Tuberous Sclerosis Complex (TSC) is an uncommon genetic condition which affects multiple systems and is distinguished by the development of non-cancerous tumors (hamartomas) in the brain, skin, heart, kidneys and lungs. Protheragen remains committed in providing preclinical drug and therapy development services to advance translational research aimed toward improving therapeutic solutions for TSC.
Introduction to Tuberous Sclerosis Complex
Like many other complex health issues in modern society, TSC stems from an ever-evolving fracture within genetics where one inherits mutations of TSC1 or TSC2 genes which presents itself as an autsomal dominant condition. The disorder has a broad range of symptoms both qualitatively and quantitatively attributes such as developmental disabilities and intellectual deficits alongside characteristic dermal lesions. Such complexity renders effective treatment mitigate from one's eyes throughout their life becasue the degree to which you suffer varies considerably.
Pathogenesis of Tuberous Sclerosis Complex
Hypomorphic mutations within TSC1 or TSC2 can result in tuberous sclerosis complex due to loss-of-function alterations that disrupt mTORC1 signaling via hamartin and tuberin. Unchecked mTORC1 activity causes excessive cell growth; fibrotic skin lesions form due to heightened metabolism coupled with cell growth and reprogramming. Further skin lesions are sustained through insufficient autophagy countered by super angiogenesis as well as systemic inflammation while more recent studies suggest mTOR hyperactivity as an underlying cause enhancer for dysfunction in melanocytes formation which leads to hypopigmented macules along with photosensitivity.
Fig.1 TSC-mTOR pathway. (Marom, 2020)
Therapeutics Development for Tuberous Sclerosis Complex
mTOR-Targeted Therapies
Next-generation mTOR inhibitors attempt to overcome resistance mechanisms by targeting distinct catalytic sites and show some promise in preclinical and early clinical studies. Some mid-stage clinical trials are exploring repurposed metabolic modulators that seek to synergistically inhibit downstream signaling pathways for TSC symptoms.
Non-mTOR Pathway Interventions
New concepts concentrating on the modulation of neuroinflammation and ion channels use cytokine-specific blockers and neuromodulatory agents currently in preclinical development. There is also study of compounds derived from cannabinoids with early clinical assessments demonstrating good tolerability for behavioral and seizure control.
Advanced Cell and Gene Therapies
Preclinically successful gene therapy approaches using viral vectors to replace genes have been able to restore functional protein expression, alleviating certain neurological deficits. There is progress towards first-in-human trials for tumor-associated complications from more advanced translational studies on engineered cellular therapies using oncolytic vectors with immunomodulatory payloads.
Our Services
Protheragen incorporates multidisciplinary research such as dermatology, genetics, and molecular biology with focus on the tuberous sclerosis complex which includes mTOR pathway dysregulation and tumorigenesis aimed at therapeutic development and disease model development tailored to your research objectives.
Therapeutic Development Platforms for Tuberous Sclerosis Complex
Through small molecule modulators aimed at normalizing mTOR signaling, autophagy in TSC1/TSC2 deficient cells, gene editing aimed at restoring protein function expression, and biologics like cytokine neutralizing antibodies to mitigate inflammation driven tumor and fibrotic growth, Protheragen is actively developing therapies focused on the TSC disease process.
Disease Model Development for Tuberous Sclerosis Complex
Protheragen offers a comprehensive preclinical portfolio for TSC, including 2D cell models, 3D skin models and animal models engineered to replicate hallmark pathologies such as cutaneous hamartomas and neuronal dysregulation, enabling robust therapy evaluation.
| 2D Cell Models & 3D Skin Models |
| Protheragen utilizes 2D cell models and advanced 3D skin models to dissect mTOR pathway dynamics and assess drug candidates for skin-specific manifestations of TSC. |
| Optional Models |
- TSC1/TSC2-Knockout Human Keratinocytes
- Patient-Derived iPSC Models with Cortical Tuber Phenotypes
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- 3D Tumoroid Co-Cultures (Neuronal + Epidermal Cells)
- Vascularized Skin-on-a-Chip Systems for Angiofibroma Studies
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| Animal models |
| Protheragen's preclinical in vivo studies employ animal models, including genetically engineering models tailored to tuberous sclerosis complex, to evaluate therapeutic safety and efficacy while ensuring biological relevance to disease mechanisms. |
| Optional Models |
- Global Tsc1/Tsc2 Knockout Mice
- KRT14 Conditional Knockout Mice
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- tsc2 Mutants Zebrafish Models
- Conditional Tsc1 Knockout Rats
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| Optional Species |
Mice, Rats, Non-human primates, Others |
As a specialized preclinical research partner, Protheragen supports therapeutic innovation for rare skin disorders like tuberous sclerosis complex. Our end-to-end services include target discovery, disease modeling, drug safety evaluation and DMPK services. If you are interested in our services, please feel free to contact us.
References
- Curatolo, P., N. Specchio, and E. Aronica. "Advances in the Genetics and Neuropathology of Tuberous Sclerosis Complex: Edging Closer to Targeted Therapy." Lancet Neurol 21.9 (2022): 843-56.
- Marom, D. "Genetics of Tuberous Sclerosis Complex: An Update." Childs Nerv Syst 36.10 (2020): 2489-96.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
