Central centrifugal cicatricial alopecia (CCCA)

WEDNESDAY, Sept. 4, 2024 -- For patients with central centrifugal cicatricial alopecia (CCCA), which predominantly affects Black women, low-dose metformin is associated with symptomatic improvement and modulation of gene expression, according to a study published online Sept. 4 in JAMA Dermatology.Aaron Bao, from the Johns Hopkins University School of Medicine in Baltimore, and colleagues examined the association of low-dose oral metformin (500 mg extended-release, once daily) with clinical symptoms and scalp gene expression patterns in patients with CCCA in a retrospective clinical case series and transcriptomic analysis. The study included 12 Black female patients; transcriptomic analysis was performed in four patients.The researchers found that nine of the participants experienced improvement in disease, including scalp pain, inflammation, and/or pruritus after at least six months of metformin treatment, and six demonstrated clinical evidence of hair regrowth. Reversal of many prominent gene pathways previously identified in CCCA was reversed by the addition of metformin. Upregulation of pathways and genes involved in keratinization, epidermis development, and the hair cycle was seen in transcriptomic analysis, with concomitant downregulation of fibrosis-related pathways and genes. Reduced expression of helper T-cell 17 and epithelial-mesenchymal transition pathways and elevated adenosine monophosphate kinase signaling and keratin-associated proteins were seen after metformin treatment in a gene-set analysis."Adjuvant low-dose oral metformin was associated with symptomatic improvement, clinical evidence of hair regrowth, and modulation of gene expression profiles," the authors write.One author disclosed ties to the pharmaceutical industry and has a related patent pending.

Low-dose metformin linked to symptomatic improvement and modulation of gene expression in study involving 12 Black women

Metformin Eases Symptoms in Central Centrifugal Cicatricial Alopecia

Exploring the Role of Metformin in Treating CCCA 

In this episode of Topical Conversations, Crystal Aguh, MD, Associate Professor of Dermatology at Johns Hopkins School of Medicine, shares insights from her study investigating the potential benefits of metformin for patients with central centrifugal cicatricial alopecia (CCCA), a scarring alopecia that predominantly affects Black women.&nbsp;Understanding CCCA as a profibrotic disease&nbsp;CCCA is a form of permanent scarring alopecia, and previous research led by Dr Aguh demonstrated that it shares similarities with other fibrotic conditions including idiopathic pulmonary fibrosis, systemic sclerosis, and uterine fibroids. Notably, women with CCCA are 5 times more likely to have uterine fibroids than Black women without the condition. Based on these findings, Dr Aguh and her team aimed to explore potential treatment options that could reverse scarring.&nbsp;Metformin as a potential treatment&nbsp;Metformin, an FDA-approved treatment for diabetes, has been studied for its role in managing other fibrotic conditions. Dr Aguh noted that her initial research on the gene expression landscape of CCCA revealed a decreased expression of PRKAA2, a gene partially encoding adenosine monophosphate kinase (AMPK), which is the primary target of metformin. This discovery prompted the team to investigate whether metformin could impact the progression of CCCA.&nbsp;Case series: topical metformin shows promise&nbsp;In an initial case series, Dr Aguh applied topical metformin to patients with CCCA. Some patients experienced hair regrowth, and building on these findings, Dr Aguh introduced oral metformin into the treatment plan for 12 women with CCCA, administering a low dose of 500 mg once daily.&nbsp;Molecular and clinical impact&nbsp;Among the 12 women studied, 4 provided scalp tissue samples for analysis before and after oral metformin treatment. Bulk RNA sequencing revealed a near-reversal of several profibrotic pathways previously identified as hallmarks of CCCA. Pathways related to fibrosis decreased, while keratin-associated proteins—critical for hair growth—increased significantly. Clinically, 6 of the 12 patients experienced visible hair regrowth after 6 months of oral metformin use.&nbsp;A pilot study with future potential&nbsp;While the results are promising, Dr Aguh emphasizes that this is a pilot study. Larger clinical trials are necessary to quantify the benefits of metformin for CCCA and other scarring alopecias. Metformin is generally considered a safe medication, with common side effects such as weight loss and stomach upset, though stomach upset is less common in the extended-release formulation used in this study. Dr Aguh notes that patients with preexisting kidney disease require monitoring due to the risk of lactic acidosis.&nbsp;To learn more about metformin as a potential novel treatment option for reversing scarring and promoting hair regrowth in CCCA, read Dr Aguh’s full article here.

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