Background Huntington's disease (HD) is a devastating disease for which currently no therapy is available. It is a progressive autosomal dominant neurodegenerative disorder that is caused by a CAG repeat expansion in the HD gene which results in an expansion of polyglutamines at the N terminal end of the huntingtin (htt) protein and the accumulation of cytoplasmic and nuclear aggregates in neurons. The polyglutamine expansion results in a toxic gain of function for the huntingtin protein and plays a central role in the disease. The size of this expansion has a direct link to the aggregation proneness as well as the severity of pathological and clinical features. Aims The aim of our study is reducing mutant htt transcript and protein levels by targeting its prolonged CAG repeat in the HD gene and thereby inhibiting all downstream toxic effects. Methods Patient derived fibroblasts and lymphoblasts were used to transfect fully modified 2'O methyl phosphorothioate antisense oligonucleotides (AONs), designed to target the expanded CAG repeat in HD. Various AON concentrations and CUG lengths were applied. Htt transcript levels were measured by RT-PCR and qRT-PCR and protein levels were measured by Western blot and time resolved FRET. Results We show that an AON that recognises seven consecutive CAG trinucleotides reduces both mutant htt transcript and protein levels in patient derived cells. In the human genome there are numerous proteins that contain polyQ tracts and these are usually encoded by a combination of CAG and CAA triplets. Those CAG enclosing transcripts were found to be unaffected by the (CUG)7 AON treatment. Conclusions Here we make use of AONs targeting the CAG repeat as a therapeutic strategy to effectively reduce both htt transcript and protein levels in patient derived HD cells. Other endogenous CAG enclosing transcripts were found to be unaffected by AON treatment, making the (CUG)7 AON a promising therapeutic tool to specifically reduce mutant htt in HD.

. In our research, we include two other simpler representatives of the boroxine family compounds: trimethoxyboroxine and trimethylboroxine, which are commercially available. The study objective is to explore the possibility of similar behavior within the same class of boron compounds, that is, to examine the activity of K2[B3O3F4OH] compared to simpler representatives of the same family of compounds. On the one hand, K2[B3O3F4OH], theoretically has the ability to exchange electrons in the extinction of reactive radicals, since two boron atoms are sp3-hybridized and use electrons from the inner shell. On the other hand, trimethoxyboroxine, and trimethylboroxine, in theory, should not exchange electrons. However, recent studies indicate the potential for the boron atom to act like carbon and participate in the exchange of protons. The study used the standard laboratory method of 2,2-diphenyl-1-picrylhydrazyl (DPPH) antioxidant assay. The selected boroxines were treated with a DPPH radical at a temperature of 35° C in various concentrations, and with a reaction time of one hour. Results of the DPPH test show an extremely weak antioxidant capacity exists for all investigated boroxines. When K2[B3O3F4OH] was tested at high concentrations, instead of decreased color in the DPPH radicals, there was an increase in absorbance readings, which could mean that this compound acts as a pro-oxidant at higher concentrations. Future research is recommended to examine the length of reaction times needed, and whether a change in the reaction conditions would boost the antioxidant capacity of K2 [B3O3F4OH]. Finally, future research could test the hypothesis that K2[B3O3F4OH], in the absence of the expected antioxidant activity, acts as a pro-oxidant.UDC Classification: 615.1; DOI: http://dx