Aromatic L-Amino Acid Decarboxylase Deficiency (AADCD)
Aromatic L-amino acid decarboxylase deficiency (AADCD) is a rare genetic disease caused by mutations in the DDC gene. With our company's profound expertise in AADCD research, we are well-equipped to offer tailored solutions and comprehensive support to facilitate your research process from AADCD therapy development to therapy commercialization.
Overview of AADCD
AADCD is a rare genetic disorder that affects the synthesis of dopamine and serotonin (neurotransmitters). Individuals affected by AADCD often experience symptoms such as hypotonia, ophthalmological crises, and developmental delays. In the United States, the estimated prevalence is approximately 1-3/100,000 live births based on cerebrospinal fluid (CSF) analysis and genetic testing.
Fig. 1 Phenylalanine and tryptophan metabolism pathways are altered due to AADCD. (Pappan, et al., 2017)AADCD is an autosomal recessive disorder characterized by mutations in the DDC gene, leading to decreased or absent activity of the AADC enzyme. Consequently, the transformation of aromatic L-amino acids, such as L-dopa and 5-hydroxytryptophan, into dopamine and serotonin is profoundly impaired. This disruption in neurotransmitter synthesis interferes with the proper functioning of neuronal signaling pathways, giving rise to a range of symptoms in individuals affected by AADCD.
Diagnostics Development of AADCD
In recent years, there have been ongoing advancements in the diagnostic approaches for AADCD, predominantly employing a combination of symptom evaluation, biochemical assays, and genetic testing.
Symptom Evaluation
This approach guides the subsequent diagnostic investigations by assessing the symptoms, disease history, and family history of individuals with AADCD. A comprehensive assessment aids in the initial diagnosis of the condition.
Biochemical Assays
Lumbar puncture is often used to analyze neurotransmitter levels in the cerebrospinal fluid, revealing characteristic abnormalities associated with AADCD. In addition, AADC enzyme activity testing can be used to further confirm the diagnosis.
Genetic Testing
Genetic testing utilizes advanced molecular techniques, like DNA sequencing, to analyze both coding and noncoding regions of the DDC gene. By identifying specific mutations, it enables accurate diagnosis of AADCD and supports tailored therapeutics.
Therapeutics Development of AADCD
- Therapeutic Drugs of AADCD
Pharmacological therapies for AADCD primarily involve the use of medications that target the dopaminergic and serotonergic pathways to supplement the deficient neurotransmitter levels.
Dopamine Agonists
Dopamine agonists stimulate dopamine receptors in the brain, mimicking the action of dopamine. These medications help alleviate symptoms such as movement disorders, muscle stiffness, and motor fluctuations. Examples of dopamine agonists used in AADCD therapeutics include levodopa/carbidopa, pramipexole, and ropinirole.
Monoamine Oxidase Inhibitors (MAOIs)
MAOIs work by inhibiting the activity of monoamine oxidase enzymes, which are responsible for the breakdown of dopamine and serotonin. By blocking this enzymatic degradation, MAOIs increase the availability of these neurotransmitters in the brain. Selegiline and rasagiline are examples of MAOIs used in the therapeutics of AADCD.
- AADCD Gene Therapy
Gene therapy strategies aim to restore the normal function of the AADC enzyme, enabling proper synthesis of dopamine and serotonin. Approaches such as gene replacement therapy and gene editing technologies are anticipated to restore gene function and enhance AADC enzyme production.
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 AADCD.
- AADCD Diagnostic Development Services: For rare genetic diseases such as AADCD, our company offers diagnostic development services and state-of-the-art next-generation sequencing (NGS) products. We are dedicated to assisting you in the development of rapid and point-of-care diagnostic tests for AADCD, ensuring accurate and timely detection.
- AADCD 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 possess significant expertise in utilizing viral vectors for gene therapy and employing CRISPR-Cas9 gene editing techniques.
- AADCD Animal Model Development Service: To support the preclinical research and development of AADCD therapeutics, we offer AADCD animal models development services, including the Ddc knockout mouse model and IVS6+4A>T knock-in mouse model to facilitate your pharmacokinetics study and drug safety evaluation.
| Genetically Engineered Models | ||
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| Our company excels in the development of genetically engineered models for AADCD research. Leveraging our expertise in genetic engineering techniques, particularly CRISPR/Cas9 technology, we create highly precise and reliable models that faithfully reproduce the genetic alterations observed in individuals with AADCD. | ||
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| Optional Species | Mice, Zebrafish, Non-human Primates, Fruit Flies, Caenorhabditis Elegans, 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 of related services.
References
- Pappan, Kirk L., et al. "Clinical metabolomics to segregate aromatic amino acid decarboxylase deficiency from drug-induced metabolite elevations." Pediatric Neurology 75 (2017): 66-72.
- Himmelreich, Nastassja, et al. "Aromatic amino acid decarboxylase deficiency: molecular and metabolic basis and therapeutic outlook." Molecular genetics and metabolism 127.1 (2019): 12-22.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.