2015年2月25日，首个干细胞治疗产品Holoclar获得欧盟委员会（EC）有条件批准，用于因（物理或化学因素所致）眼部灼伤导致的中度至重度角膜缘干细胞缺乏症（limbal stem-cell deficiency，LSCD）成人患者的治疗。
Holoclar由意大利凯西制药（Chiesi Farmaceutici）研发，是获批的首个含干细胞的先进治疗产品，也是首个用于治疗角膜缘干细胞缺乏症（LSCD）的产品。Holoclar不仅能够作为角膜移植的替代疗法，也可以在大范围眼部损伤的情况下增加角膜移植成功的概率。在临床试验中，Holoclar能够修复眼部角膜损伤，并改善或解决疼痛、畏光等症状，同时可改善患者的视敏度(visual acuity)。
Holoclar是一种活组织产品，类似于一个隐形眼镜，其活性物质为“离体扩增（ex-vivo）的包含干细胞的自体人角膜上皮细胞”，由取自患者角膜未受损区域的一小片活组织制备并在实验室利用细胞培养技术生长而成，可用于替代受损的角膜细胞。其中，角膜缘干细胞负责角膜上皮的连续再生和维持。通过在眼球重建干细胞储备，Holoclar能够启动正常的角膜细胞生长和维持。
Holoclar获批的具体适应症为：由物理或化学眼灼伤导致的单侧或双侧中度至重度角膜缘干细胞缺乏症（LSCD）（定义为：至少两个角膜象限存在浅层角膜新生血管，同时中央角膜受累，严重视力损害）。
患者接受Holoclar治疗前，需最少取1-2平方毫米完好的角膜缘（limbus）活组织。另外，Holoclar必须由经过培训的合格医生进行管理，并仅限于医院使用。 膜缘干细胞的缺乏使角膜上皮失去再生和修复的能力，引起角膜结膜上皮化、新生血管长入、慢性炎症、反复上皮缺损、基质瘢痕化以及角膜自溶和溃疡，若不进行治疗，该病最终可导致失明。
Europe approves Holoclar®, the first stem cell-based medicinal product
The European Commission has given Holoclar®, the first advanced therapy medicinal product (ATMP) containing stem cells, conditional marketing authorisation following a recommendation for approval by the European Medicines Agency.
Holoclar® uses a particular type of eye stem cell, called a limbal stem cell, to repair the cornea after injury; restoring sight. The work is a collaboration between an excellent public research center and a solid private pharmaceutical company. It has achieved an extraordinary result, entirely “Made in Italy”; the first stem cell-based medicinal product approved in the Western world.
This therapy has been brought to the clinic by an Italian team led by Professor Michele De Luca and Professor Graziella Pellegrini, both from the Centre for Regenerative Medicine (CMR, a donation of the bank Foundation Cassa di Risparmio di Modena) at the University of Modena and Reggio Emilia and Andrea Chiesi, Director of R&D Portfolio Management of Chiesi Farmaceutici S.p.A. and CEO of Holostem Terapie Avanzate, an University spin-off located in the CMR.
Using limbal stem cells to repair damaged cornea
The Holoclar® system uses stem cells to repair moderate to severe limbal stem cell deficiency. Limbal stem cells are located in a part of the eye called the limbus, which is found at the border between the sclera (white part of the eye) and the cornea (clear front part of the eye). The function of these limbal stem cells is to heal damage to the outer layer of the cornea. However injury, such as physical or chemical burns to the eyes can damage these cells, causing the cornea to deteriorate. This condition, known as limbal stem cell deficiency, can cause blindness, though other symptoms include: pain, sensitivity to light and inflammation.
The therapy works by taking a tiny portion (min 1-2mm2) of the undamaged limbus (where the limbal stem cells reside) and growing it in a laboratory using cell culture techniques. This produces a sheet of cornea that can then be transplanted back onto the eye. This technique is sufficient to restore sight in the absence of deep corneal stroma damage. Further, the combination of Holoclar® and corneal transplants can restore a normal cornea for, previously incurable, deep corneal burns. And, as only a small area of the patient’s eye is biopsied for this procedure, it does not involve surgery. As such, there is a reduced risk of damage to the rest of the healthy eye. Holoclar® thus gives a therapeutic chance to severe limbal stem cell deficiency that involves both eyes.
Professor Graziella Pellegrini, Coordinator of cell therapy at Centre for Regenerative Medicine, Modena, as well as director of R&D and co-founder of Holostem,explains further why Holoclar® is different to other treatments:
“This graft of epithelium – Holoclar®, looks like a kind of contact lens. It is transplanted into the patient and provides a long-term transparent cornea and full recovery of visual acuity, without causing any rejection reaction, because it consists of cells of the patient him/herself”.
This therapy, thanks to the registration by the European Commission, will soon be available to all European patients. It will be used to treat those 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 cases of assault with chemical agents.
The therapy is based on over 20 years of basic, preclinical and clinical research
Underlying this therapy is more than twenty years of excellence in research, conducted by a team [img_assist|nid=32232|title=|desc=|link=node|align=left|width=198|height=300]of internationally renowned scientists in the field of epithelial stem cell biology, aimed at clinical translation. European legislation states that stem cell cultures destined to be used in humans must be manufactured in GMP (Good Manufacturing Practice)-certified facilities. It was due to the investments of Chiesi Farmaceutici, that the Centre for Regenerative Medicine in Modena–where Holostem operates – was certified as GMP compliant.
Andrea Chiesi, Director of R&D Portfolio Management of Chiesi Farmaceutici S.p.A. and CEO of Holostem Terapie Avanzate gives his opinion on the approval of this therapy,
“This result 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”.
|
