Gene Therapy Presentations Flashcards
What treatments are currently being prescribed for DMD?
Symptom-specific treatments, corticosteroids, dystrophin restoration therapies like exon-skipping drugs
What gene therapies are currently in clinical trials for DMD?
Two phase III trials (Pfizer and Sarepta) using AAV technologies to deliver a mini-dystrophin gene and a micro-dystrophin gene
Who is the target audience for DMD gene therapies?
Ambulatory males between the ages of 4 and 7
What gene therapies are available for SMA?
Spinraza (Biogen), Zolgensma (Novartis), and Evrysdi (Genentech/Roche)
How do the gene therapies for SMA work?
By upregulating SMN production either through splicing modifier or antisense oligonucleotide targeting SMN2 or AAV9-delivery of SMN gene
What are the mechanisms behind the gene therapies designed for CF?
helps keep dysfunctional CFTR proteins open; recruits more CFTR proteins to the cell’s surface
What are the mechanisms of gene therapies in development for Huntington disease?
Antisense oligonucleotides (binds to faulty HTT gene and blocks ability to produce toxic protein) and microRNAs (reduces the levels of toxic proteins causing HD)
What is the difference in dosing between microRNAs and antisense oligonucleotides?
ASOs require multiple doses whereas microRNAs theoretically only need to be delivered once
What are the causative genes associated with Hemophilia A/B?
Factor VIII (F8) is linked to Hemophilia A and Factor IX (F9) is linked to Hemophilia B
What gene therapy technology is being used to target hemophilia?
AAV5 and AAV6, targeting expression of F8 or F9 in the liver
Who is the target audience for hemophilia gene therapy?
Men who are 18y/o or older
What treatments are currently available for sickle cell disease (not gene therapies)?
RBC transfusions, hydroxyurea, L-glutamine, allogenic stem cell transplantation, management of symptoms
What mechanisms do sickle cell gene therapies use?
Gene addition, gene editing, gene silencing, and gene correction
