathy
At present, there is no known cure for giant axonal neuropathy, and therapeutic strategies primarily revolve around symptom management and enhancing the quality of life for individuals affected by the condition. Nevertheless, notable advancements have been achieved in the development of therapeutic approaches.
Gene Therapy
Gene therapy involves introducing functional copies of the GAN gene into affected cells. Viral vectors, such as adeno-associated viruses (AAVs), are commonly used to deliver the therapeutic gene. Preclinical studies in GAN animal models have shown that gene therapy can restore the expression of functional gigaxonin and prevent abnormal accumulation of neurofilaments.
Small Molecule Therapy
Researchers have identified small molecules that can modulate neurofilament assembly and disassembly. These compounds may act by stabilizing or promoting the degradation of abnormal neurofilament aggregates, preventing their accumulation within axons. Examples of such small molecules under investigation include proteasome inhibitors and autophagy inducers.
Our Services
Our company has established a comprehensive platform for developing rare disease diagnostics and therapies, encompassing small molecule drug, cell therapy, gene therapy, therapeutic antibody, therapeutic peptide, and therapeutic protein. In particular, we can provide AAV vector development services, which show significant promise for gene therapy targeting giant axonal neuropathy.
Recognizing the significance of animal disease models in the therapy development for giant axonal neuropathy, we offer our expertise in establishing mouse models specifically tailored for giant axonal neuropathy, such as Gan-/-; TgPer mouse models and GAN zebrafish models. These models serve as invaluable tools to facilitate the safety evaluation and pharmacokinetics study of your drug candidates.
Animal Models of Giant Axonal Neuropathy
| Genetically Engineered Models | |||
|---|---|---|---|
| Drawing on our proficiency in genetic engineering technologies, including CRISPR/Cas9, we have the capability to create gigaxonin gene mutant or transgenic models that faithfully mimic the pathological characteristics observed in individuals with giant axonal neuropathy. | |||
| Optional Models |
|
|
|
| Optional Species | Mice, Zebrafish, Rats, Fruit Flies, Others | ||
If you are interested in our services, please don't hesitate to contact us for more information and a detailed quotation regarding the specific services you require.
References
- Arribat, Yoan, et al. "Sonic Hedgehog repression underlies gigaxonin mutation–induced motor deficits in giant axonal neuropathy." The Journal of clinical investigation 129.12 (2019): 5312-5326.
- Nath, Banshi, and Jean-Pierre Julien. "A new mouse model of giant axonal neuropathy with overt phenotypes and neurodegeneration driven by neurofilament disorganization." Journal of Neuroscience 43.22 (2023): 4174-4189.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.