Table 4.

Therapeutic modalities currently available for rare genetic diseases

Treatment modality	Principle	Conditions for which there is clinical approval	Reference
Substrate reduction therapy	Inhibiting the biosynthesis of Storage metabolites in the lysosomes by using small molecules.	Gaucher disease, Fabry disease, Niemann-Pick type C, MPS-IIIB	[124]
Enzyme replacement therapy	Recombinant enzymes that are modified to provide a longer half-life, more potent activity, resistance to degradation or targeting to a specific organ, tissue or cell type	Gaucher disease, Fabry disease, MPS I, MPS II, Pompe disease, MPS VI, Wolman disease, Batten disease, MPS IVA, MPS VII and α-mannosidosis	[125]
Oligonucleotide therapies	Targeting RNA to reduce the production of a specific disease-associated protein by promoting degradation of its mRNA.	SMA and DMD (Nusinersen, Eteplirsen)	[126]
Gene therapy	A vector is used to express a transgene (with the endogenous sequence or codon optimized) that encodes the desired protein, under the control of an appropriate promoter	SMA, hemophilia A, hemophilia B, adrenoleukodystrophy, β-thalassemia, sickle cell disease	[127]
Hematopoietic stem cell therapy	The ability of the transplanted cells and/or their progeny to contribute to fixed-tissue macrophage populations in the affected tissues and to become local permanent sources of functional lysosomal enzymes.	MPS I, MPS II, metachromatic leukodystrophy, Krabbe, β-thalassemia, sickle cell disease, Gaucher disease, MPS IVA, epidermolysis bullosa	[128]
Iron chelation therapy	To maintain safe levels of body iron at all times, by balancing iron intake from blood transfusion with iron excretion by chelation	β-thalassemia	[129]