"Cysteamine replaces hydroquinone as the new standard for melasma hyperpigmentation treatment"

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EADV 2017, 26th European Academy of Dermatology and Venereology Congress, September 13-17, 2017, in Geneva Switzerland

Independent researchers presented results at EADV 2017 setting cysteamine as the new standard of treatment for hyperpigmentation disorders :

  • Significant depigmenting effectiveness
  • Highly biocompatible and well tolerated
  • Non-cytotoxic, non-mutagenic, non-carcinogenic
  • Superior benefit/risk ratio compared to hydroquinone – and all other alternatives

Introduction

Physiologically present in human body, Cysteamine is a natural compound of the essential amino-acid L-cysteine derived from the co-enzyme A degradation. Already considered as a drug, Cysteamine was firstly introduced as radioprotective property by its effect against the formation of OH radicals and therefore used in clinical trials to treat patients’ radiation sickness. Over the years, the drug has been used in several conditions. One of the current use of Cysteamine concerns a rare disease cystinosis, in which cysteamine decreases intralysosomal cystine accumulation. Another interesting application regarding hyperpigmentation disorders, has recently showed the clinical efficacy of Cysteamine in melasma.

 

 

Chemical identity : Cysteamine as constituent of Co-enzyme A

 

Natural physiological level of cysteamine in mammalian cells

The natural physiological level of free cysteamine form at the natural physiological levels is well distributed in mammalian tissues, and a natural concentration of cysteamine is highest in mammalian milk.

 

Natural physiological level of cysteamine in mammalian cells

 

Safety profile

Various depigmenting agents are available and for most of them restricted by National Health Authorities (FDA and EMA), due to the poor Benefit/Risk ratio. Hydroquinone and its derivatives are the most popular depigmenting agent available to treat pigmentary disorders. However, it induces local side effects (irritation, permanent depigmentation…) and showed mutagenic and carcinogenic potentials. Other agents have been developed such as kojic acid, which is safer but with a lower efficacy than hydroquinone. Likewise, topical kojic acid can cause side effects (dermatitis, sensitization, and erythema) and mild carcinogenic potential as observed in some animal studies.

Cysteamine is a well-tolerated compound with a low toxicity which depends on, the dose and also the route of administration. At a higher oral dose (>200 mg/kg), cysteamine showed ulcerogenic properties. FDA reported abnormal skin/sweat/body odor, it was the most common of skin-related adverse reactions.

Many studies demonstrated the non-mutagenicity and non-carcinogenicity criteria of the agent. Interestingly Cysteamine may inhibit the mutagenic effect of some potent mutagens. In addition it may exert anti-cancer effect in several cancers, such as melanoma, in in vivo models.

Figure 1 - Safety profile of Cysteamine regarding its toxicity, mutagenicity and carcinogenicity.

The Cysteamine is compared to 4 depigmentating agents that have a tyrosinase inhibition activity (Azelaic acid, Hydroquinone, Kojic Acid and Retinoic Acid). This table shows the benefit (in green) of the five drugs (Cysteamine vs Azelaic acid, Hydroquinone, Kojic Acid and Retinoic Acid) by focusing on the depigmenting efficacy and the % of topical treatment ; and in red the risk reported in the literature for each drug (non exhaustive)

Risks Benefit Profile

As it appear s to have a better Benefit/Risk ratio, Cysteamine might be considered in the topical treatment in hyperpigmentation disorders, and should be much more compatible due to its physiological biosynthesis in mammalian cells.

Figure 2: Benefit / Risk ratio in hyperpigmentation disorders of five depigmenting agents : Cysteamine, Azelaic Acid, Hydroquinone, Kojic Acid and Retinoic Acid

Cysteamine has a very distinctive Benefit / Risk ratio for the treatment of hyperpigmentation disorders, superior to the four other depigmenting agents known to have tyrosinase inhibition activity : Azelaic Acid, Hydroquinone, Kojic Acid and Retinoic Acid.

Cysteamine has a much better compatibility due to its physiological biosynthesis in mammalian cells, a better efficacy profile as presented at the IPCC 2017 and a better safety profile regarding toxicity, mutagenicity and carcinogenicity.

Conclusion

Cysteamine is a highly bio-compatible active ingredient due to its physiological biosynthesis in mammalian cells. Cysteamine is a well-tolerated compound with a low toxicity and a well-known anti-mutagenicity and anti-carcinogenicity compound. Cysteamine has a better benefit/risk ratio than other alternative making it a new standard treatment for hyperpigmentation disorders. Cysteamine is a well-tolerated compound with a low toxicity. Many studies demonstrated the non-mutagenicity and non-carcinogenicity criteria of the drug, as well as its anti-mutagenicity and anti- carcinogenicity potentials suggest the molecule to be safe. As it appears to have a better Benefit/Risk ratio, Cysteamine might be considered in the topical treatment in hyperpigmentation disorders, and should be much more compatible due to its physiological biosynthesis in mammalian cells.

Access poster publication: "Cysteamine as the new standard for melasma hyperpigmentation treatment," EADV 2017

Source: EADV 2017, on 14.9.2017, by Ranesha Goorochurn, PhD

Independent studies conducted by the following groups:

  • LIBC, Cutaneous Biology Engineering and Laboratory, UMR 1098 INSERM, EFS BFC, University of Bourgogne Franche-Comté, Besançon, France
  • UMR U978 INSERM, Bobigny Cedex, France
  • ASIH, Signaling Adaptors in Hematology, University SPC, Paris 13, UFR-SMBH, Labex INFLAMEX, Bobigny Cedex, France
  • Dermo Dev Partners, Product Development expertise, Paris, France