Hutchinson-Gilford Progeria Syndrome (HGPS)
Hutchinson-Gilford progeria syndrome (HGPS) is an incredibly rare genetic disorder that fast-forwards the aging process, beginning in early childhood. At our company, we have dedicated ourselves to the paramount endeavor of diagnosing and treating rare diseases and designing innovative research programs to develop potential therapies.
Overview of HGPS
HGPS, a genetic disorder, affects only 1 in 4 to 8 million live births. Beyond the limitations of its occurrence, the disease characteristically accelerates aging during a child's first years of life. Its symptoms include growth failure, loss of body fat and hair, aging skin, stiffness of joints, hip dislocation, generalized atherosclerosis, cardiovascular disease, and stroke.
Fig.1 Hallmarks of HGPS. (Cisneros, B., et al., 2023)Pathogenesis of HGPS
The pathogenesis of HGPS is the mutations in the LMNA gene coding for lamin A and lamin C, proteins integral to the nuclear envelope's structure. The most common mutation is a single-base substitution at coding position 608 of the LMNA gene, which creates a mutant protein named progerin. Progerin lacks a processing site necessary for lamin A's final maturation, consequently provoking structural changes in the nuclear envelope. This gathered progerin interrupts cell processes such as DNA repair, transcription, and cell proliferation, driving the premature aging cellular phenomenon symptomatic of progeria.
Fig.2 The beneficial effects of different therapies on the HGPS cellular phenotype. (Guilbert, S. M., et al., 2021)Diagnostics Development of HGPS
Typical diagnosis around a mesh of medical history, physical examination, and precise diagnostic tests. Genetic testing has proven the most definitive, in detecting LMNA gene mutation. Moreover, therapeutic efficiency can be evaluated using key markers during the research phase.
Therapeutics of HGPS
Small Molecule Drugs Therapy
Drugs such as MG132, JH4, farnesyltransferase inhibitor (lonafarnib), remodelin, and the mTOR inhibitor (rapamycin) reduce progerin synthesis and toxicity, managing HGPS symptoms.
Gene Therapy
Gene therapy's design is to hinder progerin accumulation, such as CRISPR/Cas9-mediated reduction of lamin A/progerin, thereby improving HGPS mice's health and lifespan.
Our Services
In an endeavor to spur progress in rare disease research, our company pairs innovation with advanced technology and professional expertise. We augment your research work on HGPS with services backed by our animal models and therapeutic development platform.
Therapy Development Platforms
Animal Models of HGPS
Various animal models have been used for understanding HGPS and finding potential therapeutic strategies. These models aim to mimic the genetic mutations and phenotypic characteristics observed in human individuals with HGPS. We offer a gamut of genetic engineering models to enrich your HGPS research.
| Genetically Engineered Models | ||
| Based on transgenic or gene editing techniques such as CRISPR/Cas9 to modify targeted genes, for example, LMNA, impacting the expression or activity of significant molecules to display the nuclear envelop abnormalities seen in HGPS. | ||
| Optional Models |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
||
| Optional Species | Mice, Rats, Non-Human Primates, Others | |
As a leader in rare disease research, we are poised to offer comprehensive services to support you at every research stage, incorporating pharmacokinetics studies and biosafety evaluation. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
- Cisneros, Bulmaro et al. "Hutchinson-Gilford Progeria Syndrome: Cellular Mechanisms and Therapeutic Perspectives." Archives of medical research 54.5 (2023): 102837.
- Batista, Noelle J et al. "The Molecular and Cellular Basis of Hutchinson-Gilford Progeria Syndrome and Potential Treatments." Genes 14.3 (2023): 602.
- Guilbert, Solenn M et al. "Hutchinson-Gilford progeria syndrome: Rejuvenating old drugs to fight accelerated ageing." Methods (San Diego, Calif.) 190 (2021): 3-12.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.