The rarity of hemophagocytic lymphohistiocytosis (HLH), its tendency to progress rapidly, and the intricate control of the hyper-inflammatory response escalate the challenges associated with its treatment. These challenges related to the management of HLH are of primary concern to Protheragen. We are proud to be your trustworthy partner in HLH therapeutic research, where we offer all encompassing, high-caliber services tailored to meet all your research needs.
Overview of Hemophagocytic Lymphohistiocytosis (HLH)
Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening hyperinflammatory syndrome which involve uncontrollable immune activation, cytokine storm, and multi-organ dysfunction. It manifests in two main forms: primary HLH is genetic, stemming from gene mutations that affect cytotoxic lymphocyte function; secondary HLH is set off by infections, tumors, or autoimmune diseases. Familial HLH usually arises in infants or toddlers while secondary HLH can develop at any point in life.
Fig.1 Genetic factors that cause hemophagocytic lymphohistiocytosis (HLH). (Canna, Scott W., and Rebecca A. Marsh., 2020)
Pathogenesis of Hemophagocytic Lymphohistiocytosis (HLH)
In hemophagocytic lymphohistiocytosis (HLH), the main defect is insufficient cytotoxic activity of NK cells and CD8+ T lymphocytes, which leads to incomplete destruction of infected or neoplastic cells. This is characterized by persistent immune provocation, excessive cytokine release (e.g. IFN-γ, IL-6, TNF-α), and unchecked macrophage activation.
- Genetic Mechanisms: PRF1, UNC13D, STX11, STXBP2, LYST, etc.
- Infections: Epstein-Barr virus (EBV), cytomegalovirus (CMV), and Leishmania.
- Autoimmune Disorders: Individuals who have systemic lupus erythematosus, rheumatoid arthritis, or inflammatory bowel disease may experience HLH as a complication of their autoimmune disorder.
Therapy Development for Hemophagocytic Lymphohistiocytosis (HLH)
| Drug Names |
Mechanism of Action |
Targets |
NCT Number |
Research Phase |
| Ruxolitinib |
Suppresses hyperinflammation by blocking IFN-γ/IL-6 signaling. |
JAK1/JAK2 |
NCT04551131 |
Phase II/III |
| Venetoclax + Dexamethasone |
Induces apoptosis in hyperactivated lymphocytes and suppresses immune response. |
BCL-2/Glucocorticoid receptor |
NCT05546060 |
Phase I/II |
| Pegylated Liposomal Doxorubicin |
Intercalates DNA, inhibits topoisomerase II. |
DNA/Topoisomerase II |
NCT04077905 |
Clinical trials |
| Etoposide |
Induces DNA damage in proliferating immune cells. |
Topoisomerase II/DNA |
NCT01547143 |
Phase II |
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.
Our Services
Protheragen, as a specialized research service provider, focuses deeply on the rare lymphoproliferative disorders (LPDs) with emphasis on hemophagocytic lymphohistiocytosis (HLH). Our comprehensive services include the development of diagnostics and novel therapeutics, precision modeling of diseases, and thorough preclinical validation. We integrate research innovation with technology through HLH-specific model strategies to empower our partners at idea commercialization.
Animal Model Development Services
Animal models with mutations affecting lymphocytic toxicity and viral infection can accurately mimic the disease features of human HLH.
- Perforin-1 Knockout Model of Lymphocytic Choriomeningitis (LCMV) Infection
- Perforin-1 Knockout Model of Cytomegalovirus (CMV) Infection
Protheragen is steadfastly dedicated to meticulously validating and optimizing therapies for hemophagocytic lymphohistiocytosis (HLH) through a thorough series of pharmacodynamics (PD), pharmacokinetics (PK) and toxicology studies. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
Reference
- Canna, Scott W., and Rebecca A. Marsh. "Pediatric hemophagocytic lymphohistiocytosis." Blood, The Journal of the American Society of Hematology 135.16 (2020): 1332-1343.
