New therapeutic approaches to mendelian disorders.

@article{Dietz2010NewTA,
  title={New therapeutic approaches to mendelian disorders.},
  author={Harry C. Dietz},
  journal={The New England journal of medicine},
  year={2010},
  volume={363 9},
  pages={
          852-63
        }
}
  • H. Dietz
  • Published 25 August 2010
  • Medicine
  • The New England journal of medicine
Thanks to the power of a method to identify etiologic mutations (and hence “causative” genes) in mendelian disease, the molecular mechanisms that give rise to many such diseases are now known. This knowledge has fueled new therapeutic approaches, which are reviewed in this article, the third in the Genomic Medicine series. 
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References

SHOWING 1-10 OF 89 REFERENCES
Randomized, controlled trial of miglustat in Gaucher's disease type 3
To evaluate the efficacy and safety of miglustat, concomitant with enzyme replacement therapy (ERT), in patients with Gaucher's disease type 3 (GD3).
Therapy of Marfan syndrome.
TLDR
TGFbeta antagonists have shown great success in improving or preventing several manifestations of Marfan syndrome in these mice, including aortic aneurysm, and highlight the potential for development of targeted therapies based on discovery of disease genes and interrogation of pathogenesis in murine models.
Treatment of Gaucher disease with an enzyme inhibitor
  • N. Radin
  • Biology, Medicine
    Glycoconjugate Journal
  • 2004
TLDR
The hypothesis is offered predicting that Caucher patients could be treated with a drug that slows the synthesis of glucosylceramide, the lipid that accumulates in this disorder, and 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP), a designer inhibitor that resembles the synthase's substrate and product is found to be effective.
Review of miglustat for clinical management in Gaucher disease type 1
  • C. Ficicioglu
  • Medicine
    Therapeutics and clinical risk management
  • 2008
TLDR
The results of clinical studies and use of miglustat as a therapeutic agent in patients with type I Gaucher disease are discussed.
Translation of the Philadelphia chromosome into therapy for CML.
TLDR
The understanding of resistance to imatinib has rapidly led to strategies to circumvent resistance, which will allow this paradigm of targeting molecular pathogenetic events to be applied to many additional hematologic cancers.
Aminoglycoside-mediated suppression of nonsense mutations in late infantile neuronal ceroid lipofuscinosis.
  • D. Sleat, I. Sohar, R. Gin, P. Lobel
  • Biology, Medicine
    European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society
  • 2001
TLDR
The results suggest that pharmacological suppression of nonsense mutations by aminoglycosides or functionally similar pharmaceuticals may have therapeutic potential in LINCL.
An unexpected twist for autophagy in Crohn's disease
TLDR
Autophagy is important in regulating the secretory function of Paneth cells and the production of inflammatory cytokines in the intestine in mice deficient in the autophagy-related gene product Atg16L1.
Recurrent de novo point mutations in lamin A cause Hutchinson–Gilford progeria syndrome
TLDR
Evidence of mutations in lamin A (LMNA) as the cause of Hutchinson–Gilford progeria syndrome is presented, and the discovery of the molecular basis of this disease may shed light on the general phenomenon of human ageing.
PTC124 targets genetic disorders caused by nonsense mutations
TLDR
The selectivity of PTC124 for premature termination codons, its well characterized activity profile, oral bioavailability and pharmacological properties indicate that this drug may have broad clinical potential for the treatment of a large group of genetic disorders with limited or no therapeutic options.
Gentamicin treatment of Duchenne and Becker muscular dystrophy due to nonsense mutations
TLDR
In the mdx mouse, where muscular dystrophy is due to a nonsense mutation in the dystrophin gene, gentamicin suppressed truncation of the protein and ameliorated the phenotype, and full‐length dyStrophin was not detected in pre‐ and post‐treatment muscle biopsies.
...
1
2
3
4
5
...