Alpha-Mannosidosis
Alpha-mannosidosis is a rare genetic disorder characterized by the deficiency or malfunction of an enzyme known as alpha-mannosidase. This enzyme plays a key role in breaking down complex sugar molecules called oligosaccharides. Our company is a leader in the field of rare diseases, with a particular focus on conditions such as alpha-mannosidosis, and offers a range of services to researchers in this field.
Overview of Alpha-Mannosidosis
Alpha-mannosidosis is an autosomal recessive disorder with an approximate incidence of 1 in 1,000,000 individuals. The deficiency of alpha-mannosidase leads to the accumulating of these sugar molecules within cells, resulting in various symptoms and complications. Individuals affected by alpha-mannosidosis may experience a variety of symptoms, including skeletal.
Fig.1 Brain MRI abnormalities in alpha-mannosidosis. (Majovska, J., et al., 2021)
Pathogenesis of Alpha-Mannosidosis
The genetic basis of this disorder lies in mutations within the MAN2B1 gene, which encodes for the lysosomal alpha-mannosidase enzyme. The pathophysiological mechanism of alpha-mannosidosis involves the impairment of lysosomal function due to the mutated MAN2B1 gene. Lysosomes are cellular organelles responsible for waste disposal within the cell. When the breakdown of oligosaccharides is disrupted, these sugar molecules accumulate within the lysosomes, leading to cellular dysfunction and subsequent damage to tissues and organs throughout the body.
Diagnostics Development of Alpha-Mannosidosis
Biochemical Testing
Biochemical testing to assess the activity of alpha-mannosidase enzyme in blood or other tissues. A confirmed diagnosis is made when there is low or absent enzyme activity detected.
Genetic Analysis
Genetic analysis can assist in identifying specific mutations in the MAN2B1 gene, which encodes alpha-mannosidase, confirming the genetic cause of the disorder.
Therapeutics Development of Alpha-Mannosidosis
| Therapies | Names/Types | Mechanism of Action | Targets | Research Phase |
|---|---|---|---|---|
| Enzyme replacement therapy | Velmanase alfa | Reduce the accumulation of oligosaccharides | alpha-mannosidase | Approved |
| rhLAMAN | Reduce the accumulation of oligosaccharides | alpha-mannosidase | Phase III trials | |
| Hematopoietic stem cell transplantation (HSCT) | Bone marrow transplantation | Correcting abnormal enzyme activity | / | Clinical trials |
| Gene therapy | Genome editing | Edit the defective gene | MAN2B1 | Preclinical research |
| AAV vector | Deliver the functional copy of the MAN2B1 gene | MAN2B1 | Preclinical research |
Our Services
Our company is committed to staying at the forefront of technological advancements relevant to rare diseases, allowing us to conduct advanced molecular and genetic analyses, biomarker identification, and drug discovery research. Relying on our animal models and therapeutic development platform, we are dedicated to advancing the understanding and therapy of these conditions.
Therapy Development Platforms
Animal Models of Alpha-Mannosidosis
Animal models play a crucial role in understanding the pathogenesis of genetic disorders like alpha-mannosidosis and in the development and evaluation of potential therapies. Our company offers a variety of animal models to help you understand the natural history of alpha-mannosidosis, elucidate the underlying mechanisms, and evaluate various therapy approaches.
Chemical-induced Models
Chemical-induced animal models of alpha-mannosidosis are created by administering specific chemicals that interfere with the normal function of the alpha-mannosidase enzyme or disrupt the metabolism of glycoproteins.
Optional Models: Ipomoea carnea-induced model, etc.
Genetically Engineered Models
Genetic engineering techniques such as CRISPR/Cas9 have been used to introduce mutations in the animal MAN2B1 gene, resulting in impaired alpha-mannosidase function, leading to the accumulation of oligosaccharides.
Optional Models: Man2b1tm1Psa model; Man2b1em9Gpt model, etc.
Why Choose Us
Our company has a highly skilled and experienced team of experts with deep knowledge and expertise in rare diseases. We offer comprehensive services including pharmacokinetic studies and drug safety evaluation, and are committed to supporting researchers to improve the understanding, diagnosis, and therapy of rare diseases.
If you are interested in learning more about our services and how we can support your research endeavors, please do not hesitate to reach out to us for further information.
References
- Park, Jong Eun et al. "Carrier frequency and incidence of alpha-mannosidosis: population database-based study-focus on the East Asian and Korean population." Frontiers in genetics 14 (2023): 1297543.
- Cholich, Luciana A et al. "Alpha-mannosidosis caused by toxic plants in ruminants of Argentina." Anais da Academia Brasileira de Ciencias 3 (2021): e20191496.
- Majovska, Jitka et al. "White matter alteration and cerebellar atrophy are hallmarks of brain MRI in alpha-mannosidosis." Molecular genetics and metabolism 132.3 (2021): 189-197.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.