Article

Drug development for orphan diseases in the context of personalized medicine.

Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Mich. 48109-0534, USA.
Translational research : the journal of laboratory and clinical medicine 12/2009; 154(6):314-22. DOI: 10.1016/j.trsl.2009.03.008
Source: PubMed

ABSTRACT Orphan diseases are diseases that are found in less than 200,000 patients in the United States, which is the cutoff point for the number of patients for a drug to be profitable. Because many thousands of orphan diseases exist in the aggregate (about 20 to 30 million Americans have orphan diseases), these patients are disenfranchised from drug development by the pharmaceutical industry. Orphan drugs are a large part of personalized medicine. The orphan diseases are often so rare that a physician may observe only 1 case a year or less. So proper treatment is a personalized encounter between doctor and patient. Academic physician-scientists have tried to fill this therapy vacuum by working on developing orphan drugs. But many disincentives are involved, which include career disincentives, lack of funding, and the multiple areas of expertise that are required. Positive developments include formation of the National Organization for Rare Diseases, the Orphan Drug Act, the development of a grant program to fund orphan drug development, the formation of the National Institutes of Health Office of Rare Diseases, and the passage of orphan drug legislation by other countries. Progress has increased, but the 300 orphan drugs and devices approved in the last 25 years are still only a drop in the bucket compared with the many thousands of orphan diseases. I believe we must do better. I present my own 2 examples of the positive and the negative aspects of orphan drug development, and I end this article by giving recommendations on how we might succeed both in developing more orphan drugs and in rescuing the pharmaceutical industry from its impending economic collapse.

0 Followers
 · 
105 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: A layer-by-layer self-assembly method leads to the formation of Au@ZnMoS4 core–shell nanoparticles (NPs). The PEGylated Au@ZnMoS4 NPs are highly water-dispersible, exhibit no cytotoxicity, and can penetrate the cell membrane to selectively remove copper(I) ions from HepG2 cells in the presence of other endogenous and biologically essential metal ions, including Mg2+, Ca2+, Mn2+, and Fe2+, demonstrating their potential as a novel intracellular copper detoxifying agent.
    Chemistry of Materials 11/2013; 25(23):4703–4709. DOI:10.1021/cm402147u · 8.54 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Introduction: Pseudoxanthoma elasticum (PXE), a multisystem orphan disease, clinically affects the skin, the eyes and the cardiovascular system with considerable morbidity and mortality. The clinical manifestations reflect the underlying pathology consisting of ectopic mineralization of peripheral connective tissues. Areas covered: The diagnostic criteria of PXE include characteristic clinical findings, together with histopathology of accumulation of pleiomorphic elastic structures in the dermis with progressive mineralization, and the presence of mutations in the ABCC6 gene. PXE-like cutaneous changes can also be encountered in other ectopic mineralization disorders, including generalized arterial calcification of infancy (GACI) caused by mutations in the ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) gene. In some cases, overlapping clinical features of PXE/GACI, associated with mutations either in ABCC6 or ENPP1, have been noted. PXE demonstrates considerable inter- and intrafamilial heterogeneity, and consequently, accurate diagnosis is required for appropriate classification with prognostic implications. There is no effective and specific treatment for the systemic manifestations of PXE, but effective therapies to counteract the ocular complications are in current clinical use. Expert opinion: A number of observations in the animal model, the Abcc6-/-, mouse, have indicated that the mineral composition of diet, particularly the magnesium content, can influence the severity of the mineralization phenotype. These observations suggest that appropriate dietary interventions, coupled with lifestyle modifications, including smoking cessation, might alleviate the symptoms and improve the quality of life of individuals affected with this, currently intractable, orphan disease.
    06/2014; 2(6). DOI:10.1517/21678707.2014.908702
  • [Show abstract] [Hide abstract]
    ABSTRACT: Rare diseases are of increasing concern to private and public healthcare insurance plans. Largely neglected by manufacturers before the 1983 passing of the Orphan Drug Act (ODA), orphan drugs have become a commercialization target of steadily increasing importance to the healthcare industry. The ODA mandates the coverage of rare diseases, which are defined in research communities as diseases that are so infrequent that there is no reasonable expectation of a drugmaker recovering the cost of developing that drug.
    American Health and Drug Benefits 11/2013; 6(9):589-98.