Treatment of Genetic Disease Flashcards

1
Q

Why is it difficult to cure genetic disease

A

Because every single cell in your body is fucked

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2
Q

Trisomy Treatment

A

Supportive care and better cardiac surgery has increased mean survival from 25 to 49

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3
Q

Multiple Endocrine Neoplasia Treatment

A

Genetic testing for autosomal dominant mutations IDs presymptomatic carrier –> take out thyroid (prevent thyroid carcinoma)

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4
Q

Multiple Endocrine Neoplasia - inheritance pattern?

how does genetic relate?

A

Autosomal dominant

Use genetic testing to manage disease (remove thyroid if have mutation)

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5
Q

Metabolic diseases

Usual inheritance pattern

A

autosomal recessive

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6
Q
Metabolic diseases (e.g. PKU)
How do we target?
A

Newborn screening

Diet modification - low phenylalanine diet

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7
Q

How can we target alpha-1 AT?

A

Protein replacement therapy

Recombinant AT1 therapy

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8
Q

How can we target Fabry disease?

A

Alpha galactosidase

Protein replacement therapy

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9
Q

My patient has G6PD deficiency, what would I tell him to avoid?

A

Antimalarial drugs

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10
Q

My patient has Acute intermittent porphyria, what would I tell him to avoid?

A

Barbiturates

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11
Q

My patient has PKU, what would I tell them to avoid?

A

Phenylalanine

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12
Q

My patient has Galactosemia, what would I tell them to avoid?

A

Galactose

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13
Q

My patient has Congenital hypothyroidism, what would I give them

A

Thyroxine

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14
Q

My patient has biotinidase deficiency, what woudl I give them

A

Biotin

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15
Q

My patient has Urea cycle deficieny, what would I give them

A

Sodium benzoate

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16
Q

My patient is heterozygous for hypercholesterolemia
what diversion would I give them
what inhibitor would I give them?

A

oral resin diversion

statin drug inhibition

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17
Q

My patient is homozygous for hypercholesterolemia, what depletor would I give them

A

LDL apheresis

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18
Q

Target at level of mutant protein

What would I give homocystinuria patient?

A

pyridoxine
50% respond
cofactor replacement

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19
Q

What would I give my patient with hemophilia?

A

factor VIII

extracellular replacement

20
Q

What would I give my patient with alpha-1 AD?

A

Alpha-1 Antitrypsin

extracellular replacement

21
Q

What would I given my patient with ADA deficiceny?

A

ADA (adenosine deaminase)

Intracellular

22
Q

Protein targets for Guacher and Fabry are examples of ?

A

Intracellular protein targeting

23
Q

Chaperone therapy?

A

Chemical chaperones assist in proper protein folding

24
Q

Example of chaperone therapy?

A

mutant-alpha-galactosidase A

Fabry disease

25
Q

Protein replacement mainly helps what kind of illnesses?

A

autosomal recessive

26
Q

challenges of protein based therapy?

A
production
delivery
targeting 
immune
cost
27
Q

Farnesyl Transferase Inhibitors in Progeria is an example of?

A

Compensation of Functional defects with novel drugs

28
Q

How do Farnesyl Transferase Inhibitors work in Progeria?

A

Prevent Lamin A/C protein product (Progerin) from sequestration at the nuclear membrane

29
Q

Gene Therapy

Approaches? (3)

A

Non-viral (liposome, direct DNA)
Adenoviral (DNA virus)
Retroviral (RNA virus)

30
Q

Retroviral Gene Therapy

Advantage?

A

Integrate into cell genome

Minimal host immune reactions

31
Q

Retroviral

Disadvantage?

A

Insert limited to 7-8kb

Infect only dividing cells (cannot reach quiescent tissue)

32
Q

Retroviral

Safety?

A

Risk of insertional mutageneis / germline integration

33
Q

Retroviral

Efficiency?

A

Titers of retroviruses relatively low

Efficient at infecting dividing cells

34
Q

Retroviral

Duration?

A

As these integrate into genomic DNA, the transgene can be passed to daughter cells

35
Q

Adenoviral

Advantage?

A

Wide variety of cell types can be infected
Transgene insert size can be 35-36kb
Stable and easy to get high titers

36
Q

Adenoviral

Disadvantage?

A

Does not integrate into cell genome
Expression can be very transient
Some risk of malignant transformation

37
Q

Adenoviral

Safety?

A

Lower risk of insertional mutagenesis

Immune reactions can be severe

38
Q

Adenoviral

Efficiency?

A

Can infect non-dividing cells

Higher titers are possible

39
Q

Adenoviral

Duration?

A

Typically short lived effect; not passed to daughter cells

40
Q

Non viral

Advantage?

A

Insert size can be very large
Could deliver mini-chromosomes
Minimal host immune response

41
Q

Non viral

Disadvantages?

A

Low efficiency

Transient expression

42
Q

Non viral

Safety?

A

Safest?

Does not integrate into host genome

43
Q

Non Viral

Efficiency

A

Often degraded by cellular mechanism - so non specific uptake is inefficient process

44
Q

Non Viral

Duration?

A

Typically short lived effect

Not passed to daughter cell lines

45
Q

Gene therapy approaches include what two broad strategies?

A

In vivo - ex vivo