Emerging Treatments

Question 1

What are examples of inborn errors of metabolism

Answer 1

PKU

MCAD deficinecy

Maple syrup Urine Disease

Normally because of lack of enzyme

Question 2

Phenylketonuria

Answer 2

No phenylalalnine hydroxylase

Phenylalanine converts to phenylketones

Untreated PKU - major cognitive impairments, behavioural difficulties, fairer skin, hair and eyes, lack of melanin, vomitting

Question 3

How do we treat PKI

Answer 3

Low protein diet - tyrosine supplement

Question 4

What is haemophilia

Answer 4

Blood clottign disorder

Uncontrolled bleeding

Bleeding into joints

Bleeding into brain

Internal bleeding

Fatal if untreated

Question 5

Haemophilia treatement

Question 6

Other disease treated by replacevment

Answer 6

Growht hormone recombinant

Lyosomal storage disease - fabry disease - injection recombinant alpha galactosidase, pompe disease - injection of alpha glucosidase

Question 7

What are pharmacological chaperones

Question 8

Fabry disease pharmacological chaperones

Answer 8

Deficiency of a galactosidase

Build up of glovotriaosylceramide

Migalastat small molecule chaperone

Stabilises enzyme in correct shape

Question 10

What are pharmacological modulators

Answer 10

Agonists/ antagonist

Ion channel activators/blockers

Bcl-abl Kinase inhibitorys (philadelphia chromosome)

Question 11

Cystic fibrosis pharmacological modulators

Answer 11

Defective chloride channel

Design a drug which causes activation - ivacaftor

Orkambi - chaperone and activator

Question 12

What drugs are for stop codons

Question 13

DMD treatment

Answer 13

Premature stop

DMD - BMD

Ataluren is the drug

Question 14

Is gene therapy better in in vitro, ex vivo or in vivo

Answer 14

In vivo is the hardest

Question 15

How does mitochondrially inherited disease therapy

Answer 15

Requires IVF

Take DNA from fertilised patient egg

Take fertilised egg - remove pronucleus and put into donor egg

Question 16

What is virus gene therapy

Answer 16

Engineer virus to carry therapeutic gene

AAV, Adenovirus, HIV, lentivirus and Vaccinia used

Depends on target tissue

Question 17

What is in vitro gene therpay SCID

Answer 17

Severe combnined immuno deficiency

B cell adn T cell lack

X linked (70%) Adenosine deaminase deficinecy (15%)

Can be treated with bone marrow transplant

Question 18

What is the in vitro gene therapy for ADA-SCID

Answer 18

Strimvelis

Isolate hemopoietic stem cells

Isolate and expand CD34

Grow transformed cells

Question 19

In vivo therapy supplement

Answer 19

Useful lack of a functional gene

Use virus to carry in working copy

Inject systemically

Inject locally - eye, spine, brain

Many trea

Question 20

Treatment for leber congenital amaurosis type 2

Answer 20

Recessive disease caused by mutation RPE65

Progressive blindness - loss of retinal

Luxturna rAAV2 expressing RPE65 - single stranded, cannot replicate

Question 21

Anti-sense oligonucleotides

Answer 21

Short nucleic acid complementary to target

Modification prevents degradation

Block translation

Alter splicing pattern

Relative r

Question 22

What is in vivo therapy knockdown

Answer 22

Useful for disease caused by gain of function

Inotersen - transthyretin-related hereditary amloidosis, mutation in TTH, TTH cannot form tetramers instead forms aggregates

Question 23

What is econ skipping

Answer 23

Pre-RNA processing

Oligonucleotides cause exon to be skipped

Exon skipped musn’t be vital

Generally only large proteins

Question 24

Exon skipping DMD

Answer 24

Eteplirsen - oligonucletodie causes skipping exon 51

Result in production of partially active dystrophin

Question 25

CRISPR-Cas9

Answer 25

Bacterial system - disabel bacteriopahges

CAS9 - endonuclease - cut within DNA

Gene editing correct relatively small errors

Non-homologous end joing, homolgy directed repair

Question 26

What is the only example fo CRISPR-Cas9

Answer 26

Deleted CCR5 in twins

CCR5 used in HIV