The development of effective therapies for diabetic foot ulcers (DFUs) requires navigating complex pathophysiology and demonstrating robust efficacy in predictive models. Ace Therapeutics provides integrated therapy development services spanning from target validation to preclinical efficacy and safety evaluation. Leveraging our deep understanding of diabetic foot ulcer pathology, validated animal models, and integrated evaluation platforms, we are committed to accelerating innovative therapy development for our clients while reducing development risks.

Current Status of Diabetic Foot Ulcer Therapy Development

• Conventional Therapies: Primarily consist of basic care (debridement, off-loading, anti-infection), surgical interventions (revascularization, amputation), and topical treatments (growth factors, moisturizing dressings). While addressing superficial symptoms, these approaches fail to reverse the core neurovascular pathology, resulting in high recurrence rates.
• Innovative Therapies: Therapeutic directions continue to expand, focusing on multi-mechanism synergistic interventions. These include neurorestorative agents (NGF agonists, neurotrophic factor delivery), revascularization formulations (VEGF/Ang-1 based therapeutics), anti-inflammatory and antioxidant drugs (NF-κB/NLRP3 inhibitors), stem cell/gene therapies, and smart wound dressings (drug-loaded sustained-release, pro-healing types), some of which have entered preclinical or early clinical stages.

Fig. 1 Potential features of functional biomaterials as ideal wound dressings for diabetic foot ulcer (DFU) healing. (Da Silva, J. et al., 2023)

Our Diabetic Foot Drug Development Service

We provide end-to-end services spanning key stages of therapy development to support multiple types of innovative treatments.

Target Identification and Validation Services

Identifying key therapeutic targets in diabetic foot ulcers to establish a scientific foundation for mechanism-driven therapy development.

• Primary Target Screening: Utilizing multi-omics analyses to identify potential targets (e.g., NGF, VEGF, TNF-α, MMPs) from core pathways including neurorepair, angiogenesis, anti-inflammation, and wound healing.
• Functional Validation: Using CRISPR/Cas9 gene editing, siRNA/shRNA silencing, and gene overexpression technologies to validate target functions in diabetic foot ulcer-relevant cellular models.
• Pathway Validation: Elucidating the mechanism of action of targets within core signaling pathways (PI3K/Akt, NF-κB, TGF-β).

Candidate Drug Screening for Diabetic Foot Ulcer

Rapidly identify candidate compounds with therapeutic potential for diabetic foot ulcers, shortening the hit-to-lead optimization timeline.

• In Vitro High-Throughput Screening: Large-scale activity screening of drug molecules using in vitro cell models and 3D wound organoid models.
• Activity Validation: Evaluation of candidate compounds' effects on core wound healing indicators, including cell proliferation/migration capacity, wound closure rate, angiogenesis potential, neurite outgrowth, and inflammatory factor suppression.
• Lead Compound Optimization Support: Providing structure-activity relationship (SAR) analysis, solubility/stability testing, preliminary cytotoxicity assessment, and determination of effective concentration ranges to facilitate the transformation of hit compounds into lead compounds.

Preclinical Pharmacodynamics Evaluation Services

We comprehensively evaluate the in vivo and in vitro efficacy of candidate drugs to elucidate their mechanism of action and therapeutic effects.

• In Vitro Efficacy Characterization: Employing techniques such as Western Blot, qPCR, and immunofluorescence to elucidate drug mechanisms of action (e.g., pathway regulation, biomarker alterations).
• In Vivo Efficacy Validation: Selecting appropriate diabetic foot ulcer animal models to assess comprehensive improvement in wound healing. Core endpoints include:
  • Morphological Metrics: Wound healing rate, healing time, re-epithelialization extent, granulation tissue quality;
  • Histological Metrics: Vessel density (CD31 staining), nerve fiber regeneration (NF-H staining), inflammatory cell infiltration, collagen deposition (Masson's trichrome staining);
  • Functional Metrics: Nerve conduction velocity, foot perfusion (Laser Doppler), restoration of pain threshold.

Preclinical Safety Assessment

• In Vitro Safety Screening: Cytotoxicity, genotoxicity, local irritation, and immunogenicity testing.
• In Vivo Safety Evaluation: Acute/subchronic toxicity studies, local safety assessment, and specialized safety testing.
• PK/PD Studies: Analysis of drug exposure levels, tissue distribution, and correlation with efficacy or safety in diabetic models

Diabetic Foot Drug Development Service Flow

• Needs Communication: Clarify client R&D objectives, technical requirements, timelines, and deliverables.
• Protocol Design: Develop a customized study plan that includes rationale for model selection (e.g., db/db for impaired healing, ischemic model for angiogenic therapies), defined primary and secondary endpoints relevant to DFU (e.g., time to 80% closure, histologic angiogenesis score), and statistical considerations.
• Contract Execution: Finalize protocol details, sign the service agreement, and kick off the project.
• Experimental Implementation: Conduct studies strictly adhering to the protocol, provide regular progress updates, and promptly address issues with adjustments as needed.
• Data Analysis: Upon completion of experiments, compile raw data and perform statistical analysis.
• Results Delivery: Provide a comprehensive report including integrated analysis of morphological, histological, and functional endpoints, with expert interpretation of findings in the context of DFU pathophysiology and clinical translation.

Ace Therapeutics is committed to helping clients overcome diabetic foot ulcer research challenges through professional and efficient preclinical services, advancing innovative products to bring new treatment hope to diabetic patients. For customized service solutions or technical consultation, please contact us.

References

1. Ogbeide, Omo A., et al. Evolving trends in the management of diabetic foot ulcers: A narrative review. Cureus. 16.7 (2024).
2. Da Silva, J., et al. Innovative functional biomaterials as therapeutic wound dressings for chronic diabetic foot ulcers. International journal of molecular sciences. 24.12 (2023): 9900.
3. Ramirez-Acuña, J. M., et al. Diabetic foot ulcers: current advances in antimicrobial therapies and emerging treatments. Antibiotics 8.4 (2019): 193.

• Diabetic Foot Pathological Research Service
• Diabetic Foot Ulcer Modeling Service
• Biomarker and Diagnostic Assay Development Services for Diabetic Foot Ulcers

• Mouse Models
• Assay Kits
• Antibodies
• Cell Lines & Lysates
• Proteins & Peptides
• Inhibitors & Activators