Treatment of Genetic Diseases Flashcards
Why does deficient genetic treatment occur?
- gene is not identified or pathogenesis is not understood
- the mutant locus is unknown
- prediagnostic fetal damage
- the disease occurs too early in the development
- severe phenotypes are less amenable to intervention
- if patient is too severe there may be no longer a viable good protein.
How do you treat Familial Hypercholesterolemia heterozygotes?
combined use of:
- cholestyramine: a bile acid-binding resin
- HMG CoA reductase: an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase
What is the most common cause of Vitamin-responsive enzyme defects?
due to mutations that reduce the normal affinity (top) of the enzyme protein (apoenzyme) for the cofactor needed to activate it
What does PTC treatment use?
Ataluren
What does Ataluren do?
It is a new drug designed to enable the formation of a functioning protein in patients with genetic disorders due a nonsense mutation
What is protein augmentation?
it is used in proteins whose principal site of action is in the plasma or extracellular fluid
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What disease is treated with protein augmentation?
Hemophilia and Alpha-1-Antitrypsin Deficiency
How is protein augmentation used in Hemophiliacs?
Patients are treated with an infusion with plasma fractions enriched for factor VIII; replacing an extracellular protein: a1-antitrypsin deficiency
What is Adenosine Deaminase Deficiency (ADA deficiency)?
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
What does Adenosine Deaminase do?
It converts adenosine to inosine and deoxyadenosice to deoxyinosine.
What are the most susceptible cells to ADA deficiency? and why?
T cells and B cells, because they are among the most mitotically active cells.
How are patients with ADA deficiency treated?
With bone marrow transplantation & ERT
What is Gaucher’s Disease?
Its a lysosomal storage disorder due to a deficiency of glucocerebrosidase
What inheritance is Gaucher’s Disease?
Autosomal Recessive
What population is most prevalent to Gaucher’s Disease?
Ashkenazi Jews
What gene is affected in Gaucher’s disease?
Lysosomal Cerebrosidase
What kind of gene is lysosomal cerebrosidase?
housekeeping gene
In Gauchers disease
In what organelle does glucerebrosidase accumulate? What type of cell is mostly affected?
It accumulates in Lysosomes and usually in Macrophages
What does the accumulation of glucocerebrosides in lysosomes of macrophages cause?
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
What is Enzyme Replacement Therapy?
Is a targeted augmentation of an intracellular enzyme
What is Decitabine use for and how does it work?
Is use for Sickel Cell patients. Its function is to decrease the methylation that occurs on CpG.
What is deficient in Krabbe Disease?
B-galactocerebrosidase
What is the early and late onset of Krabbe?
Early: first month and die before age 2
Late: 6 months and die before age 3
What is nuclear transplantation?
Transfer of diploid nucleus from an adult donor somatic cell into an oocyte cytoplasm to generate a cloned embryo.
What is reproductive cloning?
Reimplanting an embryo obtained by nuclear transplantation into the uterus of a surrogate mother.
What is therapeutic cloning?
Use of embryonic stem cells to form differentiated cell types of the body in culture i.e. grow an ear or kidney etc…
Why is cord blood better than bone marrow?
Is more tolerant of histo-incompatible blood than donor cell.
Wide availability of cord blood.
What are the risk of insertional mutagenesis?
Cancer, oncogene activation, inactivation of tumor suppressor etc.
What is the role of retrovirus in DNA transfer?
target cell must undergo division for integration to occur
What is the role of adenoviruses?
infect a wide variety of dividing and nondividing cells
What is the role of adeno-associated viruses?
Widespread in humnas so no adverse immune effects. Use to TX Hemophilliacs B patients
