Emerging Clinical Technologies - RR

Question 1

What are 5 different types of treatment that can be used for metabolic disorders? Give some examples

Answer 1

1. Diet modification- like the PKU diet; avoid phenylalanine since it can’t be broken down
2. Replacement- give the patient whatever enzyme they are missing/deficient in (give BH4 for BH4 hyperphenylalanemia)
3. Diversion- use an alternate pathway to get rid of the toxic substrate- like in a defect in the urea cycle which causes build up of NH3 so give sodium benzoate which changes NH3 to glycine
4. Inhibition-use an agent that blocks the critical step in a pathway (shut a pathway down)
5. Depletion- remove the substance that is in excess- in hereditary hemochromatosis where get a build up of Fe, just remove the Fe

Question 2

What are some treatments that can be done at the protein level? (2 major categories)

Answer 2

1. Replacement- add the protein back into the patient
2. Enhancement of genetic expression- using one gene to compensate for another, or upregulating the gene that encodes the deficient protein

Question 3

What is the difference between extracellular and intracellular protein replacement therapy? Provide an example

Answer 3

1. Extracellular- adding back the protein that the patient is deficient in
   Example: Hemophilia A- give the patient factor VIII; or with alpha-A1 antitrypsin deficiency give the patient alpha-A1 antitrypsin
2. Intracellular-getting the protein into the cell need to target the specific cell of interest
   Example: Gaucher disease- caused by a deficiency of glucocerebrosidase causing an accumulation of glucocerebrosides. Add the glucocerebrosidase so that it gets picked up by macrophages and brought into lysosomes

Question 4

Even though extracellular protein replacement is easier, there are some problems. What are these problems?

Answer 4

1. Cost- expensive to make these proteins synthetically and use them over a lifetime
2. Patient can have an immune response to the protein
3. Contamination- anytime you process something there’s a risk of contamination

Question 5

What’s an example of a treatment that uses the enhancement of genetic expression?

Answer 5

Sickle cell anemia- treat the mutation in HbS by upregulating the gene that encodes HbF

Question 6

Transplantation can be used for the treatment of what diseases? Why is transplantation a viable treatment?

Answer 6

Hematologic and lysosomal storage disease
Bone marrow transplants work for hematological diseases because they provide the stem cells for all hematological cells
Bone marrow transplants can be used for lysosomal storage diseases since bone marrow makes up 10% of the total cellular mass and therefore contain a high quantity of lysosomes

Question 7

What is the process done during an autologous bone marrow transplant? What are the benefits?

Answer 7

Remove the bone marrow from the patient and isolate the stem cells from the patient. Give the patient chemo and then add the stem cells back into the patient. The benefit is that since this is autologous won’t see any rejection

Question 8

What is the process done during allogenic bone marrow transplants? What is the possible issue?

Answer 8

Remove the bone marrow from the patient. Isolate stem cells from a donor. Give the patient chemo and then add the donors stem cells. Problem is that can get Graft versus host disease where the donor cells attack the patient, and the patient has to be immunosuppressed so that the patient is vulnerable

Question 9

What is the difference between embryonic stem cells and somatic stem cells?

Answer 9

Embryonic stem cells- are pluripotent and can differentiate into any cell type
Somatic stem cells- are self renewing but can only differentiate into cell types that are present in the tissue

Question 10

What are induced pluripotent stem cells (iPS)?

Answer 10

Taking somatic cells and reprogramming them so that they are undifferentiated and can be used as a stem cell

Question 11

What is the process of nuclear transfer?

Answer 11

Take an oocyte and enucleate the cell. Then remove the diploid nucleus from a somatic cell and place back into the enucleated oocyte

Question 12

What is the definition of gene therapy?

Answer 12

the addition of genetic material into human somatic cells for therapeutic/prophylactic/diagnostic purposes

Question 13

What types of diseases can gene therapies be used for?

Answer 13

1. correcting a loss of function mutation by incorporating a functional gene
2. compensating for a deleterious allele by replacing/inactivating this allele

Question 14

What are the requirements for gene therapy?

Answer 14

Need to ID the gene responsible, need to be able to sequence/clone the DNA of interest, need to be able to ID the target tissue, understand how to get the gene to the target tissue, and understand how this gene is transcribed and translated

Question 15

What are the limitations in gene therapy?

Answer 15

Need a vector that can carry the DNA and then deliver this DNA to the target cells

Question 16

What is the issue with using viruses as vectors? What is gene therapy controversial?

Answer 16

Although the virus has lost it’s pathogenic material once it’s inside the body, the virus does what it wants
Controversial: can cause an immune response, may lead to cancer

Question 17

What is antisense therapy used for? How is it used?

Answer 17

Used to downregulate proteins

Add RNAi- this complements mRNA so that the mRNA can’t be translated