Treatment of Genetic Diseases

Question 1

Treating Sngl Gene Disorders v MFD

Answer 1

SNGL- know etiology/affected gene but need treatment over lifetime

MFD- many mult genes and etiology unknown, variation in severity so diff levels of treatment needed

Question 2

3 Structural Abnormalities and How to Treat

Answer 2

1- congenital heart disease
2- cleft palate
3- pyloric stenosis

**Treat w/ surgery

Question 3

Metabolic Disorder Treatments (5)

Answer 3

1- substrate limitation (PKU diet)
2- product replacement (Vit B or Factors in hemophilia)
3- diversion therapy (shunt extra NH3 in urine)
4- pharm inhibition (statins)
5- depletion therapy (directly remove toxin- phlebotomy removes high iron in hemochromatosis)

Question 4

Protein Level Treatments (3)

Answer 4

1- Small molecule therapy - small molecule acts on protein to inc its function
2- Protein augmentation - inc level/conc of already existing protein (just need more)
3- Enzyme Replacement Therapy - may chemically modify/enhance enzyme beforehand

Question 5

Ways of Modulating Gene Expression (3)

Answer 5

1- Inc gene expression at wildtype or mutant locus (inc transcription of normal gene or of mutant gene if it has some functional ability)

2- Inc gene expression at non-disease locus (inc transcription at different locus that prod another good gene to compensate for bad)

3- Dec gene expression at autosomal dominant gene locus (use RNAi siRNA or shRNA)

Question 6

Ways to Use Transplantation to Treat Genetic Diseases (3) + Issue w/ Each

Answer 6

1- stem cells (unethical?)
2- bone marrow transplant (graft v host, immune suppression and infection)
3- organ transplant (graft v host, immune suppression, infection and organ supply)

Question 7

Ex Vivo v In Vivo Gene Therapy

Answer 7

Ex Vivo- can enrich cells, can test before transplant, eliminate possible immune response beforehand (disadv- limited to cell transplantation applications, expensive)

In Vivo- direct delivery to target cells, can try multiple repeated applications (disadv- must transduce many cells, toxic, immune response, stability)

Question 8

How to decide in vivo or ex vivo…

Answer 8

• disease state
• availability of cells/tissues
• cell type
• what vector is employed - gene size limitation

Question 9

Viral Vectors (7)

Answer 9

1- retrovirus
2- lentivirus 
3- adenovirus 
4- adeno-associated virus
5- herpes simplex 
6- vaccinia virus 
7- measles virus

Question 10

What General Disease Types Can be Treating w/ Gene Therapy? (4)

Answer 10

1- cancer
2- monogenetic diseases
3- MFDs
4- Infectious Disease (vaccines, antisense for HIV, interfere w. virus replication, etc)