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Flashcards in MCP 6 Deck (29):

What are two intial categories of intervention for medical concerns sometimes genetic diseases ?

Medical and surgical interventions
Medical includes drug therapy treat symptoms
Surgical - cleft palate repair or transplant surgery


Name the type of disorder that one would use dietary modification to treat and an example?

Metabolic disorders, - classic examples include amino acid catabolism disorders
PKU restricted bland diet that is life long


How would you treat abnormal PKU ?

Supplementation with the missing enzyme
Also called replacement - ex BH4


What is it called when you divert pathway to treat a disorder?

Diversion directing a pathway in another direction to avoid substrate accumulation for urea pathway use sodium benzoate will combine ammonium with glycine to make hippurate which excreted in urine


Name two other treatments for metabolic disorders

inhibition and depletion


Define Inhibition treatment

modifying the rate of synthesis by using a drug or other agent that slows or blocks a critical step in the pathway


define depletion treatment and give an example

removal of a substance that is excess
-hereditary hemochromatosis is the excess accumulation of iron in the blood and can be relieved by regular blood letting or phlebotomy


Treatment at the protein level

replacement -extra cellular -> if a protein is absent add it back (ex; hemophilia A- factor VIII, or alpha 1 antitrypsin deficiency-treat with alpha 1 antitrypsin)


Problems with treatment at the protein level?

cost (have to give many repeated treatments as it is not a permanent fix), availability (may come from animal sources), antibody production in patient and contamination


Treatment at protein level intracellularly issues

replacement must target a specific cell type -> can be very challenging to get it to the right target


Explain treatment at a protein level-enhancing genetic expression and give an example

use of one gene to compensate for the mutation in another
example is sickle cell anemia-> treatment with decitabine increases level of gamma globin in blood which hypermethylates DNA (inhibits methyltransferase) and subsequently turns gamma globulin on -> upregulates HbF which upregulates oxygen carrying -inhibits polymerization of deoxyhemoglobin S


Bone marrow transplantation -uses and process

-hematological disorders
-remove the disease clone and replace it with unaffected cells
-collect bone marrow stem cells fro the patient (autologous) or from matched donor (allogenic)
-transplant cells will re-established in the new host and hopefully cure the disease


What method of treatment is commonly used in lysosomal storage diseases and why?

-bone marrow transplants -> bone marrow is about 10% of the bodys cell mass and extracellular transfer from the normal marrow may stimulate function in other cells
-acts as a source of mononuclear phagocytes
-can reduce the size of various internal organs
-if done within the first 2 years of life will limit the negative effects of neurological ill effects of disease


define stem cells-

-self renewing undifferentiated cells
-can proliferate and produce a wide variety of different types of differentiated cells


Name the two categories of stem cells and their properties

-embryonic SC = pluripotent and capable of differentiating into any cell type in the body
-somatic SC = self renewing but can only differentiate into cell types found in the tissue of origin


What are some problems with allogenic stem cell use?

-immunosupressive drugs required to combat the possibility of graft vs host disease


What are iPS?

induced pluripotent stem cells-> cells collected from an individual and are treated in vivo with "reprogramming factors" to make them into pluripotent state and undo differentiation


Problems with nuclear transfer (cloning) and potential beneficial uses ?

-possible negative effects on genes->they may appear to be the age of the donor instead of the newly freshly minted genes found in embryos -> causing complications and early death as in the case of the dolly the lamb
-potential benefits agriculture, both crops and herds-> selecting for the most genetically hardy crop and most milk producing cow etc.


When do we use nuclear transfer in humans?

-When there is an issue with a woman's egg (carries cytoplasmic deleterious effects) we can extract the donor DNA and input the mother to be's DNA and use the father's sperm to fertilize the egg


Issues with "My friend again" other animal/pet cloning companies?

-may not actually look identical
-things like size, personality can be totally different (personality is a learned behavior, not genetic)


Define gene therapy

-incorporating "normal" functioning genes into the genome
-The deliberate introduction of genetic material into the human somatic cells for therapeutic, prophylactic or diagnostic purposes


What are three general classes of gene therapy usage?

1. correcting a loss of function mutation by incorporating a functional gene into the genome
2. compensating for a deleterious dominant allele by replacing or inactivitating mutant allele
3. Adding genetic material that has a pharmacological effect


What are some requirements for a successful gene therapy?

-identification of gene
-availability of gene sequence or cloned DNA from the gene of interest
-identification of target tissue
-ability to deliver gene to target
-understanding of gene biochemistry
-understanding of expression


What is the biggest limitation of gene therapy ?

-delivering the gene to a target!
-vector must be able to carry the DNA
-must be able to insert the DNA into a target tissue
-usually we use viruses - we can also use liposomes-> can create artificial liposome that carries DNA of interest can go through lipid bilayer and release DNA into cytoplasm once it fuses with lipid membrane (temporary)


What are the two major categories of gene therapy introduction/

-in vivo = genes are incorporated into vectors and targeted to specific cells in body
-ex vivo = cells are extracted from the patent and genetically modified- the altered cells are returned back to the patient


Who should participate in gene therapy treatment?

-individuals with known disease causing mutation but who currently show no symptoms?
-an individual with clinical symptoms of a disease but whom has received standard therapy?
-an individual who has failed standard therapy?
jury is still out-> only those patients who had failed conventional therapy and who had less than 3 months to live were accepted onto new protocols


Antisense DNA therapy

antisense RNA will bind to its homologous sequence and prevent binding of ribosomes etc, thus blocking translation
-useful to down regulate protein production
-cancer characterized by overproduction of a protein
-incorporate an antisense strand into the cells to block translation


RNA interference

-targets mRNA and cuts it up-> thus preventing the production of abnormal proteins, active unit small interfering RNA (siRNA) can be injected or incorporated into cells via vectors
-target degradation of mRNA
-destroy mRNA from negative dominant mutations while leaving the second allele alone
-reduces the concentrations of an mRNA that is over expressed


Name and describe main vector for gene therapy

AAV- adeno-associated virus
-non pathogenic vector
-reduces the likelihood of an immune reaction
-is found in many serotypes-so that the proper vector can be matched to a particular cell type
-non-integrative so will not disrupt cancer genes