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Dopamine Transporter Deficiency Syndrome (DTDS)

As of now, dopamine transporter deficiency syndrome (DTDS) has no existing cure, and treatment options are mostly palliative, concentrating on managing symptoms. Protheragen has assembled a skilled team of researchers and scientists with diverse experience in DTDS. They are relentless in efforts towards innovation in the treatment of DTDS by developing and optimizing novel therapies that seek to address the gaps in treatment and deepen therapeutic innovation within the disease.

Overview of Dopamine Transporter Deficiency Syndrome (DTDS)

Dopamine transporter deficiency syndrome (DTDS) is a rare condition and an autosomal recessive inheritance disorder which is a lot more difficult to diagnose. It is characterized by severe infantile parkinsonism-dystonia, developmental delays, and a progressive decline in neurological function. In 2009, DTDS was identified as a result of loss-of-function mutations in the SLC6A3 gene and its DAT (dopamine transporter) protein product. DAT is essential in the reuptake of synaptic dopamine. Its ineffectiveness leads to unregulated dopaminergic signaling, particularly in the case of the nigrostriatal pathway.

Fig.1 Schematic of dopamine transporter deficiency syndrome (DTDS) current therapies, patient diagnosis, and novel therapeutics. (Ng J, et al., 2023)

Pathogenesis of Dopamine Transporter Deficiency Syndrome (DTDS)

Biallelic changes in the SLC6A3 gene, which codes for the dopamine transporter, lead to dopamine transporter deficiency syndrome (DTDS) because the encoded transporter is unable to facilitate dopamine's synaptic reuptake leading to neurotransmission dysregulation. Without the dopamine transporter (DAT), there is too much dopamine outside the cells, leading to receptor desensitization, and oxidative stress. This results in the dysfunction of the basal ganglia and manifests as severe parkinsonism-dystonia plus progressive neurological deterioration that begins in infancy.

Dopaminergic synaptic regulation through metabolic control and membrane trafficking of dopamine transporters. Fig.2 Regulation of dopamine metabolism and dopamine transporter surface expression in the synaptic cleft. (Shaikh A, et al., 2023)

Therapeutic Development for Dopamine Transporter Deficiency Syndrome (DTDS)

Drug Names	Mechanism of Action	Targets	Research Phase
Tetrabenazine	Vesicular monoamine transporter 2 (VMAT2) inhibitor; depletes presynaptic dopamine stores by blocking synaptic vesicle uptake.	VMAT2 (SLC18A2)	Early research
Benzodiazepines	Positive allosteric modulators of GABAA receptors; enhance inhibitory neurotransmission to mitigate dystonia/hyperkinesia.	GABAA receptor subunits	Approved
Pramipexole	Dopamine D2/D3 receptor agonist; bypasses DAT dysfunction to directly stimulate postsynaptic receptors.	Dopamine D2/D3 receptors (DRD2/DRD3)	Preclinical

Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.

Our Services

As a professional provider of preclinical research services, Protheragen focuses on accelerating developments in the area of dopamine transporter deficiency syndrome (DTDS). Our services range from comprehensive diagnostic development, novel therapeutic development, accurate disease modeling, to comprehensive preclinical validation. Through our blood-brain barrier model, we assess drug permeability in the central nervous system (CNS), ensuring maximal delivery to the brain and minimal exposure to the body to reduce toxicity, which facilitates the development of effective therapies.

Therapeutic Development Services

By Molecule Types

By Mechanism of Action

Disease Model Development Services

Model Types	Model Names
In Vitro Models	Patient-Derived Cell Model Neuronal Cell Model Glial Cell Model	Co-Culture Model Brain Organoid Spinal Cord Organoid
Microfluidic Models	Neurovascular Unit Model Axon Degeneration Model Neuroinflammation Model	Neuromuscular Junction Model Synaptic Plasticity Model Organoid-on-a-Chip Model
Animal Models	DAT-KO Mouse Model: A complete knockout of the dopamine transporter (DAT) gene, exhibiting hyperdopaminergic activity with elevated extracellular dopamine levels, severe hyperactivity, and motor deficits, mimicking core features of human DTDS. A313V Knock-in DAT Variant Model: A point mutation in the DAT gene (analogous to human pathogenic variants) that impairs dopamine reuptake while preserving partial transporter expression, providing a more clinically relevant model of DTDS with graded dopaminergic dysfunction.

At Protheragen, we offer comprehensive pharmacodynamic (PD), pharmacokinetic (PK), and toxicology research services to support the development and regulatory approval of potential therapies for dopamine transporter deficiency syndrome (DTDS). If you are interested in our services, please feel free to contact us for more details and quotation information of related services.

References

Ng J, Barral S, Waddington S N, et al. Dopamine transporter deficiency syndrome (DTDS): expanding the clinical phenotype and precision medicine approaches[J]. Cells, 2023, 12(13): 1737.
Shaikh A, Ahmad F, Teoh S L, et al. Targeting dopamine transporter to ameliorate cognitive deficits in Alzheimer's disease[J]. Frontiers in Cellular Neuroscience, 2023, 17: 1292858.

For research use only. Not intended for any clinical use.