When should you genetically test a child?
when there is action to be taken in the present time
What are the challenges to curing single gene mutations?
1) cannot remove, silence, or regulate single genes (en vivo) 2) cannot insert single genes (en vivo)
Urea cycle deficient patients use _____; hypercholesterolemia heterozygotes can receive ____.
sodium benzoate; oral resins
Intracellular proteins are targeted to treat which 2 diseases?
1) Gaucher disease 2) Fabry disease
What is gene therapy?
introduction of DNA or RNA into human cells to treat disease
Dietary restriction is a treatment used in _____ and ______.
Diversion is a treatment strategy for _____ and ____ patients.
urea cycle deficient; hypercholesterolemia
What are 2 approaches to gene therapy?
1) non-viral 2) viral
What is a drawback to cofactor administration?
50% of patients respond
Pts with G6PD deficiency and acute intermittent porphyria should avoid ______ and _______.
antimalarial drugs; barbituates
What are the challenges to curing chromosomal mutations?
1) cannot remove, silence, or regulate extra chromosome material 2) cannot insert missing material
Replacement therapy is an intervention used to treat _____ and _____.
hypothyroidism; bitinidase deficiency
________ and ________ gene therapy approaches can use large insertions.
What is an advantage to adenoviral gene therapy?
wide variety of cell types can be infected; size can be large; stable and easy to get high titers
What is a drawback to replacement of intracellular protein?
Transient expression is a problem in ________ and _______ gene therapy approaches.
Name 4 methods of treating diseases at the level of the mutant protein.
1) cofactor administration 2) replace extracellular protein 3) replace intracellular protein 4) target intracellular protein
What disease do farnesyl transferase inhibitors treat?
What do viral approaches to gene therapy use?
1) oncoretrovirues 2) lentiviruses 3) AAVs
Inhibition is used to treat pts with ______.
Which approaches to gene therapy are short lived?
adenoviral and non-viral
What drugs are used to inhibit hypercholesterolemia?
__________ is used to deplete cholesterol in hypercholesterolemia patients.
Name 3 broad types of DNA mutations.
1) chromosomal 2) single gene 3) complex
What are the challenges to curing complex gene mutations?
1) cannot remove, silence, or regulate multiple genes 2) cannot insert multiple genes 3) gene-environment interactions not fully understood
What does G6PD stand for?
What is an example of an indirect therapy for a metabolic disorder?
treatment of PKU with diet
PKU and galactosemia should avoid ingesting _____ and _____, respectively.
Intracellular protein replacement therapy is used to treat what disease?
Name 2 examples of diseases treated with cofactor administration.
1) pyridoxine-responsive homocyctinuria 2) biotinidase deficiency
Depletion is a technique used to treat ________.
Genetic _____ are rare, but many genetic diseases can be ______ on some level.
_____ is the replacement enzyme in hypothyroidism; _____ is replaced in biotinidase deficient pts.
What 3 treatment strategies can be used to treat hypercholesterolemia?
1) diversion 2) inhibition 3) depletion
Which is the safest approach to gene therapy and why?
non-viral b/c it doesn't integrate into the genome
What is a disadvantage to non-viral gene therapy?
low efficiency; transient expression
What's the idea behind gene therapy?
introduction of a gene and its product should cure or slow down disease progression
Avoidance is an intervention used to treat ____ and ____.
G6PD; acute intermittent porphyria
What is LDL apheresis?
similar to dialysis, it is a treatment used to eliminate LDL from the bloodstream
What is an advantage to non-viral gene therapy?
insert size can be very large; can deliver mini-chromosomes; minimal host immune response
What is a disadvantage to retroviral gene therapy?
small insert size; can only infect dividing cells
What is a disadvantage to adenoviral gene therapy?
doesn't integrate into genome; transient expression; risk of malignant transformation
What is an advantage to retroviral gene therapy?
it integrates into the cell genome w/ minimal host immune reactions
Name 2 examples of replacement extracellular proteins.
1) factor VIII in hemophilia 2) alpha-1-antitrypsin
What do non-viral approaches to gene therapy use?
1) naked DNA 2) liposomes