BH4 ameliorates radiation-induced skin injury: an animal study and a phase II clinical trial

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Supplementary material for paper "BH4 ameliorates radiation-induced skin injury: an animal study and a phase II clinical trial"

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Radiation-induced skin injury from radiotherapy or accidents differs from traditional wounds due to impaired healing and prone to recurrence. However, there are currently limited treatments for preventing or mitigating this disease. In previous studies, we have identified several molecules and pathways involved in this disease. (J Eur Acad Dermatol Venereol. 2022;36(3): e207-e210. J Invest Dermatol. 2020; 140:94-102.J Invest Dermatol. 2017;137(10):2059–2068.Int J Radiat Oncol*Biol*Phys. 2016;95(2):751-60. Free Radical Biol & Med. 2014; 69:96-107.). Additionally, our research has shown that GCH1 can restore the disruption of cellular BH4 levels caused by radiation, thereby suppressing subsequent ROS generation. This finding highlights the crucial role of BH4 and its synthetic enzyme GCH1 in radiation-induced ROS and the resulting skin injury. (J Invest Dermatol. 2017;137(10):2059-68.). Nevertheless, the specific biological function of BH4 in radiation-induced skin injury remains to be elucidated. The novel aspects of this work that make it eligible for consideration in this journal are: 1) This report focuses on the role of GCH1, one of the crucial BH4 synthetic enzymes, in radiation-induced skin injury. Through our study using GCH1 cKO mice, we observed that skin tissues from GCH1-deficient (GCH1 cKO) mice were more susceptible to irradiation compared to those from wild-type mice. 2) Additionally, we conducted a phase II clinical trial to assess the safety and preliminary effectiveness of topical BH4 administration for radiation damage in patients undergoing radiotherapy (registration No. NCT05114226). Our findings indicate that BH4 provides protection against radiation-induced skin injury. Furthermore, the topical administration of BH4 has shown to be effective in protecting patients undergoing radiotherapy from radiation-induced skin injury.

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