What a pleasure it is to think about a novel treatment for acne! Honestly, have you gotten excited learning that the “same old, same old” is now available in a cloth or foam?
Every dermatologist knows the rudiments of acne pathophysiology. The four main factors are increased sebum production, colonization with Proprionibacterium acnes, hypercornification of the pilosebaceous duct, and an inflammatory response. New insights have been forthcoming for each of these “pillars”. These have been summarized in the outstanding article by Suh and Kwon (1). A partial list follows:
- Sebum production: Pathways that regulate sebaceous gland biology and androgen metabolism may be considered therapeutically – there is potential to modulate both Toll-like receptor 2 activity and sebum production by altering the activity of 11-β-hydroxysteroid dehydrogenase type I (HSD11β1).
- Proprionibacterium acnes: DNA-based typing has demonstrated unique phylogenetic strains of acnes with some having an etiologic role in acne, while others are associated with health. Additionally, P.acnes biofilms are more common in sebaceous follicles of acne patients compared with controls, possibly playing a role in antibiotic resistance.
- Changes in the pilosebaceous duct: Toll-like receptor 2 is expressed in infundibular keratinocytes and sebaceous glands, activating the release of IL1-a from primary human keratinocytes in vitro
- Inflammatory response: Recent publications emphasize the role of inflammasomes (producing IL1-β), Th2 and Th7-IL-17 in the pathogenesis of acne.
- Other factors: diet, heredity, and oxidative stress may all contribute to the development of acne vulgaris.
Bissonette et al performed a clinical trial using the topical sebum inhibitor Olumacostat glasaretil (OG) in patients with moderate to severe facial acne vulgaris. OG inhibits acetyl-coenzyme A carboxylase, the enzyme responsible for the first, rate-limiting step in de novo fatty acid synthesis. OG inhibited in vitro human sebocyte lipid production and reduced in vivo sebaceous gland size in hamster ears. Safety and efficacy of OG 7.5% gel were evaluated. Patients were randomized (1:1) to twice-daily application of OG or vehicle for 12 weeks. Efficacy was measured through changes in lesion counts and improvement in acne severity scores. A total of 108 patients received OG (n = 53) or vehicle (n = 55); these groups had mean baseline counts of 29.7 and 28.6 inflammatory and 40.9 and 38.8 noninflammatory lesions, respectively. At week 12, OG treatment showed greater reductions from baseline in inflammatory lesions (-63.9% vs -45.9%; P = .0006) and noninflammatory lesions (-48.1% vs -28.8%; P = .0025), and more patients with greater than or equal to 2-grade improvement in investigator global assessment score (24.5% vs 7.3%; P = .0070) than vehicle. Application site adverse events (typically mild or moderate intensity – 4 patients had severe burning/stinging, 1 patient had severe erythema) were more common with OG. The authors concluded that OG was well tolerated and showed evidence of efficacy, suggesting further development is warranted (2).
Other potential topical inhibitors of sebum production include peroxisome proliferator-activated receptor activators, by inhibiting the release of lipids in the context of sebocyte apoptosis (3), or by inhibiting HSD11β1 via diminishing steroid-enhanced lipid synthesis and Toll-like receptor 2 expression (4).
With the trend of limiting systemic antibiotics, and the perpetual reluctance of many patients to use isotretinoin, perhaps the inhibition of sebum production will grease the path to more effective topical acne regimens.
- Suh DH, Kwon HH. What’s new in the physiopathology of acne? Br J Dermatol 2015; 172 Suppl 1: 13-9.
- Bissonnette R, et al. Olumacostat glasaretil, a novel topical sebum inhibitor, in the treatment of acne vulgaris: A phase IIa, multicenter, randomized, vehicle-controlled study. J Am Acad Dermatol 2017; 76: 33-9.
- Schuster M, et al. Peroxisome proliferator-activated receptor activators protect sebocytes from apoptosis: A new treatment modality for acne? Br J Dermatol 2011; 164: 182-6.
- Lee SE, et al. 11β-hydroxysteroid dehydrogenase type 1 is expressed in human sebaceous glands and regulates glucocorticoid-induced lipid synthesis and toll-like receptor 2 expression in SZ85 sebocytes. Br J Dermatol 2013; 168: 47-55.