Treatments of genetic diseases Flashcards
What is the largest group of genetic disease?
Inborn errors of metabolism - affect a variety of pathways such as carbohydrate, fatty acid, and protein synthesis mainly due to lacking particular enzyme. Examples include:
- PKU
- MCAD deficiency
- Maple syrup urine disease
- Homocystinuria
What is PKU and how is it treated?
Phenylketonuria - inability to convert phenylalanine to phenylketones due to a lack of phenylalanine hydroxylase. Causes major cognitive impairment, behavioural diseases, recurring vomiting, lack of melanin.
Treated with a low protein diet and tyrosine supplement.
What is haemophilia and how is it treated?
Blood clotting disorder leading to uncontrolled bleeding internally including bleeding into joints and brain.
The main treatment for severe hemophilia involves receiving replacement of the specific clotting factor that you need through a tube placed in a vein.
Give 4 other diseases treated by replacement
- Growth hormone deficiency - GH
- Lysosomal storage diseases
- Fabry disease - recombinant alpha galactosidase A
- Pompe disease - Alpha glucosidase
What are the stages involved in drug development?
- Preclincal/ discovery stage
- Animal testing
- Phase 1 clinical testing less than 100 health volunteers
- Phase 2 100-300 with a few patients
- Phase 3 200-3000 large scale therapeutic trial
- EMA/FDA approval
What organisation approves drugs in England and Wales?
NICE
What organisation approves drugs in Scotland?
Healthcare improvement Scotland
What is a pharmacological chaperone?
A pharmacological chaperone is a drug that acts as a protein chaperone. It contains small molecules that enter cells and serve as a molecular scaffolding in order to cause otherwise-misfolded mutant proteins to fold and route correctly within the cell.
What is a pharmacological modulator?
Receptor activators and inactivators are called agonists. Modulators are either positive, negative or neutral. Positive types increase and negative types lower the probability that an agonist will bind to a receptor (i.e. affinity) and its ability to activate/inactivate the receptor. Neutral types don’t affect agonist activity, but can stop other modulators from binding to a receptor. Some modulators also work as allosteric agonists. Modulators and agonists can be called receptor ligands.[2]
What is stop codon read through therapy?
Some diseases are caused by non-sense mutations that lead to a premature stop codon preventing protein production. Some drugs can be used to prevent this. For example ataluren is used to treat DMD. The premature step is read through allowing the protein to be produced.
What is gene therapy?
Gene therapy is about controlling disease through modifying genes.
If someone has a recessive disease then the defective gene can be replaced. If someone has a dominant disease then the defective gene can be deleted.
What are the difficulties associated with gene therapy?
- Achieving specificity
2. Getting therapy to right place to maintain expression
What is mitochondrially inherited disease therapy?
Requires IVF, takes DNA from fertilised patient egg and transfers to donor egg normal mitochondria.
What is virus gene therapy?
We can engineer viruses to carry therapeutic genes into target cells. Virus choice depends on target tissue but the amount of DNA is limited depending on the virus.
What is CAR-T cell therapy?
Used to treat certain forms of lymphoma and is based upon the production of a chimeric T cell receptor. A T cell receptor is taken and bound to an antibody increasing the affinity to an antigen and recognises the antigen without costimulatory molecules. This allows the T cells to trigger a cellular response. Only approved for treatment after other options have been used since it causes a lot of side effects such as cytokine release syndrome.
