Pharmalogical approaches

Last Updated on Wednesday, 10 February 2010 15:31

Enzyme replacement therapies (ERT):

This program involves the injection of replacement enzymes : Recombinant enzymes are injected in order to replace the missing enzymes. In Europe, several diseases benefit from this type of therapy, notably Gaucher Disease Type I and Fabry Disease. Clinical trials are ongoing for Mucopolysaccharidosis Types I, II and IV and for infantile and juvenile forms of Glycogenosis Type II.

Trials also should soon be starting for Niemann-Pick Disease, Type B.
Synthesis of the recombinant enzyme for Sanfilippo Disease has already been achieved. The main limiting factor in its effectiveness is the inability to deliver it to the brain : at present the medication used in ERT cannot cross the hemato-encephalic barrier (Blood-Brain Barrier) and can thus only bring relief for the physical ailments due to the disease, without treating the central nervous system.
Scientists are now researching ways of bypassing this problem . Their strategy includes looking for new receptors, changing the degree of permeability of the hemato-encephalic barrier, using the process of transcytosis, or administering an intracerebral injection in which a small injection chamber would be used to avoid repeated blood sampling/blood loss.
The chamber would be placed under general anaesthesia. It would be like a little bag in the abdomen, under the skin, with a tube the width of a thread leading all the way up to the brain. (The same system is used for chemotherapy ; except that the thread used for chemotherapy does not need to stay in place for long, whereas in this case it does)

Stop Codon Readthrough:

Certain compounds, such as aminoglycosides, are able to prevent the premature termination of protein production that is caused by a nonsense mutation. The principle of Readthrough is to eliminate a stop codon during the translation of ARN and re-establishing part of the production of the deficient enzyme.

Use of Chemical Molecular Chaperones which are specific to the Active Site (of the enzyme):

The increase in residual activity seems a promising lead, for some patients at least (i.e. for the usage of galactose in certain cases of Fabry Disease).
This lead could probably be used against nonsense mutations. It has yet been little explored with reference to Sanfilippo Disease, but could prove to have a very great potential in the long-run.
These research programs give us all a glimmer of hope, but we cannot wait passively for their results. We must contribute as actively as we can to make them progress as fast as possible: In the meantime the disease moves steadily on.