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Induced Pluripotent Stem Cells: Enabling Orphan Drug Development

The Orphan Drug Act passed in 1983 to facilitate the development of productions for rare diseases and conditions. It enables the Food and Drug Administration (FDA) to incentivize companies for the development of drugs that might not be “good” business ventures as they treat rare, or orphan, diseases. The incentives of the program are: 1) 7 years of market exclusivity, 2) tax credits up to 50%, 3) exemption from the user fee (part of the regulatory review cost – a whopping $1,405,500 in fiscal year 2010), and 4) possibly an expedited FDA review. There is also an independent Orphan Products Grants Program that provides funding for the clinical develop of such products (1).

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Orphan drug status can be granted for diseases that affect fewer than 200,000 people in one country. Some of these diseases have exotic names such as Jumping Frenchmen of Maine, Kabuki Make-up Syndrome, Split-Hand Deformity, Stiff Person Syndrome, Tangier Disease, and Twin-Twin Transfusion Syndrome, whereas others, are more familiar conditions. While malaria affects more than 500 million people per year worldwide, there are less than 200,000 cases in the U.S.  With such a low prevalence in developed countries such as the U.S., there is little incentive for companies to spend their budget on malaria drugs. In fact, up until 2007, there were no new and improved therapies for malaria in the past 15 years – and the old therapies were not suitable for pregnant women and children. The Orphan Drug act has incentivized companies to do better.

Still, orphan drug development itself faces technical challenges. One of these challenges is the lack of tissue samples to test drugs on. Stem cell research can take orphan drug development to the next level. In particular, induced pluripotent stem cells (iPSCs) have the potential to be disease- and patient-specific cells, enabling the streamlined validation or rejection of treatments. .

One example of the impact stem cell research can have on orphan drug development lies in Niemann-Pick and Gaucher’s disease, two congenital diseases caused by a deficiency in lysosomal enzymes. Lysosomes are involved in degrading waste materials of cells in the body. Without functional enzymes, abnormal metabolic products accumulate in the body. This causes a wide variety of symptoms early in a child’s life. Children with Niemann-Pick get progressive brain damage, and Gaucher disease causes blood disorders, skeletal weakening, and a painfully enlarged liver. By screening already approved FDA compounds on iPSCs, δ-tocopherol and cyclodextrin, and six new classes of compounds have been identified as potential treatment of Niemann-Pick type C and Gaucher’s disease, respectively (2).

In addition to assaying compounds on iPSC lines, scientists can also couple these assays with a method called “high content screening” to understand the mechanism of action of diseases. Identifying the mechanism of action of rare diseases will not only facilitate the development of new therapies, but can also attract more scientists and companies for orphan drug discovery and development (3). In the same vein, using iPSCs to model rare diseases promises to not only resolve the challenge of having means of testing potential orphan therapeutics, but it also promises to streamline validation, making the development of orphan drugs less expensive from a time to return on investment perspective.


[1] United States Food and Drug Administration. (1983). Orphan Drug Act of 1983, Pub. L. no. 97- 414, 21 U.S. Code Section 360, 96 Stat 2049.

[2] Pineda M, Perez-Poyato MS. Current and future therapies for Niemann-Pick C disease. Exp Opin Orphan Drugs. 2013;1:915–923.

[3] Zeng, Xianmin et al. “Concise Review: Modeling Central Nervous System Diseases Using Induced Pluripotent Stem Cells.” Stem Cells Translational Medicine 3.12 (2014): 1418–1428. PMC.


Aradhana Verma has been an SSSCR member since 2011, past-president of the SSSCR- Berkeley chapter, and sits on the SSSCR International Executive Committee. Aradhana is an MD candidate at California Northstate University in Elk Grove, California. She has a Masters in Translational Medicine from UC Berkeley/UC San Francisco and a Bachelor’s in Cognitive Science from UC Berkeley. Her best days begin with a cappuccino and a book by Atul Gawande.  

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