ARA-290 12mg

ARA-290 is a compact peptide derived from the beta-helix domain of erythropoietin (EPO). Known for its broad biological effects, EPO primarily stimulates red blood cell production but also has additional roles. ARA-290 has been shown to enhance blood vessel formation, support cell survival, modify blood pressure, and provide neuroprotective benefits, particularly beneficial in diabetic neuropathy. It mirrors the neuroprotective and analgesic properties of EPO without promoting red blood cell synthesis.

Currently, ARA-290 has successfully completed phase II clinical trials and is poised to move into phase III trials, targeting a range of conditions including diabetes and certain autoimmune diseases like sarcoidosis. The peptide is particularly noted for its effectiveness in managing neuropathic pain and is being explored for its potential in enhancing wound healing in diabetes, acting as an immunomodulatory agent, and possibly treating systemic lupus erythematosus (SLE).

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Molecular Formula: C51H84N16021

Molecular Weight: 1257.3 g/mol

PubChem CID: 91810664

CAS No: 1208243-50-8

Synonyms: Cibinetide, PH-BSP

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Pain Perception and ARA-290’s Role

The immune system is known to influence pain perception, especially in conditions like diabetic neuropathy. Targeting specific immune receptors, like the Innate Repair Receptor (IRR), can reduce inflammation and neuropathic pain. ARA-290 not only impacts IRR but may also inhibit the TRPV1 channel, known for sensing heat and pain, suggesting its potential in managing pain from diabetes, MS, chemotherapy, and amputations.

Small Fiber Loss

Autoimmune diseases, notably sarcoidosis and diabetes, can lead to small fiber neuropathy—where tiny skin fibers that sense pain and temperature degenerate, causing symptoms like tingling or a sand-like feeling in shoes. ARA-290 treatment has been shown to increase these fibers and significantly reduce pain, indicating its effectiveness in nerve damage seen in various diseases including thyroid dysfunction and HIV.

Immune System and ARA-290

ARA-290, a peptide, binds to receptors on immune cells like macrophages and dendritic cells, influencing their function. It reduces pro-inflammatory cytokines (e.g., TNF-alpha, IL-6) from macrophages, easing disease severity and promoting better healing with fewer side effects. It may also modify antigen presentation by dendritic cells, potentially reducing organ rejection post-transplant.

Applications in Colitis and Lupus

ARA-290 shows promise in treating colitis, potentially easing chronic autoimmune conditions like Crohn’s disease with fewer side effects than current treatments. For systemic lupus erythematosus (SLE), it reduces harmful autoantibodies and kidney damage, suggesting a targeted treatment approach could significantly improve outcomes for SLE patients.

Tissue Protection

Mouse studies show that ARA-290 enhances the survival of transplanted islet cells by suppressing macrophage activation. Traditionally, transplanting insulin-producing islet cells has been seen as a potential cure for diabetes, providing more natural blood sugar regulation and reducing complications. However, their survival post-transplant has been limited. ARA-290’s ability to inhibit inflammatory cytokines like IL-6 and TNF-alpha may significantly extend islet cell longevity.

ARA-290 also binds to the Tissue Protection Receptor (TPR), mediating protection against inflammatory responses and helping to regulate the immune system. Unlike EPO, which has cardiovascular and hematopoietic side effects, ARA-290 minimizes apoptosis and harmful cytokine levels, leading to enhanced tissue protection and regeneration. This results in reduced morbidity and mortality, faster wound healing, less scarring, and quicker recovery from injuries.

Reducing Inflammatory Cytokines

Mouse studies reveal that ARA-290 enhances islet cell survival post-transplant by suppressing macrophage activation. Traditionally seen as a potential diabetes cure, islet cells offer more natural blood sugar control and thus reduce complications often seen even in well-managed diabetes. However, their survival has been brief post-transplant. ARA-290’s ability to inhibit cytokines like IL-6, IL-12, and TNF-alpha may significantly increase islet cell longevity.

Tissue Protection Mechanism

ARA-290 binds to the Tissue Protection Receptor (TPR), mitigating normal inflammatory responses and aiding immune regulation. Unlike EPO, which also binds to TPR but has cardiovascular and hematopoietic side effects, ARA-290 reduces apoptosis and inflammatory cytokine levels, enhancing tissue protection and regeneration. This results in decreased morbidity and mortality, faster wound healing, reduced scarring, and quicker recovery from injuries.

Vascular Health

Retinal ischemia, caused by various diseases, is a leading cause of blindness in developed countries. Protecting or regenerating retinal cells can significantly reduce disease burden. Studies in mice show that ARA-290 protects endothelial colony-forming cells (ECFCs) from inflammation, enhancing their survival and ability to repair and regenerate blood vessels.

Further research indicates that ARA-290 boosts ECFC proliferation, migration, and longevity across the vascular system, improving their capacity to target areas needing repair. This function could not only enhance the effects of endogenous ECFCs but also improve the ability of transplanted ECFCs to restore vessels and blood flow in ischemic tissues. If successful, ARA-290 could revolutionize medical therapy, enabling the transplantation of functional cells for tissue repair, hormone production, protein synthesis, and more.

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