Emerging Treatments Flashcards
What are examples of inborn errors of metabolism
PKU
MCAD deficinecy
Maple syrup Urine Disease
Normally because of lack of enzyme
Phenylketonuria
No phenylalalnine hydroxylase
Phenylalanine converts to phenylketones
Untreated PKU - major cognitive impairments, behavioural difficulties, fairer skin, hair and eyes, lack of melanin, vomitting
How do we treat PKI
Low protein diet - tyrosine supplement
What is haemophilia
Blood clottign disorder
Uncontrolled bleeding
Bleeding into joints
Bleeding into brain
Internal bleeding
Fatal if untreated
Haemophilia treatement
Other disease treated by replacevment
Growht hormone recombinant
Lyosomal storage disease - fabry disease - injection recombinant alpha galactosidase, pompe disease - injection of alpha glucosidase
What are pharmacological chaperones
Fabry disease pharmacological chaperones
Deficiency of a galactosidase
Build up of glovotriaosylceramide
Migalastat small molecule chaperone
Stabilises enzyme in correct shape
What are pharmacological modulators
Agonists/ antagonist
Ion channel activators/blockers
Bcl-abl Kinase inhibitorys (philadelphia chromosome)
Cystic fibrosis pharmacological modulators
Defective chloride channel
Design a drug which causes activation - ivacaftor
Orkambi - chaperone and activator
What drugs are for stop codons
DMD treatment
Premature stop
DMD - BMD
Ataluren is the drug
Is gene therapy better in in vitro, ex vivo or in vivo
In vivo is the hardest
How does mitochondrially inherited disease therapy
Requires IVF
Take DNA from fertilised patient egg
Take fertilised egg - remove pronucleus and put into donor egg
What is virus gene therapy
Engineer virus to carry therapeutic gene
AAV, Adenovirus, HIV, lentivirus and Vaccinia used
Depends on target tissue
What is in vitro gene therpay SCID
Severe combnined immuno deficiency
B cell adn T cell lack
X linked (70%) Adenosine deaminase deficinecy (15%)
Can be treated with bone marrow transplant
What is the in vitro gene therapy for ADA-SCID
Strimvelis
Isolate hemopoietic stem cells
Isolate and expand CD34
Grow transformed cells
In vivo therapy supplement
Useful lack of a functional gene
Use virus to carry in working copy
Inject systemically
Inject locally - eye, spine, brain
Many trea
Treatment for leber congenital amaurosis type 2
Recessive disease caused by mutation RPE65
Progressive blindness - loss of retinal
Luxturna rAAV2 expressing RPE65 - single stranded, cannot replicate
Anti-sense oligonucleotides
Short nucleic acid complementary to target
Modification prevents degradation
Block translation
Alter splicing pattern
Relative r
What is in vivo therapy knockdown
Useful for disease caused by gain of function
Inotersen - transthyretin-related hereditary amloidosis, mutation in TTH, TTH cannot form tetramers instead forms aggregates
What is econ skipping
Pre-RNA processing
Oligonucleotides cause exon to be skipped
Exon skipped musn’t be vital
Generally only large proteins
Exon skipping DMD
Eteplirsen - oligonucletodie causes skipping exon 51
Result in production of partially active dystrophin
