Table II.

Selected rare genetic diseases and their pathophysiology and therapeutics

Disease name	Pathophysiology	Current Therapeutics	Investigational Therapeutics	References
Angelman syndrome	Deletion of chromosome 15	Clonazepam	Stem cell, small molecules (SM)*	[Grant 2000]; [Chamberlain et al., 2010]
Cystic fibrosis	Mutations of CFTR†	Lumacaftor/ivacaftor	Gene therapy, SM	[Griesenbach et al., 2004; Van Goor et al., 2011]
Retinal degeneration	Mutations of photoreceptors	Fenretinide	Gene therapy, stem cell, SM	[Kaewkhaw et al., 2016; Trifunovic et al., 2012]
Amyotrophic lateral sclerosis	Death of motor neurons	Riluzole	Stem cell, SM	[Bensimon et al., 1994; DeLoach et al., 2015]
Sickle cell disease	Substitution of hemoglobin	Hydroxyurea	Gene therapy, SM	[Charache et al., 1995; Hoban et al., 2016; Telen 2016]
Osteogenesis imperfecta	Substitution of glycine in collagen	Bisphosphonates	Growth hormone, gene therapy	[Evans 2012; Glorieux et al., 1998]
Hutchinson-Gilford progeria	Mutation of lamin A (LMNA)	Farnesyltransferase inhibitors	SM, Antisense oligonucleotide	[Lo Cicero and Nissan 2015; Moorthy et al., 2013]
Huntington disease	Mutation of Huntingtin gene (HTT)	Tetrabenazine	Stem cell, gene therapy, SM	[Chen et al., 2014; McLellan et al., 1974]

Note:

^*SM – Small molecules.

^†CFTR – as cystic fibrosis transmembrane conductance regulator. All the above diseases have no cure, except that a small population of sickle cell patients can be cured by bone marrow transplantation. Current therapeutics may reduce symptoms or delay disease progression. Note that no gene therapy product has yet been approved by the US FDA.