Xeroderma Pigmentosum

Researchers decode repair mechanism during transcription of genetic information. Cockayne syndrome is a severe autosomal recessive disorder caused by defective DNA repair mechanisms. People with the disease have much reduced life expectancy and suffer from facial deformities; growth failure; neurological, cognitive, and sensory impairments; bone, joint, and muscle deformities; kidney problems; and premature aging. Like xeroderma pigmentosum (XP), Cockayne syndrome (CS) is a disease where elements of nucleotide excision repair (NER) do not work properly. The purpose of this repair mechanism is to remove DNA damage caused by ultraviolet (UV) light, chemicals, and various other environmental factors. Researchers from the group of biochemist Professor Julian Stingele from LMU's Gene Center Munich have now uncovered important details about the role of the CSB/ERCC6 and CSA/ERCC8 genes involved in Cockayne syndrome. These genes encode two enzymes associated with DNA repair. The results of their work have been published in the journal Nature Cell Biology. "Our data point to a new, previously unknown function of these two genes and their gene products in the repair of covalent DNA-protein interactions in the course of transcription," reports Stingele, referring to the cytotoxic, biologically undesirable crosslinking of proteins to DNA. An obstacle for transcription In collaboration with researchers from the University of Cambridge, the scientists demonstrated that DNA-protein crosslinks present a physical obstacle to further transcription. Arresting transcription brings CS proteins to the blockade sites. "Our results indicate that CSB and CSA then initiate the transcription-coupled repair of the toxic DNA-protein crosslinks," says Stingele. "This previously unrecognized cellular function of CS proteins leads to the marking of the DNA damage -- and thence to its enzymatic breakdown." The study also revealed that this newly discovered function of CS proteins works independently of classic TC-NER (transcription-coupled nucleotide excision repair) enzymes, which are deployed, among other things, for repairing DNA damage caused by UV light -- and the absence of which leads to xeroderma pigmentosum. "The fact that CS proteins have additional functions is noteworthy. This discovery could help to explain the pathological differences between xeroderma pigmentosum and Cockayne syndrome," says Stingele. CS is a more severe and more multifaceted disorder than XP, with complex and incompletely understood causes. As their next step, Stingele's research group plans to decode the exact process of CS-protein-mediated repair.

DÜSSELDORF, Germany, March 28, 2024 (GLOBE NEWSWIRE) -- Pioneering biopharmaceutical company CLINUVEL yesterday hosted a wide-ranging market briefing discussing its novel drug SCENESSE® (afamelanotide) and the future of photomedicine. Over 70 guests discussed the Company’s unique history and future growth potential at an invitation-only event in Düsseldorf. Managing Director and CEO, Dr Philippe Wolgen shared the Company’s success in establishing profitability over the past seven financial years, building a strong balance sheet, commercialising the innovative melanocortin drug SCENESSE®, and plans to bring melanocortin technology to wider audiences with unmet needs. CLINUVEL is now investing heavily in R&D with an ambitious clinical pipeline, including a phase III clinical trial for the pigment loss disorder vitiligo. A case study presented at the American Academy of Dermatology Meeting on 9 March highlighted the systemic repigmentation of the skin of a female patient from the combination of SCENESSE® and phototherapy (light treatment). An estimated 45m individuals live with vitiligo globally, with no effective treatments for widespread depigmentation. The Company’s aspirations stretch beyond the clinical, with Dr Wolgen expanding upon the goal of making CLINUVEL a household name with the introduction of its PhotoCosmetics lines, incorporating novel melanocortin peptides. The consumer skincare lines are translating the Company’s targeted science into innovative products for the wider population. The lines were introduced to key US investors and celebrities during an intimate event at the home of Lady Gaga and longtime shareholder Michael Polansky in Malibu last month, resulting in positive feedback, a new international audience and anticipation for launch. “The potential of CLINUVEL to translate its expertise in melanocortins to address unmet needs in a range of conditions and as PhotoCosmetics underlies the future potential of the Company,” Dr Wolgen said. “German investors have been pivotal in supporting our work thus far and we hope to share our success with the wider investment community.” About The CLINUVEL Group: CLINUVEL is a public biopharmaceutical company whose pioneering melanocortin technology has revolutionised the field of photomedicine. Over the last 25 years, CLINUVEL’s work has furthered scientific knowledge, delivered breakthroughs in medical technology and transformed patients’ lives. The Company has developed and commercialised SCENESSE® (afamelanotide), the only approved treatment in the world for the prevention of phototoxicity in adult patients with EPP. The treatment was approved for use by the US FDA in 2019 and is also approved for commercial distribution in Europe, Israel and Australia. CLINUVEL is conducting clinical trials to assess the efficacy and safety of its melanocortin technology in treating severe disorders including xeroderma pigmentosum (XP), vitiligo and arterial ischemic stroke. In 2023 it announced its expansion into skincare with the introduction of its first PhotoCosmetic product CYACÊLLE, a polychromatic solar screen. Contact: Tel: +61 3 9660 4900 Fax: +61 3 9660 4909 Email: mail@clinuvel.com Australia (Head Office), Level 22, 535 Bourke Street, Melbourne, Victoria, 3000, Australia For more information visit Instagram: @clinuvel_pharmaceuticals Twitter: @ClinuvelNews Facebook: @Clinuvel Media Contact: lachlan.hay@clinuvel.com

MALIBU, Calif., March 04, 2024 (GLOBE NEWSWIRE) -- Leading biotech company CLINUVEL last week joined an intimate event bringing together California’s most prolific investors and philanthropists at the Malibu home of Lady Gaga and Michael Polansky. The event, hosted by Lady Gaga and Mr. Polansky, and Sean Parker and Alexandra Parker, shone a light on the groundbreaking work of CLINUVEL, a global biopharmaceutical firm whose cutting-edge melanocortin therapies transform the lives of patients at the highest risk of photodamage and skin cancer. Mr. Parker and Mr. Polansky have supported CLINUVEL for more than 15 years, finding alignment between the Company’s pioneering approach to medicine and the boundary-pushing work of the Parker Institute for Cancer Immunotherapy which works to revolutionise healthcare. Over a family-style dinner by chef Evan Funke of Los Angeles hotspot Felix Trattoria, and a performance by Grammy-winning Attacca Quartet, the hosts shared how CLINUVEL’s treatments herald a new era for the treatment of light-related conditions. The Group’s CEO Dr. Philippe Wolgen also unveiled what is next for the most exciting biopharmaceutical firm in the field of photomedicine today. The future of photomedicine For 25 years, CLINUVEL introduced a proof of concept by treating groups of patients whose needs had been overlooked by the pharmaceutical industry. These include the genetic disorders erythropoietic protoporphyria (EPP), xeroderma pigmentosum (XP) and the skin disorder vitiligo, when people lose their pigmentation. In 2014 CLINUVEL developed the only approved treatment in the world for EPP, accelerating CLINUVEL’s evolution into a profitable, self-sustaining and dynamic company. Now the Company is exploring the vast potential of its technology: how can CLINUVEL’s unique knowledge of melanocortins be scaled up to treat widespread health conditions that affect the skin, brain and nervous system? Beyond the world of pharmaceuticals, CLINUVEL’s technology has the power to disrupt the skincare market. After 43 years of photomedicine research, the Company is launching PhotoCosmetics, a range of advanced skincare products based on a group of peptides known as melanocortins. Revolutionising healthcare for those in needPhilanthropy is central to the work of Lady Gaga and Michael Polansky, Sean Parker and Alexandra Parker. CLINUVEL shares their passion for creating long-lasting change and radically improving patients’ lives. At the event in Malibu, CLINUVEL announced the Photomedicine Foundation, which will count Mr Polansky as a trustee. The initiative will help those most affected by debilitating conditions related to the sun. Through the Foundation, CLINUVEL is taking its world-leading expertise directly to communities who cannot afford care or treatment. The foundation’s mission is to support vulnerable patients at extreme risk of photodamage and skin cancer in Africa, Middle East and Latin America. Michael Polansky said: “It’s critical that investors strive to find companies whose missions extend beyond profitability, by supporting the development of technologies that can drive meaningful and sustained improvement to human life. CLINUVEL is an example of a company that aims to improve human health and I am delighted to become a trustee of the Photomedicine Foundation, which will play a vital role in improving the lives of individuals with light-related conditions who cannot access life-saving medical care.” Sean Parker said: “CLINUVEL is one of the most innovative Life Sciences companies that exists today with a management that has the patience to see through long development. Both its groundbreaking melanocortin technology and long-term business plan will disrupt the world of biopharmaceuticals and luxury skincare. The Photomedicine Foundation is a welcome addition to a company on a path to growth unlike any other.” CLINUVEL’s CEO, Dr. Philippe Wolgen said: “Sean Parker and Michael Polansky are unafraid to rip up the rulebook in their mission to advance science and improve global health. CLINUVEL is grateful to have their support as we translate our pharmaceutical technology into PhotoCosmetics and give back to underserved communities. A bright future looms for CLINUVEL.” About The CLINUVEL Group: CLINUVEL is a public biopharmaceutical company whose pioneering melanocortin technology has revolutionised the field of photomedicine. Over the last 25 years, CLINUVEL’s work has furthered scientific knowledge, delivered breakthroughs in medical technology and transformed patients’ lives. The Company has developed and commercialised SCENESSE® (afamelanotide), the only approved treatment in the world for the prevention of phototoxicity in adult patients with EPP. The treatment was approved for use by the US FDA in 2019 and is also approved for commercial distribution in Europe, Israel and Australia. CLINUVEL is conducting clinical trials to assess the efficacy and safety of its melanocortin technology in treating severe disorders including xeroderma pigmentosum (XP), vitiligo and arterial ischemic stroke. In 2023 it announced its expansion into skincare with the introduction of its first PhotoCosmetic product CYACÊLLE, a polychromatic solar screen. For more information visit www.clinuvel.comInstagram:@clinuvel_pharmaceuticals @clinuvelDNATwitter:@ClinuvelNewsFacebook:@Clinuvel