What is autophagy's potential to transform cosmetics applications?

In the first part of our interview with Keedon Park, CEO of Incospharm, we explored how autophagy has entered the forefront on cosmetics application in recent years following Professor Yoshinori Ohsumi of Tokyo Institute of Technology’s Nobel Prize accolade in for essential genes findings relating to autophagy​.

In our second instalment, we look at why Incospharm has centred its research initiatives on autophagy and how it has the power to transform skin care and cosmetic formulations and efficacy in the near future.

Identifying autophagy at ​

Founded in March 2011, Incospharm first designed a molecule called Aquatide, a peptide mimic of PCA, which was known as the natural moisturising factor (NMF).

PCA held onto water molecules to prevent them from escaping from the skin, but PCA was quite unstable, so the South Korean developer designed a peptide mimic that had stronger water retaining activities and higher stability.

It ran a cDNA array to investigate which genes were activated by Aquatide. Interestingly, Aquatide could activate anti-oxidation related genes such as peroxiredoxin 2, 3, selenoprotein K, stanniocalcin, aldehyde dehydrogenase 3A1, and sirtuin.

“We already knew sirtuin was a key protein in autophagic process in cells, so we continued exploring autophagy and skin,  right after the foundation of Incospharm,”​ explained Keedon Park, CEO, Incospharm.

Scientific reviews​

A review article was published in Cell in 2011 by Mizhushima and Komatsu, summarising the role of autophagy in individual organs of the human body, and the diseases that appear when autophagy is malfunctioning or suppressed.

Park goes on to explain that in the review, almost all organs were listed with the role of autophagy and the results when autophagy fails in the organ, except for skin. Interestingly, there were not many studies going on relating autophagy in skin in 2011. At that time, we already knew that Aquatide could activate the sirtuin 1 gene, so we decided to explore autophagy in the skin.

“I think we were one of the pioneers of studying what benefits autophagy have in skins,”​ Park relayed.

Aquatide has a lysine dimer backbone for easy modification or conjugation with other substances. It turned out that Aquatide is a very strong autophagy inducer in skin cells.

Active ingredient choice​

With its water retaining activity and anti-oxidative activity, Aquatide has proven to be an effective active ingredient for atopic dermatitis, acne, skin ageing, inflammation, and even pollutant-induced skin damages.

Today, Incospharm now has a library of about 300 different autophagy inducers, mostly peptide derivatives, and some natural extracts and small molecules.

Of those, Incospharm developed AdipoSol; an autophagy inducer effective for skin damaged by UV exposure, PolluxCD; an autophagy inducer effective for skin damaged by air pollutants such as PM2.5, and MelaTrepein; an autophagy inducer and par2 inhibitor that effectively degrades melanosomes transferred from melanocytes to keratinocytes.

The future of autophagy​

Commenting on how the company seeks to continue its autophagy development, Park added: “We are continuously developing new active ingredients that can activate autophagy in skin cells to reduce various skin problems such as psoriasis, hair loss, grey hair, inflammation, and environment-induced skin damages.”​

Incospharm is also collaborating with pharmaceutical companies developing new drugs for metabolic disorders such as diabetes mellitus type II, arthritis, and Alzheimer’s disease by screening our autophagy inducer library.