Genetics Exam Iii: Current/future Therapeutic Approaches

Front 1

The use or alteration of cells for therapeutic outcome

Back 1

Biotechnology

Front 2

Manipulation of the genetic material of cells

-suppressing or enhancing gene activity
-moving genetic material from one species to another

Back 2

Genetic engineering

Front 3

Applications of recombinant DNA technology

Back 3

1. Recombinant Insulin
2. Recombinant erthropoietin (Epo): increase RBC count
3. Recombinant thrombopoietin: increase platelet count
4. Recombinant granulocyte colony stimulating factor: increase WBC.

Front 4

How are Recombinant erythropoietin, thrombopoietin, and granulocyte colony stimulating factor handy for cancer patients?

Back 4

Patients that are undergoing radiation treatments, which kills stem cells. These recombinant products can bring these cell count back to normal.

Front 5

What disease is a myopathy caused by mutations in the alpha glucosidase (GAA) gene?

Back 5

Pompe disease

Front 6

What inheritance pattern is Pompe's disease?

Back 6

Recessive disorder

Front 7

What are the characterisitcs of Pompe disease?

Back 7

1. Muscle weakness (hypotonia)
2. Cardiomegaly

Front 8

Why does the heart get so big in Pompe disease?

Back 8

Patients have a mutation in a lysosomal enzyme gene which breaks down glycogen.

So glycogen goes into muscles, but does not get cleared-out. The excess glycogen causes the heart to get very large.

Front 9

Lysosomal targeting and extgra-cellular secretion of lysosomal enzymes

Back 9

Protein of GAA comes in 2 forms: catalytic & signaling. Receptors seize signaling-GAA and drag it into the lysosome. Protein is then cleaved into a mature form. Some protein is secreted out of the cell.

Front 10

Cross correction

Back 10

Studies showed that if you had another cell w/o a deficiency, the receptors in the abnormal cell would migrate to the membrane and drag the secreted proteins from the other cell into it's own lysosome.

Front 11

CHO Chinese hamster ovary cell

Back 11

Genetically engineered into a manufacturing cell forced to overproduce proteins.

Front 12

Genetically engineered GAA = Myozyme

Back 12

Reduced cardiomegaly and muscle biopsy showed dramatic improvement in glycogen breakdown.

Front 13

Other lysosomal drugs that are produced in the same way Myozyme is?

Back 13

1. Fabrazyme: Fabry disease, abnormal storage of a substance primarily in kidney and heart cells.

2. Cerezyme: Gaucher disease, affects bone marrow and spleen, deficiency of glucocerebrosidase.

Front 14

Orphan Drug Act

Back 14

If you develop a therapy for an orphan disease, you get protection from competition where no one can make a generic kind of the drug within 7 years.

Front 15

Gene therapy

Back 15

Use a vector to shuttle gene into your patient, so no need for enzyme therapy.

Front 16

How can viruses be used for gene therapy?

Back 16

Remove virus DNA and put in the genes you want to be expressed

Use retrovirus, adenovirus

Front 17

Naked/plasmid DNA or lipofection

Back 17

take raw DNA and inject it into people

Front 18

When was gene therapy first introduced?

Back 18

1989 and has since exploded

Only a few have gone to phase III

Front 19

Phases of genetic testing

Back 19

Phase I: normal people and make sure it's safe

Phase II: test to see if it works on affected people

Phase III: show your drug works better than other drugs on the market.

Front 20

Severe combined immunodeficiency (SCID) trial

Back 20

1. Born w/o WBCs
2. Young boys, "bubble boy"
3. Deficient in gamma chain of interleukin-1

Front 21

How was gene therapy used to cure SCID?

Back 21

Take stem cells from patients-->expose them to a retrovirus-->virus integrates itself into the genome of each stem cells-->cells are infused into patients-->few stem cells set up shop and start producing RBC and WBC.

Front 22

Most of the SCIID gene therapy patients were cured. But 4/11 developed Leukemia

Back 22

The virus hopped into the LMO-2 gene which causes leukemia

Front 23

Utilitzation of a non-integrating virus vector for gene transfer: Adenovirus based system

Back 23

Virus enters nucleus to deliver DNA, but not necessarily in chromosome. So does not integrate. This is good because it prevent activation of bad genes or inactivation of good genes.

Front 24

What is the limitations to adenovirus based systems for gene therapy?

Back 24

When the cell replicates, this DNA is not replicated and passed on. Eventualy, the genes will become diluted with time.

Front 25

Adenovirus is good for what type of cells?

Back 25

Therefore, adenoviruses good for cells that don't divide (nerves, liver and heart cells, skeletal muscles)

Front 26

LacZ gene

Back 26

Indicator gene

Can see which cells successfully took up the virus and thus the gene was delivered.

Front 27

Gelsinger Tragedy

Back 27

18 year old male withpartial Ornithine Transcarbamylase (OTC deficiency)

Disease where generate high levels of ammonia

Died due to inflammation 3 days after injection.

Front 28

What have we learned from the Gelsinger Tradedy?

Back 28

1. Is gene therapy too risky
2. Failure of consent to disclose corporate sponsorship
3. Failure to disclose adverse non-human primate results