Stem cells approved to treat 'orphan' disease

Dan Vergano, USA Today, May 3, 2010

Stargardt's Macular Dystrophy is the most common form of genetic juvenile macular degeneration. Manifestation of the condition begins in late childhood, leading to legal blindness. It is symptomatically similar to age-related macular degeneration, and it affects approximately one in 10,000 children.  Olympic and Paralympic skier Brian McKeever is the best-known victim of the disease, which has no treatment.  Today the company Advanced Cell Technology obtained "Orphan Drug Status" of use of its embryonic stem cell derived product MA09-hRPE as a treatment for Stargardt's disease. 

Orphan Drug Status is a mechanism the government uses to promote interest of pharmaceutical in disease for which a small market exists.  Typically to obtain this the target market must be less than 200,000 people in the United States.  Orphan Drug Status allows a company to retain market exclusivity for seven years, as well as allows for various clinical trial tax incentives.

Human embryonic stem cells have been demonstrated to be capable of giving rise to the cells that make up practically every tissue in the body.  The ability of these cells to make anything from liver, to lung, to nerve cells makes them attractive as sources of replacement tissues to biomedical researchers. Last year the Obama Administration opened federal funding to more-recent generations of such stem cells, and in January allowed research funding to cells such as ACT's, grown from a single cell clipped from an early-stage embryo.

Designation of Orphan Drug Status is not approval of the embryonic stem cell based product for sale, but only classifies the cells as a product in development.  Approval of a drug, whether it is a chemical, a biologic, or a cell, requires clinical trials in which safety and efficacy is demonstrated.  The initial hurdle companies must pass is to obtain Investigational New Drug status.  This was only granted to one embryonic stem cell company, Geron, for use of their embryonic stem cell derived oligodendrocytes for treatment of spinal cord injury.  The approval, however, was rapidly retracted after additional preclinical data demonstrated development of abnormal growths in treated animals.  Subsequent to IND approval companies have to demonstrate safety in Phase I studies, efficacy in Phase II studies, and double blinded efficacy in Phase III studies which usually involve numerous clinical trial sites. 

The major problem with embryonic stem cell derived products is the risk of tumor formation.  In general embryonic stem cells are defined by the ability to form a type of cancer called teratoma.  These tumors are highly aggressive and comprise numerous cells of the body.  When Advanced Cell Technologies or Geron are differentiating retinal epithelia cells, or oligodendrocytes, respective, they must demonstrate to the FDA that no contaminating stem cells are present in the injection mixture that could possibly lead to tumor formation.  Another drawback of embryonic stem cell technology is that it is extremely difficult to selectively add new cells to the area of injury.  Specifically, the de novo created functional body cells must be capable of integrating into the existing cells and taking over their function.  Optimization of these approaches requires understand the molecular cues involved in natural stem cell differentiation into cells of the body.    Yet another drawback is that embryonic stem cell lines are not patient-specific.  This requires the use of immune suppression, which often comes with numerous side effects.