Use of complement inhibition to improve wound healing

Wound healing is a huge clinical problem. Problematic outcomes of skin wounds can range from under-healing (e.g., chronic/non-healing wounds) to over-healing (e.g., scarring). Healing via scarring has major consequences for human health: scarring can cause disfigurement, functional loss, and reduced quality of life. Despite the substantial clinical burden scars impose, there are no current therapies that induce scar-free healing in humans. Existing methods for reducing scarring are limited to tension-offloading dressings, which can be unwieldy, may be difficult to apply depending on the location of the injury, and have no potential for translation to non-skin fibroses. Existing methods for improving healing of chronic wounds are limited to conservative treatment or hyperbaric oxygen therapy, which is expensive, inconvenient, resource-intensive, and not available to most patients.

Stanford inventors have identified complement pathway inhibition as an approach for improving wound healing outcomes, including accelerating wound repair, decreased scarring/fibrosis, and increased wound regeneration. They investigated the genetic profile of MRL mice, a strain of laboratory mice with known super-healing properties, including the ability to fully regeneratively heal through-and-through ear punch wounds. Regenerative ear healing in this strain includes features such as regeneration of key tissue types (including cartilage and normal/unwounded-like skin) as well as accelerated/enhanced wound closure and re-epithelialization. They identified genes with patterns of cis-regulation that were unique to MRL ear wounds, which are candidate drivers of regenerative/enhanced healing. Complement factor H (CFH) - a natural inhibitor of the complement pathway – was identified as the gene specifically upregulated in MRL ear wounds, suggesting that complement inhibitory activity may play a role in wound regeneration/enhanced wound healing. Inventors found that CFH treatment improved wound healing, leading to: accelerated wound closure and accelerated/more complete re-epithelialization; less-fibrotic tissue ultrastructure; evidence of hair follicle regeneration on histology, and decreased scar thickness indicating decreased scarring/fibrosis. The method of complement inhibition could improve wound healing by reducing scarring/promoting regeneration or accelerating/enhancing wound repair.