Neurodegeneration with Brain Iron Accumulation (NBIA)
Neurodegeneration with brain iron accumulation (NBIA) is a rare, inherited neurodegenerative disease. NBIA is a term that covers a broader spectrum, including a group of neurodegenerative disorders characterized by the abnormal accumulation of iron within the basal ganglia of the brain. Adversely, NBIA manifests symptoms such as progressive Parkinson's disease, spasticity, dystonia, retinal degeneration, optic atrophy, and a plethora of mental abnormalities. Its prevalence is low, occurring in an estimated 1 to 3 cases per million.
Overview of NBIA
NBIA refers to inherited neurodegenerative abnormalities characterized by the excessive deposits of iron in the basal ganglia. NBIA provides progressive parkinsonism, spasticity and dystonia, retinal degeneration with optic atrophy, mental deficiency, and several other signs. It's a relatively rare disease with an incidence from 1 to three cases in a million.
Fig. 1 Scheme of the proteins associated with NBIA disorders and their cellular localization. (Levi, Sonia, and Valeria Tiranti, 2019)The progression of NBIA is linked to genetic mutations in certain genes that include those of iron metabolism, coenzyme A biosynthesis, phospholipid metabolism, ceramide metabolism, and lysosomal diseases as well as genes of unknown function. The mutations within these genes disrupt important cellular processes, dysregulate iron homeostasis, and cause excess iron deposition within the brain. Consequently, neuronal loss takes place and eventually leads to increased neurodegeneration. At this point, there are a number of known genetic changes which are responsible for different subtypes of NBIA, as indicated in the table below.
Table. 1 Types of NBIA. (Tonekaboni, et al., 2014)
| NBIA Subtype | Gene | Inheritance |
|---|---|---|
| Pantothenate Kinase-associated Neurodegeneration (PKAN) | PANK2 | AR |
| PLA2G6-associated Neurodegeneration (PLAN) | PLA2G6 | AR |
| Mitochondrial Membrane Protein-associated Neurodegeneration (MPAN) | C19orf12 | AR |
| Beta-propeller Protein-associated Neurodegeneration (BPAN) | WDR45 | XLD |
| Fatty Acid Hydroxylase-associated Neurodegeneration (FAHN) | FA2H | AR |
| Kufor-Rakeb Syndrome | ATP13A2 | AR |
| Neuroferritinopathy | FTL | AD |
| Aceruloplasminemia | FTL | AR |
| Woodhouse-Sakati Syndrome | DCAF17 | AR |
| Coasy Protein-associated Neurodegeneration (CoPAN) | COASY | AR |
Diagnostics Development of NBIA
Timely diagnosis of NBIA is the key to successfully managing the disease. For NBIA diagnostic evaluation, various imaging tests are used for the presence of focal areas of iron deposits in the brain.
DaT scans
Transcranial Doppler sonography (TCD)
PET scans
Magnetic resonance imaging (MRI)
Therapeutics Development of NBIA
Currently, there is no cure found for any NBIA disease. For now, researchers are concentrating on understanding the pathogenesis and possible causes of NBIA in an effort to devise an effective therapeutic.
Iron Metabolism Pathways
One of the main mechanisms that causes NBIA is iron deposition in the brain. Therefore, regulating iron metabolism is one of the key targets. There are preclinical studies showing the promise of Deferiprone, an iron chelator. These chelators can bind to and sequester excess iron and thus reduce the neurodegenerative consequences of iron deposits.
Iron Metabolism Pathways
Another important target for the development of NBIA therapies is the modification of specific gene mutations. An example is PKAN which is caused by PANK2 gene mutations. Like with other experimental approaches, it includes an attempt to fix the existing gene defect to make the cells functional to mitigate the disease advancement.
Our Services
Because of our in-depth involvement in the investigation of rare diseases, our company possesses a highly competent team with extensive experience. We leverage advanced technologies to facilitate the development of novel diagnostic tools for early diagnosis of NBIA. We conduct research to develop animal models, allowing us to study the pathogenesis and molecular targets of NBIA in detail to create more effective therapeutic agents.
Research Platforms of NBIA
Our Services
Animal Models of NBIA
| Genetically Engineered Models | ||
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| Our company is dedicated to the development of genetic engineering models for NBIA. Through the utilization of gene knockout, knock-in and transgenic technology, we are able to create precise and dependable animal models. These models accurately replicate key features of NBIA, enabling researchers to study disease mechanisms, investigate potential therapeutic targets, and evaluate novel therapeutic strategies. | ||
| Optional Models |
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| Optional Species | Mice, Fruit Flies, Others | |
Whatever the stage of the research you are working on, we have specific research services to cater to all your needs. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
- Hayflick, Susan J., Manju A. Kurian, and Penelope Hogarth. "Neurodegeneration with brain iron accumulation." Handbook of clinical neurology 147 (2018): 293-305.
- Levi, Sonia, and Valeria Tiranti. "Neurodegeneration with brain iron accumulation disorders: valuable models aimed at understanding the pathogenesis of iron deposition." Pharmaceuticals 12.1 (2019): 27.
- Tonekaboni, Seyed Hassan, and Mohsen Mollamohammadi. "Neurodegeneration with brain iron accumulation: an overview." Iranian journal of child neurology 8.4 (2014): 1.
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