Small molecules
Drugs that are approved to
either: treat other diseases (these can compensate for the functional deficits caused by genetic disorders)
or: treat the specific genetic disorder

EXAMPLE - Marfan Syndrome - a disorder of fibrillin, heart defects, skeletal defects, abnormally tall/thin stature
Treatment: Losartan
Angiotensin II Type I receptor antagonist

Widely used to treat hypertension

Clinical trials underway for Marfan Syndrome
Outcomes so far: reduction in enlargement of aortic root, reduction in serum TGF-beta levels (too high in Marfans because of lack of sequestering of TGF-beta by fibrillin)

Molecular Chaperons
Proteins that can: stabilise unfolded proteins, unfold them, translocate them across membranes, take them to be degraded, or assist with their proper folding or assembly.

They play a role in proteostasis:
"The concept that there are competing and integrated biological pathways within cells that control the biogenesis, folding, trafficking and degradation of proteins present within and outside the cell"

EXAMPLE - Cystic Fibrosis - caused by mutation in CFTR gene causing faulty CFTR ion channels that move sodium and chloride across epithelial membranes

F508Del - most common mutation
Affects folding of the CFTR protein and trafficking to the cell surface
HSC70 and HSP70 are molecular chaperons
HSC70 ubiquitinates mutant CFTR so that it is degraded
HSP70 helps fold CFTR to rescue some of the mutant phenotype

These molecular chaperons can be modulated to reduce some of the symptoms of CF:

Chemical Matrine downregulates the expression of HSC70, rescuing some of the mutant CFTR from degradation
Restores CFTR trafficking

Monoclonal Antibody (mAbs)

Target specific proteins
Inhibit or activate protein function

	Created by Ellie Quinn over 11 years ago

Note on Treatment of Genetic Disease, created by Ellie Quinn on 02/12/2014.