Treatments of Genetic Disease

Question 1

What are some preliminary tests for genetic diseases?

Answer 1

Counseling; prenatal/carrier testing; drug therapy (usually treats symptoms) and surgery (transplants, repairs, etc.)

Question 2

What is an example of trying to treat a metabolic disorder? What are consequences of treating it?

Answer 2

PKU (Phe buildup); it’s life-long and requires diet restrictions, and it can be difficult to ask family to participate in the diet

Question 3

What is adding back something that is missing? What is an example?

Answer 3

Replacement; BH4 hyperphenyalanemia

Question 4

What is the concept of diversion?

Answer 4

Use other pathways to avoid accumulation of a metabolite; redirect to breakdown substances to harmless compounds (NH3 and glycine combined to form hippurate)

Question 5

What are two other ways to treat metabolic disorders (Fe)?

Answer 5

Modify the rate of synthesis by using a drug or agent to slow a critical step in pathway; remove excess substance (e.g. hereditary hemochromatosis via phlebotomoy, or removal of blood)

Question 6

What about treatment at the protein level? What are associated problems?

Answer 6

Replacement (EC) like using Factor VIII or alpha1-antitrypsin;
cost, availability, Ab production in patient against replacement, contamination

Question 7

What must happen with intracellular replacement at the protein level? What is an example? How is it treated?

Answer 7

Target specific cell type;
Gaucher disease: lysosomal storage disease due to glucocerebrosidase deficiency, where treatment is macrophage picking up a modified glucosidase so that enzyme can cross lysosomal membrane

Question 8

In the case of sickle cell anemia, what can be done to compensate for mutation?

Answer 8

Use another gene; use decitabine, which can lead to hypomethylated DNA by inhibiting methyltransferase and you can have more HbF and less deoxyHb S

Question 9

What are the steps in bone marrow transplantation?

Answer 9

1. Remove disease clone
2. Replace unaffected cells
3. Collect bone marrow stem cells from patient or matched donor
4. Transplanted cell establish in new host to hopefully cure disease (must get rid of diseased cells)

Question 10

To deal with lysosomal storage diseases, what does EC bone marrow transfer help do?

Answer 10

Stim function of other cells;

source of mononuclear phagocytes to help reduce organ size; also limits neg neurological impact of disease

Question 11

What are embryonic stem cells? somatic?

Answer 11

Pluripotent and can differentiate to any cell type; self-renewing but can only differentiate into cell types present in tissue of origin

Question 12

What are ESC’s potential therapy for? Source of cells for? What is the downside?

Answer 12

Parkinson’s; Alzheimer’s;
tissue grafting, organ transplants;
The source of the cells are embryos, which leads to ethical concerns

Question 13

If someone requires allogeneic transplantation, what is a possible negative consequence?

Answer 13

Immunosuppression; graft vs. host disease (presence of foreign cells)

Question 14

What is the idea of induced pluripotent stem cells?

Answer 14

Take adult cells, treat using reprogramming factors, revert them to state of pluripotency such that they can re-differentiate and be transplanted into patient again

Question 15

What is the idea behind cloning? What is a consequence? What happens in humans?

Answer 15

Single donor cell and unfertilized egg from two individuals, with latter enucleated and nucleus from former injected into latter, and implant into surrogate mother; negative impact on genes, chromosomes;
take two eggs, transfer nucleus of one (patient) to the other (donor) and use IVF or ICSI to fertilize egg

Question 16

What is a problem of cloning in terms of duplication?

Answer 16

Not an exact duplicate based on environmental factors like size differences or personality!!

Question 17

Given a mutation, what is the goal of gene therapy now?

Answer 17

Instead of repairing the gene, incorporate a normal gene somewhere in the genome to compensate for the mutation

Question 18

What are three classes of gene therapy?

Answer 18

1. incorporate functional gene into genome with loss of function mutation
2. replace/inactivate mutant allele
3. Genetic material with pharmcological effect

Question 19

What are the requirements for successful gene therapy?

Answer 19

1. ID gene
2. Gene sequence or cloned DNA from gene of interest must be there
3. ID target tissue
4. Deliver gene to target
5. Understand gene biochem
6. Understand gene expression

Question 20

What is the major limitation of gene therapy?

Answer 20

Delivery of gene to target: use vector that has to insert DNA into target cell

Question 21

What would make DNA therapy most permanent? What can be used for temporary incorporation in cytoplasm?

Answer 21

Incorporated into host cell’s DNA;

liposome that carries DNA of interest

Question 22

Compare in vivo vs. ex vivo therapy

Answer 22

In vivo: genes incorporated into vectors and target to cells in the body
Ex vivo: cells extracted, modded, and returned to patient

Question 23

What is compromised in ADA deficiency? What is the consequence? What was therapy for this?

Answer 23

Adenosine deaminase; buildup of dATP leading to lymphocyte death;
T-cells collected, grown in vitro, stimulated to proliferate, use retroviral vectors carrying non- mutant ADA cDNA, reinfused into patients

Question 24

Who should be subject to gene therapy?

Answer 24

Patients failing conventional therapies with less than 3 months to live put onto new protocols

Question 25

What is an alternative to somatic cell gene therapy? Why is it controversial?

Answer 25

Germ line gene therapy, which could lead to manipulating genes that create individual with desired characteristics (evolution tampering?