Treatment of Genetic Disease

Question 1

Whis is counseling and prenatal/carrier testing important?

Answer 1

provide information and allow for planning and education

Question 2

Drug therapy treats

Answer 2

the symptoms

Question 3

What are the two major surgical interventions?

Answer 3

transplantation and repair

Question 4

How are metabolic disorders usually treated?

Answer 4

• dietary modification or restriction

- replacement of missing metabolite

Question 5

Examples of metabolic treatmetn

Answer 5

• PKU diet

- supplementing diet with BH4

Question 6

What is diversion?

Answer 6

use of other metabolic pathways to prevent accumulation of a metabolite
-redirect to break down substances to harmless compounds

Question 7

Give an example of Diversion

Answer 7

urea cycle defect leads to build up of NH3 that can’t be fully corrected by diet–>sodium benxoate pushes excess NH3 to combine with glycine–>hippurate–>excreted in urine

Question 8

Whay is inhibition?

Answer 8

modifying the rate of synthesis by using a drug or other agen that slows or blocks a critical step in the pathway

Question 9

What is depletion?

Answer 9

removal of a substance that is in excess

Question 10

Give an example of depletion

Answer 10

Hereditary hemochromatosis –accumulation of iron controlled by regular phlebotomy

Question 11

How would treat at the protein level? Give examples

Answer 11

replacement of missing proteins:
-Hemophilia A–>factor 8
alpha1 antitrypsin defiency–>shots of the protein

Question 12

What are the problems with treating at the protein level?

Answer 12

cost, availability, antibody production in the patient, contamination

Question 13

Replacement intracellularuly one must

Answer 13

target the therapy, which is much more difficult to do.

Question 14

Enhancing genetic expression includes

Answer 14

use of one gene to compensate for the mutation in another

Question 15

What is an example of enhanced genetic expression?

Answer 15

Enhancing the expression of HbF to provide an alternative to the HbS

Question 16

How does bone marrow transplant work?

Answer 16

• remove the disease clone and replace it with unaffected cells
• collect bone marrow stem cells from the patient or a matched donor
• trnasplanted cells will reestablish in the new host and hopefully cure the disease

Question 17

What is a drawback to bone marrow transplant?

Answer 17

sometimes not all disease cells will be removed and the disease could be reestablished

Question 18

Why has bone marrow transplant shown to be useful in lysosomal storage disease?

Answer 18

10% of the body’s cell mass and extracellular transfer from the normal marrow may stimulate function in other cells
-acts a a source of monocytes

Question 19

Why should bone marrow transplant be used early in life?

Answer 19

If done early, will limit the negative neuro impact of the disease

Question 20

What are stem cells?

Answer 20

Self-renewing, undifferentiated cells

-can proliferate and produce a wide variety

Question 21

What are the two major calasses of stem cells?

Answer 21

Embryonic: pluripotent

Somatic: limited to the tissue of origin

Question 22

Embryonic stem cells are a poteintial therapy for

Answer 22

Parkinson’s disease and AD

Question 23

Embyronic stem cells are a potential source of cells for

Answer 23

tissue grafting and organ transplants

Question 24

What is the problem with embryonic stem cell use?

Answer 24

Ethical dilemma

Question 25

What are the problems with allogenic stem cell use?

Answer 25

immunosuppression

-graft vs host disease

Question 26

What are induced pluripotent stem cells?

Answer 26

cells collected from an individual are treated with reprogramming factros that have been shown to reverse the differentiation in the cells and revert them to a state of pluripotency

• fx like embryonic stem cells
• no immune response because they are from the donor

Question 27

Cloning is best described as

Answer 27

nuclear transfer

Question 28

The potential ill effects of cloning;

potential benefits of cloning

Answer 28

possible negative impact on genes, chromosomes, normal cellular processes such as aging
-potential benefits for agriculture-improving crops, herds, etc

Question 29

In addition to the rapid shortening of telomeres dolly also had

Answer 29

inappropriate imprinting

Question 30

What is gene therapy?

Answer 30

deliberate introduction of genetic material into human somatic cells for therapeuatic, prophylactic or diagnostic purposes

Question 31

What are the classes of gene therapy?

Answer 31

incorporating a -functional gene into the genome

• compensation for a deleterious dominant allele by replacing or inactivating the mutant allele
• adding genetic material the has a pharma effect

Question 32

What are the requirements for gene therapy?

Answer 32

• identification of gene
• availability of gene sequence or cloned DNA from the gene of interest
• Identification of target tissue
• ability to deliver gene to target
• understanding of gene biochemistry
• understanding of expression

Question 33

What is the major limitation of gene therapy?

Answer 33

Delivery of gene to target
-vector must be able to carry the DNA
-must be able to insert DNA into the target cell
-

Question 34

liposomes are interesting

Answer 34

vectors

Question 35

Gene therapy using liposomes is a

Answer 35

temporary fix as DNA is degraded or lost when the cell dies

Question 36

What is the difference between in vivo and ex vivo therapy?

Answer 36

in vivo: genes are incorporated into vectors and targeted to a specific cells in the body

ex vivo: extracted from patient, modified, and returned to the patient

Question 37

How has the history with gene therapy been?

Answer 37

Successful with ADA deficiency, then banned for a while because of deaths. Have been some more recent successes

Question 38

What is antisens DNA therapy?

Answer 38

• downregulates protein production
• cancer characterized by overproduction of a protein
• incoporate an antisense strand into the cells to block translation

Question 39

What is RNA interference?

Answer 39

 Targeted degradation of
mRNA
 Destroy mRNA from negative dominant mutations while leaving the second allele alone.
 Reduce the concentration of an mRNA that is over expressed

Question 40

What is AAV?

Answer 40

on-pathogenic vector
http://www.virology.wisc.edu/virusworld/PS10/aav _Adeno-Associated_virus_vmd.jpg
 Reduces the likelihood of an immune reaction
 Is found in many serotypes – so the proper vector can be matched to a particular cell type
 Non-integrative, so will not disrupt cancer genes.