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• p53 pathway activation by telomere attrition in X-DC primary fibroblasts occurs in
Most relevant
the absence of ribosome biogenesis failure and as a consequence of DNA damage.
scientific c J, G a, M-G c, P-b l, P r. Clin Transl
arrilloonzálezanGuánarcíaintadoernincheserona
articles
Oncol. 2013 Sep 25. [Epub ahead of print] PMID:24065372.

• Targeting Chk2 improves gastric cancer chemotherapy by impairing DNA dama-

ge repair. Gutiérrez-González a, belda-iniesta c, barGiela-iParraGuirre J, doMinGuez G,
García alFonso P, Perona r, sanchez-Perez i. Apoptosis. 2013 Mar;18(3):347-60. doi:

10.1007/s10495-012-0794-2. PMID:23271172.

Highlights
GSE24.2 a peptide corresponding to an internal domain of Dyskerin (a protein
member of the telomerase complex) has proved to induce telomerase activity by

stabilizing hTR (The RNA component of telomerase) and increasing expression of

TERT (The catalytic subunit of telomerase). GSE24.2 (Gestelmir) has been recent-
ly approved by EMA for the treatment of Dyskeratosis congenita (DC). Expression

of GSE24.2 in human fibroblast is able to protect from DNA damage detected by
decreased H2AX foci and ATM and CHK2 phosphorylation. Due to these findings

we have explored the use of GSE24.2 in ataxia telangiectasia human cells and

studied the consequences in both DNA damage and ROS production. We have
used both fibroblast and lymphoblast cell lines obtained from Corriel carrying

different mutation in the ATM gene. Infection of A-T human cells with lentiviral

vectors expressing GSE24.2 showed a reduction in basal levels of DNA damage,
decreased levels of ROS, proinflammatory cytokines, and also lower levels of p38

phosphorylation, than cells infected with control virus. Finally infection of AT cells

with GSE24.2 is able to rescue these cells from senescence. We have also found
that a shorter peptide than the complete GSE24.2 is also able to perfomr similar

activities in Atcells. GSE24.2 and GSE4 loaded NPs could be delivered to AT and
DC cells, and therefore, become an effective approach for the treatment of DC

and other defective telomerase syndromes. As well as other diseases, harboring

oxidative stress and inflammation.

We have cover the intellectual property of both nanoparticles and also the shorter
version of the GSE24.2 peptide as well as the activities on oxidative stress and

inflammation with two patents presented this year.

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