There are limited treatment options available for short telomere syndrome (STS) and existing therapies of hematopoietic stem cell transplantation (HSCT) are often complicated by poor engraftment and organ toxicity. Protheragen has taken the initiative to devise new strategies for the treatment of STS in order to manage the problems with STS effectively.
Short telomere syndrome (STS) is an uncommon genetic disease characterized by relatively short telomeres, which are the protective structures at the ends of chromosomes. STS leads to limited cellular reproduction, worsening bone marrow failure, pulmonary fibrosis, and liver cirrhosis which are exacerbated through chronic progression and usually show symptoms in young adulthood. The pathology of STS derives from the mutations in telomere maintenance genes which severely reduce telomerase activity, accelerating cell aging.
Fig. 1 Telomere, shelterin complex and telomerase complex. (Roka, Kleoniki, et al., 2023)
Short telomere syndrome (STS) arises from critically short telomeres due to canonical genetic defects from TERT, TERC, DKC1, RTEL1 or TINF2. These genes interfere with protective protein complex structure or suppress telomerase activity, resulting in a p53 mediated DNA damage response and subsequent premature senescenceof stem cells leading to exhaustion.
Fig. 2 Causes of telomere shortening and its biological consequences. (Ruiz, Andy, et al., 2021)
The main treatments for short telomere syndrome (STS) continue to be allogeneic hematopoietic stem cell transplantation (HSCT), with difficulties like high toxicity and limited donor pools still plagued. The lack of established disease-modifying therapies highlights the need for greater efforts focused on restoring telomere function or reducing the telomere-related damage. Many therapies in development are focused on addressing these problems.
| Therapy | Targets | Mechanism of Action | Development Stage |
|---|---|---|---|
| Danazol | Androgen receptor | Activates TERT transcription to elongate telomeres | Clinical |
| TERT/TERC Gene Therapy | TERT or TERC genes | Viral vector delivery to restore telomerase activity | Preclinical |
| PAPD5 Inhibitors | PAPD5 | Prevents telomerase RNA degradation | Discovery Phase |
| Hematopoietic Stem Cell Transplantation (HSCT) | Hematopoietic Stem Cells | Combines HSCT with telomerase-activating agents | Clinical |
| mTOR Inhibitors | mTOR pathway | Reduces cellular senescence and inflammation | 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.
To improve the management of short telomere syndrome (STS), Protheragen provides strategic services in diagnostic and therapeutic development, utilizing our great inventive capabilities and technologies. Comprehensively attending to the various molecular pathways responsible for STS, we strive to develop pioneering, innovative, and targeted therapeutic solutions. Our team spares no effort in devising precise disease models which allow the refined study of the possible therapeutics' safety, efficacy, and mode of action.
At Protheragen, we offer comprehensive pharmacodynamic (PD), pharmacokinetic (PK), and toxicology research services to support the development and regulatory approval of potential therapies for short telomere syndrome (STS). 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)
