The rarity and diverse presentations of familial hemophagocytic lymphohistiocytosis (FHL) makes its treatment especially difficult. In an effort to solve the challenges of FHL management, Protheragen has invested sophisticated technologies and skilled personnel dedicated to developing innovative therapies. With our holistic support services, you will optimize the entire chain from development of drug candidate to commercialization.
Familial hemophagocytic lymphohistiocytosis (FHL) is an uncommon, inheritable hyper-inflammatory disorder marked by the unchecked immune system triggered system wide inflammation, damage to organs, and poses a high risk for death without treatment. FHL is a primary type of hemophagocytic lymphohistiocytosis (HLH) and results from inherited aberrations in the functioning of cytotoxic lymphocytes leading to poor immuno-regulation and a perilous 'cytokine storm'.
Fig. 1 Immune activation in familial hemophagocytic lymphohistiocytosis (FHL). (Steen, Erica A., et al., 2023)
Familial hemophagocytic lymphohistiocytosis (FHL) is directly linked to genetic pathologies such as PRF1, UNC13D, STX11, and STXBP2, which disable the effective functioning of cytotoxic lymphocytes, hence NK and CD8+ T cells are unable to remove activated immune cells. This defect causes uncontrolled T cell and macrophage activation, resulting in a hemophagocytosis and a cytokine storm (IFN-γ, TNF-α, IL-6/18). The inflammatory state may lead to hepatosplenomegaly, pancytopenia, multi-organ failure, central nervous system involvement.
Fig. 2 Uncontrolled T cell and macrophage activation leads to a cytokine storm and causes multi-organ damage. (Steen, Erica A., et al., 2023)
At present, therapy for familial hemophagocytic lymphohistiocytosis (FHL) involves intense immunosuppression and the only available cure, hematopoietic stem cell transplantation (HSCT). The risks of treatment-related malignancies, HSCT comorbidities, and absent regimen macromolecule-guided therapy remain significant problems which demonstrate the critical need for new treatment options. Developments in gene therapy, immune modulation, and precision medicine seem to offer viable solutions to these issues.
| Therapy | Type | Targets | Mechanism of Action | Development Stage |
|---|---|---|---|---|
| Emapalumab | Monoclonal antibody | IFN-γ | Neutralizes IFN-γ to reduce cytokine storm | Approved |
| Ruxolitinib | JAK inhibitor | JAK1/JAK2 | Blocks JAK-STAT signaling to suppress inflammation | Phase II/III |
| Anti-Thymocyte Globulin (ATG) | Polyclonal antibody | T cells | Depletes hyperactive T cells | Approved |
| PRF1 Correction | Gene therapy | PRF1 gene | Restores perforin function in cytotoxic cells | 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.
Advanced diagnostic and therapeutic solutions for familial hemophagocytic lymphohistiocytosis (FHL) are provided by Protheragen. With regard to FHL, we carefully target specific biomarkers for the disorder which allow us to create in vitro diagnostic (IVD) kits. Our therapeutic development services focus on crafting inovative therapies that target the primary causes of FHL. These therapies are comprehensively optimized and validated in disease models to ensure they effectively and precisely target the challenges posed by this complex disorder.
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| Induced Disease Models |
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At Protheragen, we foster the advancement of new therapies through holistic preclinical research services. This includes pharmacodynamics (PD), pharmacokinetic (PK) and toxicology studies, thereby covering all facets of evaluation of your therapeutic candidates. For further information regarding the scope of our services or quotations, do not hesitate to reach out.
Reference
Myeloproliferative Disorders (MPDs)
Bone Marrow Failure Syndromes (BMFS)