HTLV-1-Associated Myelopathy (HAM)
HTLV-1-Associated Myelopathy (HAM) is a slowly progressive, virus-immune-mediated spinal cord disease caused by Human T-lymphotropic Virus 1 (HTLV-1). Specialized drug and therapy development services are essential to enhance and expedite HAM research. Our company is well-equipped to address your drug and therapy development requirements in HAM therapy.
Introduction to HTLV-1-Associated Myelopathy
HTLV-1-associated myelopathy is a chronic neurological condition linked to Human T-lymphotropic virus type 1 infection. While the global prevalence of HTLV-1 infection ranges widely, the development of HAM occurs in only about 0.25% to 3% of infected individuals. The disease's progression is typically slow, and it involves a complex interaction of viral and host genetic factors influencing the immune response and disease severity.
Fig. 1 HTLV‑1 life cycle. (Bangham, C.R., et al., 2015)Pathogenesis of HTLV-1-Associated Myelopathy
The pathogenesis of HAM involves a complex interplay between viral factors and the host immune response. Initially, the HTLV-1 virus infects T-lymphocytes, leading to chronic activation and clonal expansion of these cells. The viral proteins Tax and HBZ play crucial roles in promoting viral replication and persistence within the host. The progression is characterized by inflammatory infiltrates in the central nervous system. This inflammatory response is largely mediated by HTLV-1-infected cells and the immune system's response, which fails to completely eliminate the virus but instead contributes to tissue damage through chronic inflammation and immune activation.
Fig. 2 Proposed mechanism of tissue damage in HAM. (Bangham, C.R., et al., 2015)Diagnosis Development of HTLV-1-Associated Myelopathy
The development of diagnostic methods for HTLV-1-associated myelopathy primarily focuses on identifying specific biomarkers. These biomarkers include HTLV-1 proviral load (PVL), measured in both peripheral blood mononuclear cells (PBMCs) and cerebrospinal fluid (CSF), which correlates closely with disease progression. Other crucial biomarkers involve inflammatory cytokines and chemokines such as IFN-γ, TNF-α, CXCL10, and CXCL9, which are significantly elevated in the blood and CSF of HAM/TSP individuals and can predict disease progression and severity.
Therapy Development of HTLV-1-Associated Myelopathy
For instance, drugs that inhibit NF-κB, a key factor in the inflammatory response associated with HAM/TSP, are being studied. Additionally, molecules targeting protease inhibitors and reverse transcriptase inhibitors, similar to those used in HIV therapy, are being tested due to the retroviral nature of HTLV-1.
This approach aims to reduce the viral load and mitigate the immune response that contributes to neurological damage. Another promising area is the use of mesenchymal stem cells (MSCs) to modulate the immune system and potentially repair neural damage through their regenerative capabilities.
Monoclonal antibodies targeting immune modulators such as cytokines involved in inflammation (e.g., TNF-α, IL-6) are being explored. These antibodies are designed to neutralize the inflammatory signals thereby reducing the spinal cord damage seen in HAM/TSP individuals.
Gene therapy approaches focus on silencing or modulating the expression of viral genes. Techniques include using antisense oligonucleotides or CRISPR/Cas9 systems to disrupt the viral genome or suppress the expression of specific viral proteins that play a role in the immune response.
Our Services
Our company adopts a partnership-driven approach. We collaborate closely with clients to craft tailored, innovative HAM therapy strategies and ensure robust support throughout the process.
Platforms of HTLV-1-Associated Myelopathy Therapy Development
Animal Models of HTLV-1-Associated Myelopathy
We have established expertise in developing and utilizing relevant animal models that closely mimic the disease characteristics and response to therapy. These models enable us to evaluate the safety and efficacy of potential therapies.
| Non-Genetically Engineering Models | ||
| We provide diverse model choices customized to meet specific research needs related to HAM. These models allow researchers to simulate and study the complex biological processes associated with HAM. | ||
| Biologics Induced Model | ||
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| Xenograft Model | ||
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| Genetically Engineered Models | ||
| Our expertise in genetic engineering techniques, such as CRISPR/Cas9 technology, allows us to generate accurate and reliable models that recapitulate the genetic alterations observed in human HAM. | ||
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| Optional Species | Mice, Rats, Non-human primates, Others | |
In addition to these models, our comprehensive services encompass other models that target specific signaling pathways and molecular targets.
If our services align with your goals, please contact us for more details.
References
- Bangham, C.R., et al., "HTLV-1-associated myelopathy/tropical spastic paraparesis." Nat Rev Dis Primers, (2015). 1: p. 15012.
- Enose-Akahata, Y. and Jacobson, S., "Immunovirological markers in HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP)." Retrovirology, (2019). 16(1): p. 35.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.