Alpha-Thalassemia (A-THAL)
Alpha-thalassemia is a form of thalassemia. With our company's profound expertise in A-THAL research, we are well-equipped to offer tailored solutions and comprehensive support to facilitate your research process from A-THAL therapy development to therapy commercialization.
Introduction to A-THAL
A-THAL is a rare genetic disorder characterized by reduced or absent production of alpha-globin chains, resulting in abnormal hemoglobin formation. There is a dearth of public health data regarding A-THAL in the United States. However, in California, the prevalence of A-THAL is observed to be 1 in 10,000 births. There are two main forms of A-THAL associated with serious health problems: hemoglobin (Hb) Bart's hydrops fetalis and hemoglobin H (HbH) disease.
| Disease Types | Phenotype | Onset Time |
|---|---|---|
| Hemoglobin (Hb) Bart's Hydrops Fetalis | Mild or Moderate Anemia | Onset in Childhood or Adulthood |
| Hemoglobin H (HbH) Disease | Severe Anemia | Onset during the Fetal Period |
Pathogenesis of A-THAL
The pathogenesis of A-THAL is associated with impaired alpha-globin chain production, leading to imbalanced globin chain synthesis and abnormal hemoglobin formation. This affects the normal structure and function of red blood cells, leading to their premature destruction and subsequent anemia. Potential genetic mutations that cause A-THAL involve deletions or point mutations in the HBA1 and HBA2 genes. These mutations result in reduced or absent α-globin chain synthesis.
Fig. 1 Schematic presentation of the chromosomal location of the α- and β-globin gene clusters on 16p and 11p respectively. (Farashi, Samaneh, and Cornelis L. Harteveld., 2018)Targets of A-THAL Therapy
Alpha-globin
Enhancing the synthesis of α-globin chains and promoting the formation of functional hemoglobin are important targets for the development of A-THAL therapies. For example, luspatercept may increase hemoglobin levels and reduce the need for transfusions in individuals affected by A-THAL.
Pyruvate Kinase-R (PKR)
Pyruvate kinase-R (PKR) is an enzyme that plays a key role in erythrocyte glycolysis. The drug under investigation, AG-348, can enhance the activity of pyruvate kinase-R (PKR), increase red blood cell energy production, and improve erythropoiesis.
A-THAL Gene Therapy
Using lentiviruses or adeno-associated viruses (AAV), functional copies of the HBA1 and HBA2 genes encoding alpha-globin chains are delivered into the hematopoietic stem cells of A-THAL individuals. Once integrated into the genome, these genes can drive the production of normal alpha globin chains, thereby restoring functional hemoglobin.
Our Services
Drawing upon our deep expertise in biotechnology and extensive experience in the industry, our company offers all-encompassing solutions for diagnostic and therapeutic research dedicated to A-THAL.
- A-THAL Diagnostic Development Services: For rare genetic diseases such as A-THAL, our company offers diagnostic development services. We are dedicated to assisting you in the development of rapid and point-of-care diagnostic tests for A-THAL, ensuring accurate and timely detection.
- A-THAL Therapeutic Development Services: Our company provides a wide range of services for the development of small molecule drug, cell therapy, gene therapy, therapeutic antibody, therapeutic peptide, and therapeutic protein. We are experienced in utilizing lentiviruses or adeno-associated viruses (AAV) vectors for gene therapy.
- A-THAL Animal Model Development Service: To support the preclinical research and development of A-THAL therapeutics, we offer A-THAL animal models development services to facilitate your pharmacokinetics study and drug safety evaluation.
| Genetically Engineered Models | ||
|---|---|---|
| Genetically engineered models are created by modifying the genetic makeup of experimental animals to simulate specific characteristics or mutations associated with human A-THAL. At our company, scientists specialize in using CRISPR/Cas9 and transgenic technologies to create knockout, knock-in, and transgenic models. | ||
| Optional Models |
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| Optional Species | Mice, Zebrafish, Non-human Primates (Rhesus Macaques), Others | |
No matter what stage of research you are at, we can provide you with corresponding research services. If you are interested in our services, please feel free to contact us for more details and quotation information for related services.
References
- Farashi, Samaneh, and Cornelis L. Harteveld. "Molecular basis of α-thalassemia." Blood Cells, Molecules, and Diseases 70 (2018): 43-53.
- Horvei, Paulina, Tippi MacKenzie, and Sandhya Kharbanda. "Advances in the management of α-thalassemia major: reasons to be optimistic." Hematology 2021.1 (2021): 592-599.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.