EU上市幹細胞產品: 角膜修復Holoclar, Holostem Terapie Avanzate, 借力GMP: Chiesi Farmaceutici

歐盟第一個上市的幹細胞產品-Holoclar 科技產業資訊室 - Pai 發表於 2015年3月18日新藥Holoclar細胞可治療角膜燒傷致盲的患者，也是歐盟核准的第一個商業化成功的產品，採集來源自臍帶血及骨髓。 Holoclar是歐盟核准的第一個商業化成功的產品，幹細胞採集來源自臍帶血及骨髓。Holoclar細胞可治療角膜燒傷致盲的患者。這個產品主要是由義大利摩德納大學再生醫學研究中心之團隊Graziella Pellegrin教授，克服了許多困難，最後終於將治療幹細胞成為市場產品。其方法是將患者未受傷眼睛的角膜緣(limbus)，取出少量幹細胞，在實驗室中培養，增加幹細胞之量，最後長成薄膜狀，然後由醫生取出患者因化學事故燒傷的眼角膜疤痕組織後，再植入幹細胞薄膜，結果就長成新的眼角膜組織，取代舊有受傷組織。因為是自體移植，沒有排斥問題，自1998年至2007年共治療106名患者，眼睛完全恢復視力有81人，成功率達76%，部分恢復者有14人，醫療效果到目前達10年。這個關鍵技術在於需培養約3000幹細胞，以提供大約1-2平方毫米的人纖維蛋白為支架之組織，以利幹細胞存活，在一年內能抑制血管再生進入角膜。這個產品是經過20年的努力，克服了許多的技術，及在社會環境惡劣下，仍努力堅持，最後終獲成功。這個幹細胞上市，對未來生技幹細胞的產業產品開發，具有很大的激勵作用。Holoclar現由義大利Chiesi Farmaceutical公司開發，為第一個治療因物理或化學因素所致眼部灼傷，導致中度或重度角膜緣幹細胞缺乏症(limbal Stem-cell Deficienny ,LSCO)之治療，在臨床試驗中發現也可解決或改善疼痛、畏光等症狀，同時亦可改善視覺靈敏度(visual acuity)。

Parma/Modena (Italy), February 20, 2015 – The European Commission has granted a conditional marketing authorization, under Regulation (EC) No 726/2004, to Holoclar®, an advanced therapy based on autologous stem cells and capable to restore the eyesight of patients with severe cornea damage. Holoclar® is manufactured by Holostem Terapie Avanzate (Holostem Advanced Therapies) – a spin-off of the University of Modena and Reggio Emilia – at the Centre for Regenerative Medicine "Stefano Ferrari" (CMR) of the same University."Holoclar is the very first medicinal product based on stem cells to be approved and formally registered in the Western world" – states Andrea Chiesi, Director of R&D Portfolio Management of Chiesi Farmaceutici S.p.A. and CEO of Holostem Terapie Avanzate. "This record – continues Andrea Chiesi – shows that the partnership between the public and private sectors is not only possible, but is probably the best strategy for the development of stem cell-based regenerative medicine, particularly when autologous cells are used. Holostem is now considered as a business model to translate into clinics the results obtained by scientific research in this field". Underlying Holoclar® are more than twenty years of excellence in research, conducted by a team of internationally renowned scientists in the field of epithelial stem cell biology aimed at clinical translation. European Directive 1394/2007 substantially equalizes advanced cell therapies to medicines and imposes, among other things, that cell cultures has to be manufactured only in GMP-certified facilities (GMP: Good Manufacturing Practice). Thanks to the investments of Chiesi Farmaceutici, the Centre for Regenerative Medicine in Modena – where Holostem operates – was certified as GMP compliant and continue to follow the path towards the registration of this newly developed advanced therapy."The authorization process has been long and complex, but the result achieved today shows that cells can be cultured according to pharmaceutical standards appropriate to guarantee safety and efficacy – adds Professor Michele De Luca, Scientific Director and co-founder of Holostem, as well as Director of the CMR of the University of Modena. – In addition, in a period of great confusion about the real therapeutic possibilities of stem cells, such as the one we are living in, being able to demonstrate that stem cells can be definitely safe and successful in a controlled clinical setting is more important than ever". Toexplain how Holoclar® works is Professor Graziella Pellegrini, Coordinator of cell therapy at CMR, as well as director of R&D and co-founder of Holostem, who authored, together with Professor De Luca, the research and designed the product development: "After developing cell cultures based on epithelial stem cells for the treatment of various disorders of the stratified epithelia – from the skin for full-thickness burns to the reconstruction of the urethra – we discovered that the stem cells that allow the regeneration of the cornea reside in a small area at the border between the cornea (the transparent part at the center of the eye) and the conjunctiva (the contiguous white part), which is called "the limbus". When thermal or chemical burns of the ocular surface damage irreversibly this stem cell reserve, the corneal surface – which in a healthy eye completely renews itself approximately every six/nine months – stops regenerating and the conjunctiva gradually begins to cover the cornea with a white coating, that prevents vision and causes chronic pain and inflammation. If in at least one of the eyes of the patient even a small residue of undamaged limbus is left, we are able to reconstruct in laboratory the epithelium that covers the corneal surface, thanks to the stem cells harvested through a 1-2 mm2 biopsy. This graft of epithelium – Holoclar®, precisely – that looks like a kind of contact lens, is then transplanted into the patient and allows to obtain a long-term transparent cornea and a full recovery of visual acuity, without causing any rejection reaction, because it consists of cells of the patient him/herself". This therapy, experimentally appliedfor the first timein humansin the nineties, and designated as orphan drug in 2008, thanks to the registration obtained today, in the near future will be available to all European patients who have suffered workplace injuries (caused, for example, by burnt lime, solvents or acids), domestic accidents (for example eye burns caused in adults and children by detergents or abrasive agents) or – as unfortunately reported by the press in the past few months – in the cases of assault with chemical agents. Meanwhile, the research in Modena does not stop. The next goal of the team of Emilian researchers and entrepreneurs is to develop new advanced therapy products, such as the gene therapy for the treatmen tof epidermolysis bullosa, or "Butterfly disease", to date used successfully in the first two patients ever. And to develop new experimental and clinical protocols using different stem cells of stratified epithelia, such as conjunctiva, urethra, oral mucosa and respiratory epithelia. Source: http://www.chiesigroup.com