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Flashcards in Treatment of Genetic Disorders Deck (11)
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describe an example of coenzyme supplementation

  • increasing vit. B6/PLP in patients with homocystinuria to increase the activity of the mutant cystathione B-synthase


describe PKU I vs PKU II and treatment for PKU-I

  • PKU I = Phe hydroxylase deficiency
    • dietary restriction of Phe and supplementation w/ tyrosine
    • pharmacological doses of BH4 (sapropterin) 
  • PKU II: lack of BH4/BH2
    • prognosis much worse since BH4 needed in brain for catecholamine synthesis


describe treatment in urea cycle disorders

  • metabolite diversion
    • ammonia cannot be removed by the urea cycle because of a genetic defect in urea cycle enzymes
    • the administration of sodium benzoate diverts ammonia to glycine synthesis which is eventually excreted as hippurate


describe a solution of protein stability in protein replacement therapies

  • polyethylene glycol derivatization (PEGylation): carbohydrate moiety is added to protein to shield it but does not interfere with enzyme active site
    • may protect protein from rapid degradation
    • may reduce clearance by kidney
    • may reduce immune response


describe a treatment of AR-SCID (ADA deficiency)

  • bone marrow transplant
  • protein replacement therapy
    • PEG-ADA was found to be better than unmodified ADA in restoring immune function
  • gene therapy


explain how Gaucer disease may be treated with enzyme replacement therapy 

  • PEGylation of recombinant B-glucocosidase (aka B-glucocerebrosidase) protein 
    • may be targeted to macrophage lysosomes
    • exposure of mannose residues allows lysosomal uptake


name 2 examples therapeutic targeting of signal transduction pathways in cancer cells

  • tyrosine kinase inhibitor: imatinib aka Gleevac
  • HER2 antibodies: Herceptin used in Her2+ breast cancer


explain epigenetic modification used in sickle cell disease

  • switching on fetal globin synthesis by using hydroxyurea by inhibiting histone deacetylation 


describe how adenoviruses work

  • adenovirus contains the engineered functional gene that is then injected into the cell
    • the gene is then extra-chromosomal (NOT part of cell's genome)


explain 2 problems with gene therapy

  1. immune response
  2. tumor formation
    • insertional mutagenesis induces a tumor if the DNA is integrated in the wrong place in the genome
      • may destroy a tumor suppressor gene
      • may activate a protooncogene


describe Gendicine

  • Gendicine uses an adenovirus as a vector for p53
    • virus is injected directly into the tumor, reinstating endogenous production of p53