6. Clinical Trial of Gene Therapy Flashcards
What are the general gene therapy strategies?
1) Gene augmentation therapy (due to loss of function)
2) Targeted killing of specific cells (cancer)
3) Targeted inhibition of gene expression (inapropriate expression of gene, e.g. CML)
4) Targeted mutation correction
What is an example of germline gene therapy?
Ooplasmic transfer
Remove healthy ooplasm and put in unhealthy ooplasm
Replaces mitochondria
Baby has healthy mitochondira
What points need to be considered for gene therapy trials?
1) Learn about the disease
- good disease for therapy?
2) Design gene therapy
- What tissue?
- how to target (invivo or insitu)
3) Get money and approval for trials
4) Establish safety in humans
What was the first clinical trial using gene therapy?
To treat severe combined immunodeficiency (caused by ADA)
What is adenosine deaminase deficiency? (ADA)
Defective enzyme Adenosine deaminase - breaks down purines
Buildup of substrate
Who was the first gene therapy patient?
Ashanti de silva
What is the most common form of SCID?
X-linked SCID
Mutations in gene encoding common gamma chain
Absence of T-cells and lack of B-cell function
Who does X-SCID typically affect?
boys
life expectancy two years without bone marrow transplant
Where can you get gene therapy treatment for X-scid?
London and Paris
What was the method and outcome of treatment in paris?
7 month median age patients
Infusion of bone marrow - derived autologous CD34+ cells, transduced with y chain-containing retroviral vector
8 patients
4 fine
4 leukemia
3 live
overall 7 sustained immune reconstitution
What is retinal degeneration?
Inherited condition, loss of photoreceptors and RPE cells (retinal pigment epithelium)
What is Leber’s congenital amaurosis?
Linked to RPE mutations
Visual cycle impaired Normal at birth Loss of ERG at 5 months Night and day blind Mutation - truncated protein
What is the name of the gene replaced in Lebers congenital amaurosis?
11-cis retinal
What methods are used to test leber congenital amaurosis response to gene therapy?
ERG functional analysis
Multifocal ERG recordings
Morphometric analysis
Where are some of the clinical trials taking place on LCA2?
Uof Pennsylvania
Uof College London
Uof pennsylvania U of Florida
