Homozygous Familial Hypercholesterolemia (HoFH)
Homozygous familial hypercholesterolemia (HoFH) is a rare but serious genetic disorder that results in extraordinarily high levels of low-density lipoprotein cholesterol (LDL-C) in the bloodstream. Our company specializes in providing a robust suite of comprehensive, one-stop services tailored for researchers and scientists dedicated to the study of rare diseases, including HoFH.
Overview of HoFH
HoFH characterized by its autosomal dominant inheritance pattern, leads to early onset atherosclerotic disease due to key defects in the LDL receptor (LDLR) pathway. The prevalence of HoFH ranges from 1 in 300,000 to 1 in 360,000 individuals. It is notably more severe than its counterpart, heterozygous familial hypercholesterolemia (HeFH), and carries a significantly elevated risk of premature cardiovascular disease.
Fig.1 Step-by-step HoFH therapy algorithm. (Kayikcioglu, M., and Tokgozoglu, L., 2022) Pathogenesis of HoFH
At the root of HoFH lies a primarily mutation-driven disruption of the LDLR gene, but also potentially influenced by defects in genes like APOB and PCSK9. LDLR gene is crucial for managing the removal of LDL-C from the bloodstream, and its mutation leads to a drastic reduction or complete absence of LDL receptor activity. Consequently, the impaired clearance of LDL-C results in its excessive build-up, which manifests as cholesterol-laden deposits across various tissues. These deposits accumulate within arterial walls, contributing to the formation of atherosclerotic plaques.
Fig.2 Lipid lowering agents used for HoFH therapy and their mode of action. (Kayikcioglu, M., and Tokgozoglu, L., 2022)Diagnostics Development of HoFH
Genetic testing plays a crucial role in confirming the diagnosis of HoFH. It helps identify mutations in genes associated with LDL-C metabolism, such as LDLR, APOB, and PCSK9. Identifying specific mutations aids in determining the prognosis, guiding therapy decisions, and assessing the risk of cardiovascular complications.
Therapeutics Development of HoFH
| Agents | Types | Mechanism of Action | Targets | Research Phase |
|---|---|---|---|---|
| Alirocumab | Monoclonal antibody | Inhibits PCSK9 | PCSK9 | Approved |
| Evinacumab | Monoclonal antibody | Monoclonal antibody to ANGPTL3 | ANGPTL3 | Approved |
| Ezetimibe | Small molecule drug | Inhibits NPCILI protein | NPCILI | Approved |
| Lomitapide | Small molecule drug | Inhibits MTP, thereby interfering with the assembly of lipoproteins | MTP | Approved |
| Mipomersen | Small molecule drug | A second-generation antisense oligonucleotide (ASO) inhibitor targeting ApoB | ApoB | Approved |
| Inclisirian | Small interfering ribonucleic acid | SiRNA inhibiting the translation of PCSK9 | PCSK9 | Approved |
| ARO-ANG3 | Small interfering ribonucleic acid | A siRNA targeting the ANGPTL3 gene | ANGPTL3 | Phase II trials |
| Lerodalcibep | Recombinant fusion protein | Suppress PCSK9 and LDL-C | PCSK9 / LDL-C | Phase III trials |
Our Services
Our company has comprehensive one-stop services, a collaborative network, and expertise in rare diseases, with our animal models and therapeutic development platform, we are committed to advancing research and ensuring researchers have the necessary support at every stage of their project.
Therapy Development Platforms
Animal Models of HoFH
Animal models provide valuable insights into certain aspects of HoFH and remain crucial for understanding HoFH and developing effective therapeutics. Our company provides a variety of animal models for you to study disease progression and evaluate therapeutic interventions.
HoFH-like phenotypes have been induced in animals through gene editing techniques, such as CRISPR/Cas9, targeting LDLR or other genes involved in cholesterol metabolism.
Optional Models: Ldlrtm1Her model; Apobtm2Sgy model; Pcsk9tm1Jdh model, etc.
Why Choose US
We are dedicated to supporting researchers and scientists in their pursuit of scientific excellence and improving the lives of individuals affected by HoFH.
If you want to learn more about our services and how we can support your research endeavors, please do not hesitate to contact us for further information.
References
- Kayikcioglu, Meral, and Lale Tokgozoglu. "Current Treatment Options in Homozygous Familial Hypercholesterolemia." Pharmaceuticals (Basel, Switzerland) 16.1 (2022): 64.
- Nohara, Atsushi et al. "Homozygous Familial Hypercholesterolemia." Journal of atherosclerosis and thrombosis 28.7 (2021): 665-678.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.