Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

// > Emerging Treatments > Flashcards

Emerging Treatments Flashcards

1
Q

What are inborn errors in metabolism generally caused by?

A

Lack of enzyme

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is PKU and if untreated, what can it lead to?

A

Phenylketonuria

Major cognitive impairment

Behavioural difficulties

Fairer skin, hair and eyes than siblings

Lack of melanin

Recurrent vomiting

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Describe the biochemistry behind PKU

A

Phenylalanine is usually converted into Tyrosine, catalysed by Phenylalanine hydroxylase

When the phenylalanine hydroxylase is not produced, Phenylalanine is converted into Phenylketones

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

How can PKU be treated?

A

Through diet (low protein) and Tyrosine supplements

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is Haemophilia?

A

Blood clotting disorder where blood bleeding is uncontrolled and even occurs into joints and brain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

How can Haemophilia be treated and what kind of treatment is this?

A

Through Factor VIII supplements

Treatment by replacement

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

In what case would a pharmacological chaperone be necessary?

A

When there is a fault in the protein folding due to a mutation, leading it down a degradation pathway

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

In Fabry disease, what does the chaperone do and what is it called?

A

Migalastat is a small molecule chaperone that allows accurate folding of protein, stabilising enzyme in correct shape

Preventing the build up of globotriaosylceramide

Also preventing the lack of alpha-galactosidase A

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What does a pharmacological modulator do?

A

Receptor agonist/antagonist

Ion channel activators/blockers

Can be designed to have these effects on mutant receptors or channels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Explain the combination therapy used in Cystic Fibrosis

A

In CF there can be both a mutation leading to a misfolded, inactive channel and a defective chloride channel (channel doesn’t open)

Treated with both chaperone (Lumacaftor) and activator (Ivacaftor)

^^TREATMENT not cure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is a non-sense mutation?

A

Mutation that introduces a stop codon prematurely in the protein sequence

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Does a non-sense mutation prevent protein production?

A

Yes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What class of antibiotics cause a non-sense mutation?

A

Aminoglycosides - bind to ribosomes –> cause mistranslation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

How does a non-sense suppressor work?

A

Allows near cognate aminoacyl-tRNAs to compete with the release factors that lead to the premature stop codon formation

This is a stop codon readthrough

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

How does gene therapy work with recessive diseases?

A

Replace the defective gene

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How does gene therapy work with dominant diseases?

A

Delete the defective gene

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What does ‘in vivo’ and ‘in vitro’ mean?

A

In the living

In glass

18
Q

What is the most well known in vitro gene therapy?

A

Mitochondrially inherited disease therapy

Requires IVF

19
Q

Explain the steps of Maternal spindle transfer

A

Chromosomes are removed from an unfertilised egg that has mutated mitochondrial DNA

These are added to an unfertilised donor egg that has had its nucleus removed

This fused egg is fertilised in vitro

The egg develops normally to form an embryo

[Take DNA from fertilised patient egg and transfer to donor egg normal mitochondria]

20
Q

Explain the steps of pronuclear transfer

A

An egg with mutated mitochondrial DNA is fertilised in vitro

Resulting pronucleus is removed

This is transferred to a fertilised donor egg that has had its pronucleus removed

The fused egg develops normally

21
Q

What is the overall process of virus gene therapy?

A

Removing DNA from virus

Engineering the DNA so that it has a new gene that would benefit the host

Place the DNA back into the virus

Allow it to enter the host cells so that host cells can start transcribing this new DNA

22
Q

What is the virus choice for this type of therapy largely dependent on?

A

target tissue that you want to treat

23
Q

What is meant by viral tropism?

A

affinity for infecting certain cell types that a virus has

24
Q

What is Bubble Baby disease?

A

lack both b-cell and t-cell mediated response –> IMMUNO DEFICIENCY

X-linked (X-SCID)
Adenosine deaminase deficiency (ADA-SCID)

Treated with bone marrow transplant

25
Q

What else limits the amount of DNA injected in viral gene therapy?

A

Size of the virus

26
Q

What types of cells are viral gene therapy most commonly used to treat?

A

Haemopoietic stem cells

They are easy to reach

27
Q

How does in vitro gene therapy for ADA-SCID work?

A

Take the bone marrow from the patient

Isolate the embryonic haemopoietic stem cells (specifically CD 34 positive ones)

Transfect them with lentiviral virus that encodes ADA

Treat patient with busulfan to kill their own haemopoietic stem cells so they can be infused with the transformed cells

These are therefore able to replace the cells lacking ADA and replace them with cells that are healthy

28
Q

Where can local injections of viruses carrying functional genes be injected in vivo?

A

Eye

Spine

Brain

29
Q

Explain how in vivo therapy supplement works for Leber congenital amaurosis type 2

A

recessive disease caused by mutation RPE65 leading to loss of retinal cells (progressive blindness)

Luxuturna rAAV2 (virus) expressing RPE65

Injected into eye at site of mutation

Virus enters retinal cells and produces gene

Greatly improving vision

LIMITATION: Patient needs sufficient remaining retinal cells for this to work

30
Q

Describe what is meant by an antisense oligonucleotide

A

Short modified nucleic acid complementary to target

Modification prevents degradation and allows entry to cell

Binds to target → Blocks translation → Can also alter splicing

31
Q

Explain how antisense oligonucleotides could be used to treat TRHA (transthyretin-related hereditary amyloidosis)

A

Inotersin binds to mRNA that encodes both normal and mutant form of transthyretin

So both are degraded → Can no longer produce protein → doesn’t form aggregates

Slows down progression of disease

32
Q

What is RNAi (siRNA)

A

dsRNA complementary to target

Modification prevents degradation allow entry to cell

activated via Dicer/Risc pathway

targeted RNA cleaved

33
Q

How does exon skipping occur?

A

Antisense oligonucleotide will bind to the acceptor site of exon to prevent it from acting as an exon

Excluding this exon from the protein

34
Q

What is exon skipping used for?

A

To put RNA back in reading-frame

35
Q

What are the requirements for exon skipping to occur?

A

exon being skipped must not be vital for proteins function

Therefore mainly used for larger proteins where a single exon does not largely affect the protein

36
Q

In DMD, what oligonucleotide is used and what does it achieve?

A

Eteplirsen

Results in production of partially active dystrophin

37
Q

What does CRISPR-Cas9 consist of?

A

CRISPR - derived from previous bacteriophage

Cas9 - CRISPR-associated protein 9 - Endonuclease

38
Q

How does CRISPR-Cas9 work?

A

Targets specific regions of genome (CRISPR regions) and cleaves them using the Cas9 protein

39
Q

What are the 2 methods of repair of the genome after CRISPR-Cas9 has acted on it?

A

Non-homologous end joining

Homology directed repair

40
Q

Give an example of a change in genome that CRISPR-Cas9 would not be able to edit?

A

Triplet expansion

41
Q

What is the one case that CRISPR-Cas9 has been used in humans?

A

To alter genome of IVF embryos

Deleted CCR5 in twins

42
Q

A change in which chemokine receptor has been shown to have links with resistance to HIV?

A

CCR5

// (13 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions