Treatment of Genetic Diseases

Question 1

Why does deficient genetic treatment occur?

Answer 1

1. gene is not identified or pathogenesis is not understood
   
   • the mutant locus is unknown
2. prediagnostic fetal damage
   
   • the disease occurs too early in the development
3. severe phenotypes are less amenable to intervention
   
   • if patient is too severe there may be no longer a viable good protein.

Question 2

How do you treat Familial Hypercholesterolemia heterozygotes?

Answer 2

combined use of:

1. cholestyramine: a bile acid-binding resin
2. HMG CoA reductase: an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase

Question 3

What is the most common cause of Vitamin-responsive enzyme defects?

Answer 3

due to mutations that reduce the normal affinity (top) of the enzyme protein (apoenzyme) for the cofactor needed to activate it

Question 4

What does PTC treatment use?

Answer 4

Ataluren

Question 5

What does Ataluren do?

Answer 5

It is a new drug designed to enable the formation of a functioning protein in patients with genetic disorders due a nonsense mutation

Question 6

What is protein augmentation?

Answer 6

it is used in proteins whose principal site of action is in the plasma or extracellular fluid

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Question 7

What disease is treated with protein augmentation?

Answer 7

Hemophilia and Alpha-1-Antitrypsin Deficiency

Question 8

How is protein augmentation used in Hemophiliacs?

Answer 8

Patients are treated with an infusion with plasma fractions enriched for factor VIII; replacing an extracellular protein: a1-antitrypsin deficiency

Question 9

What is Adenosine Deaminase Deficiency (ADA deficiency)?

Answer 9

Is a deficiency that results in an accumulation of deoxyadenosine, which, in turn, leads to: a build up of dATP in all cells, which inhibits ribonucleotide reductase and prevents DNA synthesis, so cells are unable to divide

Question 10

What does Adenosine Deaminase do?

Answer 10

It converts adenosine to inosine and deoxyadenosice to deoxyinosine.

Question 11

What are the most susceptible cells to ADA deficiency? and why?

Answer 11

T cells and B cells, because they are among the most mitotically active cells.

Question 12

How are patients with ADA deficiency treated?

Answer 12

With bone marrow transplantation & ERT

Question 13

What is Gaucher’s Disease?

Answer 13

Its a lysosomal storage disorder due to a deficiency of glucocerebrosidase

Question 14

What inheritance is Gaucher’s Disease?

Answer 14

Autosomal Recessive

Question 15

What population is most prevalent to Gaucher’s Disease?

Answer 15

Ashkenazi Jews

Question 16

What gene is affected in Gaucher’s disease?

Answer 16

Lysosomal Cerebrosidase

Question 17

What kind of gene is lysosomal cerebrosidase?

Answer 17

housekeeping gene

Question 18

In Gauchers disease

In what organelle does glucerebrosidase accumulate? What type of cell is mostly affected?

Answer 18

It accumulates in Lysosomes and usually in Macrophages

Question 19

What does the accumulation of glucocerebrosides in lysosomes of macrophages cause?

Answer 19

enlargement of the liver and spleen; also replacement of the bone marrow by lipid-laden macrophages.

Compromises production of RBC’s and platelets leading to anemia and thrombocytopenia

Question 20

What is Enzyme Replacement Therapy?

Answer 20

Is a targeted augmentation of an intracellular enzyme

Question 21

What is Decitabine use for and how does it work?

Answer 21

Is use for Sickel Cell patients. Its function is to decrease the methylation that occurs on CpG.

Question 22

What is deficient in Krabbe Disease?

Answer 22

B-galactocerebrosidase

Question 23

What is the early and late onset of Krabbe?

Answer 23

Early: first month and die before age 2

Late: 6 months and die before age 3

Question 24

What is nuclear transplantation?

Answer 24

Transfer of diploid nucleus from an adult donor somatic cell into an oocyte cytoplasm to generate a cloned embryo.

Question 25

What is reproductive cloning?

Answer 25

Reimplanting an embryo obtained by nuclear transplantation into the uterus of a surrogate mother.

Question 26

What is therapeutic cloning?

Answer 26

Use of embryonic stem cells to form differentiated cell types of the body in culture i.e. grow an ear or kidney etc…

Question 27

Why is cord blood better than bone marrow?

Answer 27

Is more tolerant of histo-incompatible blood than donor cell.

Wide availability of cord blood.

Question 28

What are the risk of insertional mutagenesis?

Answer 28

Cancer, oncogene activation, inactivation of tumor suppressor etc.

Question 29

What is the role of retrovirus in DNA transfer?

Answer 29

target cell must undergo division for integration to occur

Question 30

What is the role of adenoviruses?

Answer 30

infect a wide variety of dividing and nondividing cells

Question 31

What is the role of adeno-associated viruses?

Answer 31

Widespread in humnas so no adverse immune effects. Use to TX Hemophilliacs B patients