What is the ARA-290 peptide?
Erythropoietin (EPO) is a kidney-derived glycoprotein that promotes blood vessel growth, tissue repair, cell survival, neuroprotection in diabetic neuropathy, and alters blood pressure. ARA-290 is a peptide derived from the beta-helix domain of EPO. ARA-290 simulates the pain relief and neuroprotective effects of EPO without promoting blood vessel formation. The peptide has completed phase II trials, and phase III trials will begin soon for diabetes and neuropathic sarcoidosis. It is being evaluated for its potential for neuropathic wound healing, immunomodulator, and treatment for Systemic Lupus Erythematosus (SLE).
AKA: Cibinetide, PH-BSP
Molecular Formula: C51H84N16O21
Molecular Weight: 1257.3 g/mol
CAS Number: 1208243-50-8
The health of blood vessels
Retinal ischemia can be caused due to various diseases and ultimately leads to damage to retinal epithelial cells. The peptide protects endothelial colony-forming cells to repair the blood vessels and rebuild the damaged tissue. Mice models have revealed the peptide to significantly enhance the proliferation, migration, and homing movement of blood cells as soon as the treatment begins. Hence, ARA-290 helps rebuild vasculature and speeds up the transplant’s success.
Reduction of inflammatory cytokines
ARA-290 inhibits macrophage activation. Thus it enhances the survival and proliferation of transplanted islet cells in diabetic patients. Islet cell transplant has been considered the holy grail of endocrinology for the treatment of chronic diabetes. Islet cell transplant allows for physiological control of blood sugar and helps to avoid the long-term adverse effects of insulin usage. However, the host immune response leads to the death of the transplanted islet cells. ARA-290 suppresses the pro-inflammatory cytokines such as IL-6, IL-2, and TNF-Alpha and allows for an acceptance of the graft.
ARA-290 has been observed to bind to the tissue-protective receptor (TPR) on the cell surface and mediate a protective response against inflammatory cytokines, thereby modulating the immune system response. EPO can also interact with TPR but is not a suitable drug candidate due to its cardiovascular and hematopoietic side effects. ARA-290 mediates the positive responses of EPO while avoiding the adverse effects. This results in reduced cellular apoptosis and lower levels of inflammatory cytokines. Thus the tissue survival and proliferation significantly improve. This function leads to faster wound healing, recovery, decreased mortality and morbidity, reduced scar formation, and rapid post-injury recovery of function.
Regulation of immune system
TPRs are prevalent on immune cell surfaces, such as T lymphocytes, mast cells, macrophages, and dendritic cells. Increasing scientific evidence proves that ARA-290 and similar groups of peptides bind to the receptor directly affect their function. TPR activation by ARA-290 leads to macrophage inactivation and lowering of inflammatory cytokines. This might decrease pathogen clearance in infection but overall lessen the disease build-up. With the macrophage chemokine pathway being restricted by TPR-ARA-290, resident macrophages get recruited to injury sites, leading to faster tissue healing and reduced side effects.
ARA-290 modifies antigen presentation by dendritic cells to T lymphocytes. Thereby it plays a pivotal role in modulating the adaptive immune response. Adaptive immunity is the key determinant of graft acceptance/rejection. Hence, peptides such as ARA-290 help to fine-tune the immune response to allow kidney, heart, and other experimental grafts.
One of the most promising applications of ARA-290 is immune modulation, especially in settings of autoimmune disorders like Colitis. Colitis can not only be caused by infection but also by autoimmune triggers. Immune modulators will help to significantly improve the treatment regimen compared to injectable alternatives with diverse side effects.
Another significant application of ARA-290 is in the treatment of SLE-Systemic Lupus Erythematosus (SLE). Treatment with ARA-290 significantly reduces the level of autoantibodies like ANA and anti-ds DNA. The peptide thus helps to control the chances of kidney damage and renal failure from SLE.
The immune system is known to regulate the sensation of pain, especially neuropathic pain. Neuropathic pain is very difficult to treat, like in diabetes. Targeting the innate repair receptor (IRR) helps to alleviate the pain. ARA-290 has been shown to bind to IRR and therefore proves to be of value. The peptide not only binds to IRR but also inhibits TRPV1 channel activity. TRPV1channel is also known as capsaicin receptor, which induces the perception of heat associated with neuropathic pain. Hence the peptide can control pain associated with amputation, chemotherapy, multiple sclerosis, and diabetes.
Small nerve fiber loss is prevalent in diseases like HIV, diabetes, celiac disease, thyroid dysfunction, etc. The small nerve fibers in the skin lead to pain and heat sensation. The onset of neuropathy leads to a burning sensation in the region affected. The peptide has proven fruitful in controlling neuropathy.
The peptide is a derivative of EPO. Interestingly it shows the positive effects of EPO and overcomes its side effects as well. ARA-290 is significant in controlling neuropathic pain, promotes wound healing, modulates immune response and pro-inflammatory cytokines, vascularization during ischemic insults. It has thus completed Phase II trials and moved to Phase III to treat diabetic and sarcoid neuropathy. It is being considered in multiple other diseases like HIV, multiple sclerosis, systemic lupus erythematosus, and likes. It can thus be considered as the wonder drug.