Emerging treatments - minimal info Flashcards
What are the three groups genetic treatments can be categorised into?
Treatments of
- replacement
- protein
- genes
When is treatment of replacement usually used?
Due to inborn errors of metabolism
What is an inborn error of metabolism and give examples
Disorders where a substrate cannot be converted into a product
PKU - phenylketonuria - phenylalanine can’t be broken down due to missing enzyme and forms phenylketones
In haemophilia lack of factors VII or IX means they must be replaced otherwise uncontrolled bleeding occurs
Growth hormone deficiency
Fabry disease
Pompe disease
What happens when PKU Is left untreated?
How do you treat it
Major cognitive impairment
behavioural difficulties
fairer skin, hair and eyes - lack of melanin
recurrent vomiting
Treated with low protein diet (less phenylalanine)
When is a pharmacological chaperone used?
In protein targeting treatments when the protein folding complex fails
an agent is produced which binds to the mutant protein, rescues and folds it correctly
What is the issue with fabrys disease treated?
With a pharmacological chaperone
Fabrys disease - α-galactosidase A deficiency causing build up of globotriaosyceramide
Migalasat - small molecule chaperone
What do pharmacological modulators do?
Act as receptor agonists/antagonists to block or activate ion channels
used to decrease number of channels / block pathway for protein substrates
What do stop codon read through drugs do ?
Give an example of where this occurs
Some diseases have premature stop codons which prevent protein production - as the protein produced is short and non-active
Forces DNA Polymerase from stopping at the stop codon
DMD is due to premature stop - stop codon read through bypasses this and converts it into BMD which is less severe
What is a limitation of genetic treatments?
Many are mutation specific
How are pharmacological modulators used to treat cystic fibrosis?
Defective chloride channel - cause it not to open
Ivacaftor drug causes activation of this channel
How is combination therapy used in cystic fibrosis
defective chloride channel
One mutation leads to a misfolded inactive channel
treatment with both chaperone and activator causes it to fold properly and makes it more active which improves lung function
Why is gene therapy difficult?
Hard to achieve specificity
Hard to get therapy to the right place
Hard to maintain expression
How is gene therapy used in mitochondrially inherited diseases?
requires IVF and normal mitochondria from a donor egg - remove DNA from both eggs and insert mothers DNA into the donor egg - approved in the UK but controversial
What is virus gene therapy?
Where we engineer a virus to carry a therapeutic gene to allow the cells to make a missing protein
How do anti-sense oligonucleotides and gene silencing is used?
Prevent production of targeted proteins, effective in neurological disorders
