[CIS PIDD] [cis-pidd] PTC, NMD, read-through and PIDs

[Armando Partida Gaytán]

Dear colleagues:

I hope you find this e-mail worthfull to read, and with some luck to
capture the interest of those who may be able to study this formally in the
field of PIDs.

1) premature termination codons (PTC) are frequently responsible of PIDs

2) human cells have diverse molecular adaptive mechanisms, two of them
which i want to mention:

A) NMD - nonsense mediated decay - which is responsible for unstable RNA
"degradation" and so non-translation of truncated proteins.
And
B) Read-through transcription/translation - in which the cell is able to
translate a full-length and functional protein no matter the existence of a
premature stop codon.

3) different experiments (in vitro including ataxia telangiectasia, cystic
fibrosis and also a murine model of Rett syndrome), had proveen the
possibility of inhibiting NMD, thus enhancing the Read-through mechanisms
and being able to express full-length and functional protein,
aminoglycosides (kind of toxic option) amlexanox (seems to be safer) and
other drugs.

It seems to me that PIDs are logical models to give proof of concept of
hypothesis generated by these interesting observations. Specially because
at least in Rett syndrome and A-T two factors decrease the possible benefit
of such therapy (blood-brain barrier / constitutive expression of the
protein, respectively).

Perhaps not visualizing the option as a definite treatment but rather a
"stabilization bridge" to buy time, while definitive treatment comes
available, might worth studying it.

Salutes from Mexico, with respect and hoping to read comments.

*For further reading and appropiate individual citing of mentioned studies:*

Annu. Rev. Genomics Hum. Genet. 2014. 15:8.1–8.24

-- 
Armando Partida Gaytán
e.diuxe at gmail.com
dr.partida.g at gmail.com

*Alergia e Inmunología Clínica Pediátrica*
*Hospital Infantil de México Federico Gómez*
*Inmunodeficiencias Primarias*
*Instituto Nacional de Pediatría*
*Maestría en Ciencias Médicas*
*Universidad Nacional Autónoma de México*

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