DiaPep277

Product Name: DiaPep277

Form: TFA salt

CAS No: 179822-83-4

Molar Mass: 2390.73

Chemical Formula: C106H180N28O34

Synonyms: F8778UWB0A

Storage: Store at -20℃

Sequence: VLGGGVALLRVIPALDSLTPANED

Application:

DiaPep277 (CAS: 179822-83-4) is a synthetic peptide-based immunomodulator used in the treatment of type 1 diabetes mellitus. It functions by modulating the immune response, specifically targeting T cells involved in the destruction of insulin-producing beta cells in the pancreas. DiaPep277 is derived from the sequence of heat shock protein 60 (HSP60), a protein involved in cellular stress response. It is believed to induce immune tolerance by stimulating regulatory T cells and shifting the immune response from a destructive to a regulatory phenotype. In pharmaceutical chemistry, DiaPep277 represents a novel approach to treating type 1 diabetes, offering the potential to preserve beta cell function and slow disease progression. Clinical trials have demonstrated promising results in terms of improving beta cell function, reducing insulin requirements, and achieving better glycemic control in patients with type 1 diabetes. Ongoing research continues to explore DiaPep277's mechanisms of action, optimal dosing regimens, and long-term efficacy, with the goal of providing a safe and effective treatment option for individuals with type 1 diabetes.

Current Research:

DiaPep277 is a 24-amino acid peptide derived from positions 437-460 of Heat Shock Protein 60 (HSP60), a molecular chaperone involved in protein folding and cellular stress responses. This peptide has garnered attention for its immune-modulatory effects in the context of autoimmune diseases, particularly Type 1 Diabetes (T1D). In animal models, specifically the Non-Obese Diabetic (NOD) mouse, DiaPep277 has been shown to arrest the progression of β-cell destruction, an autoimmune process central to the development of Type 1 Diabetes. By targeting diabetogenic T cells, DiaPep277 can modulate the immune system and prevent further damage to insulin-producing cells in the pancreas.

Mechanism of Action
DiaPep277 exerts its therapeutic effects by interacting with the immune system, specifically modulating T cell responses. The peptide binds to Major Histocompatibility Complex (MHC) class II molecules on antigen-presenting cells (APCs) and stimulates a regulatory T cell (Treg) response. This action leads to the suppression of diabetogenic T cells, which are responsible for the autoimmune destruction of pancreatic β-cells. By restoring immune tolerance, DiaPep277 helps in preventing the activation and proliferation of these pathogenic T cells, ultimately reducing the inflammatory response that drives β-cell destruction in Type 1 Diabetes. Additionally, this immune modulation helps preserve the function of pancreatic β-cells, which are critical for insulin production.

Indications and Uses
DiaPep277 is primarily being developed for Type 1 Diabetes (T1D), specifically for preventing the progression of the disease in individuals who are at risk or in the early stages of β-cell destruction. It is being investigated as an immunotherapy aimed at modulating the immune response to stop or slow the autoimmune attack on the pancreas. By targeting autoimmune T cells, DiaPep277 holds potential not only as a preventive treatment but also as a disease-modifying therapy in patients with established Type 1 Diabetes. Furthermore, its immune-modulatory properties may have broader applications in other autoimmune disorders, where inappropriate T cell activation is a contributing factor.

Efficacy and Clinical Benefits
In animal models, particularly NOD mice, DiaPep277 has been shown to effectively arrest the progression of β-cell destruction and prevent the onset of Type 1 Diabetes. This effect is achieved through the peptide's ability to modulate immune responses and promote the development of regulatory T cells, which play a key role in maintaining immune tolerance. In clinical trials, DiaPep277 has demonstrated potential in reducing the rate of β-cell loss and preserving insulin production in individuals at risk for Type 1 Diabetes. By targeting the root cause of the disease, DiaPep277 aims to halt the autoimmune destruction of β-cells, offering a novel approach to treating or preventing Type 1 Diabetes in high-risk populations.

Safety and Tolerability
DiaPep277 has shown a favorable safety profile in preclinical and early clinical studies. The peptide is generally well-tolerated, with no significant adverse effects observed in animal models. In human trials, the most common side effects have been mild, including injection site reactions and occasional mild flu-like symptoms. Given its targeted mechanism of action on the immune system, DiaPep277 is not expected to cause broad immunosuppression or increase the risk of infections, as it specifically modulates the T cell response rather than suppressing the entire immune system. Ongoing clinical trials are monitoring for long-term safety and assessing the potential for immune system imbalance or other rare immune-related events.

Advantages and Limitations
The main advantage of DiaPep277 lies in its ability to halt the autoimmune process that drives the progression of Type 1 Diabetes. By specifically targeting diabetogenic T cells, DiaPep277 represents a disease-modifying therapy that aims to prevent or slow the progression of the disease, potentially preserving β-cell function and insulin production. Unlike traditional immunosuppressive therapies, which may have broad and undesired effects on the immune system, DiaPep277 offers a more targeted approach to immune modulation. However, its limitations include the need for regular injections and the fact that it is primarily being tested in prediabetic or early-stage Type 1 Diabetes patients. More data is needed to establish its long-term efficacy, particularly in more advanced stages of the disease or in individuals already dependent on insulin.

Future Directions
The future of DiaPep277 lies in its continued clinical development, particularly for individuals with early-stage Type 1 Diabetes or those at high risk for the disease. Ongoing trials will focus on confirming its ability to preserve β-cell function, delay the onset of insulin dependence, and modify the disease course in both children and adults. Additionally, researchers are exploring its potential in combination therapies with other immunomodulatory treatments to enhance its efficacy. Expanding the use of DiaPep277 to other autoimmune diseases, where immune tolerance needs to be restored, represents another exciting direction for future research.

Reference:

Raz, I., Ziegler, A. G., Linn, T., Schernthaner, G., Bonnici, F., Distiller, L. A., ... & DIA-AID 1 writing group. (2014). Treatment of recent-onset type 1 diabetic patients with DiaPep277: results of a double-blind, placebo-controlled, randomized phase 3 trial. Diabetes Care, 37(5), 1392-1400.

Elias, D., Avron, A., Tamir, M., & Raz, I. (2006). DiaPep277 Preserves Endogenous Insulin Production by Immunomodulation in Type 1 Diabetes. Annals of the New York Academy of Sciences, 1079(1), 340-344.