First Stem Cell Therapy Recommended for Approval in European Union

The EMA, which is short for the European Medicines Agency, has recommended approval for a treatment called Holoclar.  Holoclar is the first therapy product that contains stem cells to be recommended for approval in the European Union (EU). Holoclar is being marketed as a treatment for moderate to severe limbal stem cell deficiency (LSCD) due to physical or chemical burns to the eye in adults. In fact, Holoclar is the first medicine recommended for LSCD, a condition that can result in blindness.

Holoclar can be transplanted into the eye after removal of the corneal epithelium (the outer layer of the cornea). Holoclar is made from a biopsy taken from a small, undamaged area of the patient’s cornea. These limbal stem cells are then grown in the laboratory using cell culture techniques. Holoclar is a potential alternative to transplantation for replacing altered corneal epithelium. Clnical trials with Holoclar have been shown to increase the chances of a successful corneal transplant where the injury has caused extensive eye damage. Holoclar is produced by Chiesi, a pharmaceutical company based in Parma, Italy.

The recommendation to approve Holoclar was made by the EMA’s Committee for Medicinal Products for Human Use (CHMP). CHMP made their recommendation on basis of the benefits of Holoclar, which are its ability to repair the damaged ocular surface, to improve or resolve symptoms of pain, photophobia and burning and to improve the patient’s visual acuity. This assessment was the work of the Committee for Advanced Therapies (CAT). The approved indication for Holoclar is: “Treatment of adult patients with moderate to severe limbal stem cell deficiency (defined by the presence of superficial corneal neovascularisation in at least two corneal quadrants, with central corneal involvement, and severely impaired visual acuity), unilateral or bilateral, due to physical or chemical ocular burns. A minimum of 1-2 square millimeters of undamaged limbus is required for biopsy.” CAT and CHMP considered that Holoclar provided a first treatment option for LSCD and recommended a conditional marketing authorization. The authorization is conditional because the clinical data available for Holoclar is based on studies that are ongoing as treated patients are watched after their eye surgery. This the data collection is not yet comprehensive, and additional study on the use of Holoclar needs to be conducted.

The opinion adopted by the CHMP at its December 2014 meeting is an intermediary step on Holoclar’s path to patient access. The CHMP opinion will now be sent to the European Commission for a decision on an EU-wide marketing authorization.

Discovery of New Stem Cell Class Might Accelerate Research

An international team of scientists has discovered a new class of stem cell. This project consisted of a massive collaboration between over 50 scientists on four continents, that has been affectionately named, “Project Grandiose.” This new class of stem cells, known as a F-class cell, opens new and exciting avenues for generating designer cells that could be safer and more efficiently used in therapy.

Andras Nagy, Ph.D., from the University of Toronto’s Institute of Medical Sciences led this group in conducting a high-resolution characterization of the molecular events that are required for the reprogramming of stem cells. In particular, Nagy and his colleagues were interested in ways to control the path to pluripotency. In this analysis, they discovered an alternative reprogrammed cell, which they called F-class stem cells.

It has been known for many years that when mature, adult cells are reprogrammed into induced pluripotent stem cells (iPSCs) by means forcing expression of key transcription factors (Oct4, Klf4, Sox2, and c-Myc), some cells will stably not express the pluripotency gene Nanog, and fail to acquire full pluripotency, even though these cells look like embryonic stem cells (see Fussner, E. et al. EMBO J. 30, 1778–1789 (2011); Sridharan, R. et al. Cell 136, 364–377 (2009); and Chen, J. et al. Nature Genet. 45, 34–42 (2013)). These partially reprogrammed cells seem to indicate that there are other cell types that can be formed by reprogramming that are not fully pluripotent. Strangely, some labs have reported that treating partially pluripotent cells with vitamin C can reprogram to cells to full pluripotency (Esteban, M. A. et al. Cell Stem Cell 6, 71–79 (2009)).

Nagy and his colleagues used a whole battery of tests to take detailed snapshots of every stage of reprogramming, and in the process, revealed an alternative state of pluripotency. They discovered that high levels of expression of the four reprogramming factors generates cells that do not form typical ESC-like colonies in culture, but are still pluripotent. These are the F-type cells.  F-type cells derived their name from the fuzzy boundaries they form when they grow in culture.

When F-type cells were compared to embryonic-like stem cells, the F-type cells are easier to make, less expensive, and faster to grow. Thus F-class stem cells can be produced more economically in large quantities and this should accelerate drug-screening efforts, disease modeling, and eventually the development of treatments for different illnesses.