Treatment of Genetic Diseases Flashcards
What is a phase 1 vs phase 2 vs phase 3 clinical trial?
Phase 1: Testing of pharmacokinetics + safety in healthy individuals
Phase 2: Test for safety / efficacy in hundreds of patients
Phase 3: Test for safety / efficacy in multiple randomized control trials
How does exon-skipping for Duchenne muscular dystrophy work?
Use antisense oligonucleotide to allow exon skipping to allow synthesis of partially functional dystrophin protein.
What is an example of augmentation therapy?
Providing insulin in Type 1 diabetes -> augment with what’s missing
Or, enzyme replacement therapy
What type of therapy is a bone marrow transplant?
An augmentation therapy
What is a small molecule drug and give an example?
Drug that binds to a specific target protein, fitting into a key position of the protein structure, blocking the function of the protein which is key to pathogenesis
i.e. in CF, a drug which helps re-open the closed chloride channel in some etiologies
What are two ways in which genetic engineering brings us drugs? Give examples of each.
- Recombinant protein - insulin
2. Monoclonal antibodies - panitumumab - bind EGFR
How do enzymes get into cells during enzyme replacement therapy?
Internalized via receptors on cell surface to reach target site
What is the major limitation to enzyme replacement therapy?
Cannot cross blood brain barrier
Antibodies via immune system can decrease effectiveness
Why is substrate reduction therapy so gud?
Potential to cross blood-brain barrier and thus treat CNS symptoms, by restoring the balance between synthesis and degradation of a storage material
What is chaperone therapy?
Small molecules that bind and stabilize lysosomal enzymes, mutation specific and designed only to be used in combination with ERT
How does hematopoeitic stem cell transplantation work? What are the risks?
Early, presymptomatic intervention with newborns that allows the cross production of enzyme to be delivered to neurons via microglial cells
Risks are similar to any other transplant therapy
What is the idea behind gene therapy?
Gene modification of cells by inserting DNA or RNA into a recombinant vector, then tackling the problem of how to get it to target tissue
What type of cells are targeted in gene therapy? Give one disorder it has been successful in.
Somatic only - not germline
Was successful in treating severe combined immunodeficiency (SCID)
How does RNA interference work? Give one disease
Repression of gene of interest by inhibiting mutant gene expression without affecting normal allele
Huntington’s - bind to CAG repeats to deactivate abnormal gene
How does CRISPR-Cas9 work?
Targets DNA / RNA, and can selectively excise gene gene elements. Potential ethical concerns
