Treatment of Genetic Disease

Question 1

When should you genetically test a child?

Answer 1

when there is action to be taken in the present time

Question 2

What are the challenges to curing single gene mutations?

Answer 2

1) cannot remove, silence, or regulate single genes (en vivo) 2) cannot insert single genes (en vivo)

Question 2

Urea cycle deficient patients use _____; hypercholesterolemia heterozygotes can receive ____.

Answer 2

sodium benzoate; oral resins

Question 2

Intracellular proteins are targeted to treat which 2 diseases?

Answer 2

1) Gaucher disease 2) Fabry disease

Question 3

What is gene therapy?

Answer 3

introduction of DNA or RNA into human cells to treat disease

Question 4

Dietary restriction is a treatment used in _____ and ______.

Answer 4

PKU; galactosemia

Question 5

Diversion is a treatment strategy for _____ and ____ patients.

Answer 5

urea cycle deficient; hypercholesterolemia

Question 5

What are 2 approaches to gene therapy?

Answer 5

1) non-viral 2) viral

Question 6

What is a drawback to cofactor administration?

Answer 6

50% of patients respond

Question 7

Pts with G6PD deficiency and acute intermittent porphyria should avoid ______ and _______.

Answer 7

antimalarial drugs; barbituates

Question 8

What are the challenges to curing chromosomal mutations?

Answer 8

1) cannot remove, silence, or regulate extra chromosome material 2) cannot insert missing material

Question 8

Replacement therapy is an intervention used to treat _____ and _____.

Answer 8

hypothyroidism; bitinidase deficiency

Question 9

________ and ________ gene therapy approaches can use large insertions.

Answer 9

Adenoviral; non-viral

Question 10

What is an advantage to adenoviral gene therapy?

Answer 10

wide variety of cell types can be infected; size can be large; stable and easy to get high titers

Question 11

What is a drawback to replacement of intracellular protein?

Answer 11

cost

Question 12

Transient expression is a problem in ________ and _______ gene therapy approaches.

Answer 12

adenoviral; non-viral

Question 13

Name 4 methods of treating diseases at the level of the mutant protein.

Answer 13

1) cofactor administration 2) replace extracellular protein 3) replace intracellular protein 4) target intracellular protein

Question 13

What disease do farnesyl transferase inhibitors treat?

Answer 13

Progeria

Question 13

What do viral approaches to gene therapy use?

Answer 13

1) oncoretrovirues 2) lentiviruses 3) AAVs

Question 14

Inhibition is used to treat pts with ______.

Answer 14

hypercholesterolemia

Question 15

Which approaches to gene therapy are short lived?

Answer 15

adenoviral and non-viral

Question 17

What drugs are used to inhibit hypercholesterolemia?

Answer 17

statins

Question 17

__________ is used to deplete cholesterol in hypercholesterolemia patients.

Answer 17

LDL apheresis

Question 19

Name 3 broad types of DNA mutations.

Answer 19

1) chromosomal 2) single gene 3) complex

Question 21

What are the challenges to curing complex gene mutations?

Answer 21

1) cannot remove, silence, or regulate multiple genes 2) cannot insert multiple genes 3) gene-environment interactions not fully understood

Question 21

What does G6PD stand for?

Answer 21

glucose-6-phosphate dehydrogenase

Question 22

What is an example of an indirect therapy for a metabolic disorder?

Answer 22

treatment of PKU with diet

Question 23

PKU and galactosemia should avoid ingesting _____ and _____, respectively.

Answer 23

phenylalanine; galactose

Question 24

Intracellular protein replacement therapy is used to treat what disease?

Answer 24

ADA deficiency

Question 26

Name 2 examples of diseases treated with cofactor administration.

Answer 26

1) pyridoxine-responsive homocyctinuria 2) biotinidase deficiency

Question 28

Depletion is a technique used to treat ________.

Answer 28

hypercholesterolemia

Question 30

Genetic _____ are rare, but many genetic diseases can be ______ on some level.

Answer 30

cures; managed

Question 32

_____ is the replacement enzyme in hypothyroidism; _____ is replaced in biotinidase deficient pts.

Answer 32

Thyroxine; biotin

Question 33

What 3 treatment strategies can be used to treat hypercholesterolemia?

Answer 33

1) diversion 2) inhibition 3) depletion

Question 34

Which is the safest approach to gene therapy and why?

Answer 34

non-viral b/c it doesn’t integrate into the genome

Question 35

What is a disadvantage to non-viral gene therapy?

Answer 35

low efficiency; transient expression

Question 36

What’s the idea behind gene therapy?

Answer 36

introduction of a gene and its product should cure or slow down disease progression

Question 37

Avoidance is an intervention used to treat ____ and ____.

Answer 37

G6PD; acute intermittent porphyria

Question 40

What is LDL apheresis?

Answer 40

similar to dialysis, it is a treatment used to eliminate LDL from the bloodstream

Question 40

What is an advantage to non-viral gene therapy?

Answer 40

insert size can be very large; can deliver mini-chromosomes; minimal host immune response

Question 41

What is a disadvantage to retroviral gene therapy?

Answer 41

small insert size; can only infect dividing cells

Question 42

What is a disadvantage to adenoviral gene therapy?

Answer 42

doesn’t integrate into genome; transient expression; risk of malignant transformation

Question 43

What is an advantage to retroviral gene therapy?

Answer 43

it integrates into the cell genome w/ minimal host immune reactions

Question 44

Name 2 examples of replacement extracellular proteins.

Answer 44

1) factor VIII in hemophilia 2) alpha-1-antitrypsin

Question 45

What do non-viral approaches to gene therapy use?

Answer 45

1) naked DNA 2) liposomes