Year: 2026
Type: article
Abstract: e 21 st century has ushered in a revolution in Mendelian disorders.Sequencing of the whole human genome and the advent of high-throughput sequencing technologies have identified genetic etiologies for more than 6,000 genetic disorders.With exome sequencing becoming the first-tier test for possible genetic phenotypes, etiological diagnosis has become easier and is being done by clinicians with and without medical genetics training.e long-awaited gene therapy successes are also among the major highlights of this century.Other than gene therapy, drug therapies based on an understanding of the pathogenesis of the disorders have shown early successes.Enzyme replacement therapies for lysosomal storage disorders, pathway-based treatments for RASopathies, and small interfering RNA-based therapies for acute intermittent porphyria, hypercholesterolemia, primary hyperoxaluria type 1 and hereditary transthyretinmediated amyloidosis are some examples.e drug vosoritide, developed for achondroplasia, is an example of targeting molecular pathology.It has been more than a decade since animal studies showed proof of concept about the effect of vosoritide on the growth plates, and more than 5 years since the first report of its efficacy and safety in children was published.Achondroplasia is the commonest skeletal dysplasia, and its characteristic phenotype makes clinical diagnosis easy.It occurs due to a gain-of-function mutation in the FGFR3 gene.Mutations at position 1138 of the gene are present in all patients of achondroplasia from India, with 1138G>A in 94.7% and the rare 1138 G>C substitution in 5.3%.[1] e C-type natriuretic peptide downregulates aberrant FGFR3 signaling in chondrocytes by inhibiting the mitogen activated protein kinase-extracellular signal regulated kinase (MAPK-ERK) pathway.Vosoritide is a recombinant analog of the C-type natriuretic peptide that has been engineered to resist degradation and increase its half-life.Based on this evidence, vosoritide has been approved for use in children with achondroplasia and open epiphyses from birth in the USA, Japan, and Australia, and from age ≥4 months in the European Union.[2] It is interesting to know that the DNA variations in NPR2 gene, which codes for natriuretic peptide receptor B (which binds the extracellular ligand, C-type natriuretic peptide), cause another skeletal dysplasia, namely acromesomelic dysplasia.e mechanism of action of vosoritide is targeted to the pathogenetic gain-of-function FGFR3 mutation causing achondroplasia, and scientifically appears to be a very effective way of treating the disorder.is brought a wave of positivity and great hope among patients with achondroplasia, especially children and their families.e most important problem in achondroplasia is markedly short stature, with an average adult height of around 130 cm.Before vosoritide, the available treatments for short stature in achondroplasia, such as growth hormone (GH) therapy and limb lengthening surgeries, provided limited benefit, with the latter being too invasive and prolonged.Early studies of vosoritide established the safety profile and documented an increase in growth https://ispae-jped.com
Author: Shubha R. Phadke
Institution: Bharati Vidyapeeth (Deemed to be University)
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
OpenAlex ID: W7123638109