Study Suggests MMP2 Mediates Retinoid Efficacy in Photo-aging

Anna L. Chien, MD

Results from new mechanistic studies into the treatment of moderate to severe facial photodamage found no significant difference in efficacy between topical tretinoin precursors (TTP) and tretinoin 0.02% (RA).

The studies also suggested that matrix metalloproteinases could function as a possible mediator of retinoid efficacy in photoaging.

Despite retinoids being widely considered as the “criterion standard” for topical management of photo-damage, the use of topicals have been associated with increased instances of erythema, pruritus, stinging, burning, and scaling.

Given these adverse reactions, alternate forms of topical retinoids have been considered, including natural precursors of tretinoin such as retinol. However, limited evidence on the efficacy of these precursor therapies exist.

As such, an investigative team led by Anna L. Chien, MD, Department of Dermatology at Johns Hopkins, Maryland, attempted to identify key drivers of retinoid efficacy through the evaluation if target gene expression alongside clinical efficacy.

The team conducted an exploratory randomized clinical trial evaluation of 1.1% TTP- which contained retinol, retinyl, acetate, and retinyl palmitate- and topical 0.01% RA for the treatment of moderate to severe photodamage.

The study was conducted over the course of 24 weeks from November 2010 to December 2011, with a data analysis being performed from January 2012 to December 2021.

At this time, patients with at least moderate facial photodamage were enrolled in the single-center, randomized, parallel-arm study. Patients were 35 years and older with good general health, Fitzpatrick skin phototype I to V, the ability to undergo biopsies, and the willingness to use only the provided products and drugs featured in the study.

Patients with preexisting or dormant dermatologic conditions and cosmetic procedures performed on treatment areas were excluded.

Those who were eligible for inclusion were randomized with 1:1 ratio before being given either 1.1% TTP or 0.02% tretinoin.

From there, investigators took digital photographs ahead of several in-person evaluations at baseline and weeks 4, 12, 18, and 24, in which a treatment-blinded dermatologist evaluated patients for degree of facial photodamage, signs of cutaneous irritation, global assessments of improvement, patient-reported outcomes, and adverse events.

The Findings

A total of 24 participants aged 40-84 years with Fitzpatrick skin phototypes I-III were included in the study, 22 of whom were women. A total of 20 patients completed the entire.

By the end of the study, investigators observed no significant difference in Griffiths photoaging scores among patients from either treatment group, though treatment with TTP was associated with erythema 6 times less frequently than RA (11% versus 64%) (P=0,1).

Notably, MMP2 mRNA- which encodes a type IV collagenase- was significantly reduced in TTP-treated samples (P = .02), and changes in MMP2 were strongly correlated with changes in fine wrinkles (P = .01).

Additionally, patients with severe baseline wrinkles exhibited greater improvements (P < .001), which were also indicated in MMP2 mRNA (P<.001).

Though no significant differences in therapies were observed in the study, the investigative team felt the findings associated with MMP2 expression “highlight the potential role that MMP2 may play” in the mediation of retinoid efficacy in photoaging.

“Larger studies with more diverse patients should be pursued to validate these findings in a broader population,” the team wrote.

The study, "Biomarkers of Tretinoin Precursors and Tretinoin Efficacy in Patients With Moderate to Severe Facial Photodamage," was published online in JAMA Dermatology.