Chronic
skin ulcers, such as
leg ulcers,
pressure sores and
diabetic foot ulcers, are a challenge to physicians and medical personnel and a cause of tremendous discomfort and ensuing loss of quality of life to the patients. Wound healing involves production and action of various
growth factors. A novel approach, distinct from the application of single
growth factors, is the administration of the macrophage stimulator macrophage-activating lipopeptide-2 (MALP-2). The rationale is based on the finding that macrophages are the main source of several
growth factors required for wound healing, which are sequentially released during this process.
MALP-2 has previously been shown to be effective in an established animal model with diabetic mice. The purpose of the present phase I study was to establish tolerability of
MALP-2 when applied into small cutaneous
wounds in human beings. Twelve patients (six females and six males; mean age 66.8 years; range 52-87 years) with different diagnoses were enrolled into the study. An artificial
wound was created with a 2-mm diameter skin biopsy punch and a volume of 30 microl
MALP-2 (0.125-1 microg) or vehicle control, respectively, was injected intracutaneously into the
wound and closed with a water-resistant transparent adhesive. Photos were taken daily from every patient up to 6 days, and skin biopsies were performed after 1 week from six patients. We could show in the present study for the first time that
MALP-2 caused a transient
erythema and was tolerated without any systemic side effects up to a dose of 1 microg per
wound in human beings. In healthy as well as in diabetic patients,
MALP-2 induced local
inflammation that faded after 48 h. The effectiveness of
MALP-2 in the healing of chronic
wounds in humans, e.g. in chronic
skin ulcers, such as
leg ulcers,
pressure sores and
diabetic foot ulcers, could now be addressed in further studies.