Emerging treatments

Question 1

what courses Inborn errors of metabolism

Answer 1

lack enzyme

Question 2

example sof IEOM

Answer 2

PKU
MCAD Deficiency
Maple Syrup Urine Disease
Homocystinuria

Question 3

effect what pathways

Answer 3

Carbohydrate metab
Fatty acid metab
Proteins metab

Question 4

why does a lack of enzye cause the diseases

Answer 4

lack enzyme means you lack the product

increase in substrate level

cause alternate product

Question 5

what is PKU

Answer 5

Phenylketonuria

Question 6

what is teh lacked enzyme

Answer 6

Phenylalanine

hydroxylase

Question 7

what does Phenylalanine

hydroxylase do

Answer 7

converts Phenylalanine to

Tyrosine

Question 8

consequence

Answer 8

alternate product of Phenylketones

Question 9

what does untreated PKU cause

Answer 9

Major cognitive impairment 
behavioural difficulties
fairer skin, hair and eyes than siblings
     lack of melanin
recurrent vomiting

Question 10

how to treat

Answer 10

Treated with low protein diet – Tyrosine supp.

Question 11

what to do before treatment

Answer 11

Before treatment need to identify cause

Possible before gene identified - biochemistry

Question 12

what is Haemophilia

Answer 12

Blood clotting disorder

Question 13

what does it cause

Answer 13

Uncontrolled bleeding
Bleeding into joints
 excruciating pain
Bleeding into brain
Internal bleeding

Question 14

what happens if it is untreated

Answer 14

fatal

Question 15

major downside of treatment

Answer 15

coontaminated blood

clotting factors contaminated with diseases

Question 16

treatment

Answer 16

– Recombinant Factor VII treatment

Question 17

can you treat other disease by replace missing factor

Answer 17

yes

Question 18

what do Pharmacological Therapies targeting protein treat

Answer 18

Treat the condition not symptoms

Question 19

do they cure

Answer 19

no, only treat so lifelomg

Question 20

what process invlolve molecular chaperones

Answer 20

folding of protiens
they assist in folding or unfolding of protiens
by stabilizing the intermediates

Question 21

what does Migalastat do and what is it

Answer 21

Migalastat small molecule chaperone

Stabilises enzyme in correct shape

Question 22

a cause of Cystic fibrosis

that is treated by Pharmacological Modulators

Answer 22

Defective chloride channel

Mutations (33) cause channel not to open

Design a drug which causes activation - Ivacaftor

Is mutation specific

Question 23

Cystic fibrosis

caused by misfoled thus inactived channel treatment

Answer 23

Treat with combination chaperone and activator

Question 24

what are Pharmacological Modulators

Answer 24

commonly used drugs

Question 25

what do they target

Answer 25

Receptor agonists/antagonist Ion channel activators/blockers

Question 26

what is a by non-sense mutation | and what is causes

Answer 26

-premature stop codon This prevents protein production (smaller protien)

Question 27

how to treat

Answer 27

Stop codon read through

Question 28

example

Answer 28

Aminoglycoside antibiotics bind to ribosome Cause mistranslation Drugs based on these → read through non-sense mutations

Question 29

what is the cause of Duchenne muscular dystrophy

Answer 29

premature stop

Question 30

what is Becker muscular dystrophy

Answer 30

– missing section

Question 31

but they are mutation specific so

Answer 31

Non-sense mutation specific | noyt cure but treat disease not symptoms

Question 32

why is gene therapy harder in pratice

Answer 32

Achieving specificity Getting therapy to right place maintain expression

Question 33

what does in vivo mean

Answer 33

in teh living

Question 34

ex vivo

Answer 34

out the living

Question 35

In vitro

Answer 35

in glass

Question 36

how to carry out Mitochondrially inherited disease therapy

Answer 36

Requires IVF Take DNA from fertilised patient egg Transfer to donor egg normal mitochondria

Question 37

how does Virus gene therapy work

Answer 37

Can Engineer virus to carry therapeutic gene

Question 38

what is viral tropism

Answer 38

affinity to infect certain cell types

Question 39

what does the virus depends on

Answer 39

Virus choice depends on target tissue | Amount of DNA limited depends on virus

Question 40

why are ex vivo treatmnets using virus used to treat mainly the heampotic system

Answer 40

stem cells are easily reached and replaced

Question 41

what is an In vitro gene therapy ADA-SCID | SCID resulting from Adenosine deaminase deficiency

Answer 41

Strimvelis

Question 42

how to carry out

Answer 42

``` Isolate patients Hemopoietic stem cells Isolate and expand CD34+ Transfected with ADA – lentivirus Grow transformed cells Treat patient with busulfan (kill HSC) Reinfused transformed cells into patient ```

Question 43

what are Anti-sense oligonucleotides

Answer 43

Short modified nucleic acid complementary to target | Modification prevents degradation allow entry to cell

Question 44

what do they do

Answer 44

Binds to target Block translation Can also alter splicing

Question 45

advntg

Answer 45

Relatively cheap to make

Question 46

what are they useful for

Answer 46

Useful for diseases caused by gain of function

Question 47

what can they mediate

Answer 47

exon skipping

Question 48

what is it taregt

Answer 48

pre mrna maturation

Question 49

what happens

Answer 49

``` Oligonucleotides cause exon to be skipped Can be used to skip disease causing exon To put RNA back in reading-frame Useful in limited circumstances Exons skipped mustn't be vital Generally only large proteins ```

Question 50

what is CRISPR

Answer 50

Bacterial system disable bacteriophages

Question 51

what isCAS9

Answer 51

- Crispr associated protein 9- Endonuclease | Recognises and Cleaves DNA CRISPR hybrids

Question 52

- things

Answer 52

Gene editing correct relatively small errors Cannot correct large changes deletions, triplet expansion May have off target effects

Question 53

Same problem as other methods

Answer 53

targeting | getting into all cell