Telomere biology disorders (TBDs) stem from a malfunction in maintaining and functioning telomeres. At Protheragen, we are committed to solving TBDs by creating innovative therapeutics and designing precise animal models to expedite preclinical studies. Our expertise guarantees that your research is supported by the best service, accelerating your drug development process.
Telomere biology disorders (TBDs), also referred to as short telomere syndromes, are a set of infrequent heritable disorders due to defective telomere maintenance. Telomeres are the protective caps that are located at the ends of chromosomes and shorten with every cell division. In TBDs, there is excessive telomere shortening leading to excessive cell aging, bone marrow failure, and multi-organ failure.
Fig.1 The effects of long and short telomeres. (Roka, Kleoniki, et al., 2023)
Dysfunctions in telomere maintenance genes DKC1, TERT, TERC, or shelterin complex genes lead to critically shortened telomeres, cell senescence, and stem cell exhaustion which is characteristic of Telomere biology disorders (TBDs). Stem cell failure is enabled specifically within the rapidly proliferating tissues like bone marrow, immune system, and epithelial cells. Moreover, dysfunctional telomere associated DNA damage response (DDR) can further promote genomic instability and elevate predisposition to cancer.
Fig.2 Telomere and telomerase complex components and their associated diseases. (Kam, Michelle LW, et al., 2021)
The development of effective therapies is further complicated by the heterogeneity of telomere biology disorders (TBDs), lack of robust biomarkers for monitoring, and the need for interventions that can simultaneously protect multiple organ systems from progressive telomere attrition. These challenges underscore the urgent need for targeted approaches that can safely restore telomere maintenance or mitigate its downstream consequences.
| Therapy | Types | Targets | Mechanism of Action | Development Stage |
|---|---|---|---|---|
| Nucleoside Therapy | Nucleoside Supplementation | Telomerase | Enhances telomerase-mediated telomere elongation | Phase I |
| Danazol | Synthetic androgen | Androgen receptor | Upregulates TERT expression, slowing telomere attrition | Phase I/II |
| GRN510 | Gene therapy | TERT or TERC genes | Lentiviral delivery of functional telomerase components | Preclinical |
| Elamipretide | Peptide | Mitochondria (cardiolipin) | Reduces oxidative stress, may protect telomeres | Phase II |
| Oligonucleotides | RNA therapy | TERC stabilization | Replenishes defective TERC in DKC1 mutations | Discovery phase |
| PAPD5 Inhibitors | Small molecule | PAPD5 | Blocks TERC degradation in DKC1-mutant cells | Discovery phase |
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.
Protheragen, as a foremost provider of research services, is focused on developing diagnostic and therapeutic solutions for telomere biology disorders (TBDs). We offer extensive therapeutic development services, inclusive of but not limited to, gene therapy, small molecule pharmaceuticals, and therapeutic peptides. All these new strategies undergo strict validation and optimization in sophisticated disease models to ensure rapid translation of scientific innovations into commercial reality.
At Protheragen, we are committed to validating and optimizing therapies for telomere biology disorders (TBDs) through preclinical studies including pharmacodynamics (PD), pharmacokinetics (PK) and toxicology to ensure their successful regulatory approval. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
Myeloproliferative Disorders (MPDs)
Bone Marrow Failure Syndromes (BMFS)
