Recent News 24 : What the future of acne therapy may look like

What the future of acne therapy may look like

Bacteriophages and CRISPR technology, and even an acne vaccine, could be on the horizon.

Bacteriophages and genetic modification using CRISPR technology could be acne treatments of the future, delegates heard at the Australasian College of Dermatologists annual scientific meeting in Brisbane earlier this month.

“In the next 12 months, this is going to be a really exciting space to watch,” said dermatologist Dr Lisa Byrom, senior lecturer at the University of Queensland.

Dr Byrom said she “absolutely” believed we would one day have acne cures, akin to how monoclonal antibodies have revolutionised the management of many conditions.

Her talk outlined several major advances in acne treatments in recent years, saying therapies targeting the microbiome had gained “tremendous interest”.

“We can’t talk about acne without talking about the microbiome,” Dr Byrom said. “Traditional treatments like antibiotics can reduce C. acnes but also disrupt the normal flora and microbiome of the skin, and of course, we’re facing growing concerns about antibacterial resistance.”

Bacteriophages

Bacteriophages, or viruses that eat bacteria, are a precision tool that may reduce bacteria-causing acne without wreaking havoc to healthy bacteria.

Dr Byrom pointed to a 2022 phase 1 study that found phage BX001, a topical bacterium-based cocktail that specifically reduced the Cutibacterium acnes bacterial load, reducing overall microbiome disruption.

“It offers perhaps a promising alternative to our antibacterial therapies,” she said, adding that such approaches could reduce antimicrobial resistance.

Gene modification and CRISPR

“CRISPR technology may revolutionise acne treatment by targeting those harmful strains of C. acnes without disrupting the microbiome,” Dr Byrom said.  

There was a 2024 case report of acne that was successfully managed with a topical spray containing live CRISPR-positive bacteria.

“It’s very, very early days, but this is the stuff that I get excited about,” she said.

Scientists were also exploring how to engineer C. acnes to produce neutrophil gelatinase-associated lipocalin (NGAL), a protein that mimicked isotretinoin’s effects on sebocytes. The study, published in Nature last year, found the spray reduced sebum production and triggered the destruction of sebum-producing cells.

“This living therapeutic offers a potential topical alternative to oral isotretinoin by using the skin’s own microbiome as its delivery system,” Dr Byrom said.

“This is fascinating, right? Could we develop an acne vaccine? I think this is probably one of the most exciting microbiome-based innovations in the acne pipeline at the moment.

“Unlike traditional treatments that add or remove bacteria, a vaccine would train the immune system to selectively neutralise acne-causing strains or their inflammatory byproducts without disturbing the rest of the skin microbiome.”

An acne vaccine

Dr Byrom pointed to a 2023 study in Nature Communications that pushed the idea of an acne vaccine forward. The paper identified two hyaluronidase variants produced by C. acnes; HylA was found in skin with acne and HylB was found in healthy skin.  

“Subtype A breaks down hyaluronic acid in a way that triggers inflammation – these are larger fragments – whilst subtype B produces more smaller fragments which have been shown to be more anti-inflammatory,” Dr Byrom said.

“Remarkably, there’s only one amino acid change that will flip type A’s behaviour into type B. So this discovery does open the door to vaccine development or biotherapeutics to target and treat acne.”

The authors of this “landmark” study have started doing mouse model studies which have been promising, but human studies had not yet been undertaken, Dr Byrom said.

Nevertheless, Sanofi had begun recruiting for 400 adults to take part in an acne vaccine study, which Dr Byrom said she hoped would provide data from next year.

AI for acne

AI had a potentially transformative role in dermatology, including acne diagnosis, grading severity and tracking treatment response, she said.

AcneDGNet, a deep learning model, can grade acne severity with 90% accuracy using smartphone pictures when compared with dermatologists’ diagnoses.

AI systems such as Q-learning models are developing personalised acne treatment plans too.

“They’re analysing images, genetic data and lifestyle factors to truly personalise patient plans, but also predict how someone’s acne is going to progress and how it’s going to respond,” Dr Byrom said.

“This is very exciting. I think this level of precision dermatology in tailoring our patient treatment plans is not going to replace us, this is going to enable us and enhance our treatments.”

Nevertheless, caution was needed. Dr Byrom warned many apps on the market weren’t well-validated, and dermatologists needed to be involved in the development in these tools.

These concerns were echoed by the College, who released a consensus statement on the minimum labelling requirements for Al-based software as medical device early last year.   

“So that we can use the AI appropriately and interpret the results correctly, it is critical that we can understand how the AI was developed and the data used to train and test it,” lead author Professor Victoria Mar, member of the College’s Digital Health Committee, said in a statement at the time.

“Like any product we use, the operating manual or product information should clearly explain when and how to use it safely and appropriately.”

What works now

Guidelines for acne management, published in the Journal of the American Academy of Dermatology last year, have been updated for the first time in around two decades.

They included a helpful patient information sheet that could be printed off, and covered five “good practice” statements for clinicians. These included the need for multimodal therapy, and reducing systemic antibiotics where possible.

Isotretinoin remained a good option, especially for patients with severe acne or who had failed standard treatment. Dr Byron highlighted that patients with psychosocial burden should be considered to have severe acne.

She said the TGA warning about the possible sexual side effects were not evidence-based, and instead were driven by patient reports through the UK’s NHS yellow card scheme which relied on patient-perceived associated events.

But there was no evidence of a biological mechanism, and she urged patients to read the Australasian College of Dermatologists’ position statement for up-to-date information on the drug’s side effects.

Dr Byrom noted around one in five patients would relapse after a course of isotretinoin, and patients were more likely to relapse if they start treatment at a younger age, had truncal acne or if the treatment was stopped stop treatment too soon after initial clearance.

New research from April this year suggested total cumulative dose overall – not daily dose – lowered relapse risk. Dr Byrom said the good news was that the average time to relapse was around six months, which meant doctors could counsel their patients on time frame and check in then to see if treatment needed to be fine-tuned.

Women were also a high-risk group, possibly due to underlying hormonal factors that needed to be addressed, she said.

This meant that treatment should not be limited to just a course of isotretinoin, but include additional dietary modification, topical vitamin A, topical antibiotic, or oral adjuncts such as the oral contraceptive pill or spironolactone, Dr Byrom said.

“I think, more and more, we’re heading towards a more individualised management programme for our patients. It’s not a one size fits all.”

Dr Haady Fallah, clinical senior lecturer at the University of Sydney, said there had been a paradigm shift in our understanding of the pathogenesis of acne.

“Part of the myth we need to we need to challenge is that acne is a microbial disease, that people have some sort of infection, and that over-cleansing can cure this,” Dr Fallah said in his presentation.

“I think that’s a point that we really emphasise to the patient; that this is not about dirty skin, and that you’re more likely to do damage by over-cleansing than you are to improve the acne,” he said.

The research now indicated inflammation was the key, instigating event and that epidermal hyperproliferation was more of a secondary phenomenon, said Dr Fallah, who runs a dedicated acne clinic in Sydney.  

There were three main drivers of inflammation: changes in skin microbiome, altered sebum composition and diet.

C. acnes usually protected the skin barrier, but it could become pathogenic if there was a loss of microbial diversity, which would lead to inflammation, he said.

Dr Fallah said that more sebum production wasn’t always correlated with acne severity. But patients with acne did have altered sebum composition, featuring increased squalene and reduced linoleic acid – which promotes inflammation.

But there was a reasonably simple intervention that could help: the Mediterranean diet.

Doctors didn’t need to recommend a complex and tailored diet, Dr Fallah said, instead observational research suggested a diet rich in plant-based foods could improve gut health and reduce inflammation, which would improve acne.

This was because gut dysbiosis and the IGF-1 pathways could influence sebum composition and inflammation, he said. Whole plant-based foods increased short-chain fatty acids, while processed foods reduced them.

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