Research Review No. 88.
Recent exciting new Developments; 2015-1
A general oveview.
The Studies:
1.
Fox, D.J., Kumar, A., West, N.A., DiRienzo, A.G., James, K.A. & Joyce
Oleszek, J. (2015) Trends With Corticosteroid Use in Males With Duchenne
Muscular Dystrophy Born 1982-2001. Journal of Child Neurology. 30(1) 21-26.
Comment:
The authors from U.S.A. surveyed 521 firstborn males with Duchenne
Muscular Dystrophy (DMD). They compared males born between 1982 and 1986
with males born between 1997 and 2001. During those years, steroid use
increased from 54% to 72%, while the mean age at steroid initiation decreased
from 8.2 to 7.1 years. They found that Hispanic and non-Hispanic black males
used steroids less frequently and delayed initiation compared to white males.
They urge that such studies should be repeated with males born after 2001 and
that these disparities should be taken into consideration when steroid therapy is
undertaken.
2.
O'Donovan, L., Okamoto, I., Arzumanov, A.A., Williams, D.L., Deuss, P. &
Gait, M.J. (2015) Parallel Synthesis of Cell-Penetrating Peptide Conjugates of
PMO Toward Exon Skipping Enhancement in Duchenne Muscular Dystrophy.
Nucleic Acid Therapeutics. 25(1):1-10.
Comment:
In this study from the U.K., the authors developed methods of increasing
the rate at which phosphorodiamidatemorpholino oligonucleotides (PMO) can be
applied to the search for exon-skipping optimization of peptide sequences in
conjugates of PMO for therapeutic screening.
3.
Ousterout, D.G., Kabadi, A.M., Thakore, P.I., Perez-Pinera, P., Brown,
M.T., Majoros, W.H., Reddy, T.E. & Gersbach, C.A. (2015) Correction of
dystrophin expression in cells from duchenne muscular dystrophy patients
through genomic excision of exon 51 by zinc finger nucleases. Molecular
therapy: the journal of the American Society of Gene Therapy. 23(3):523-532.
Comment:
This study from U.S.A. applies studies for the engineering of site-specific
nucleases (DNA affecting enzymes), which can perform changes in the DNA of
complex genomes. They use the term ‘designer enzymes’ for the group of
enzymes with in which they are particularly interested, so-called zinc finger
nucleases (ZFNs). ZFNs are targetable DNA cleavage reagents that have been
adopted as gene-targeting tools. ZFN-induced double-strand breaks are subject
to cellular DNA repair processes that lead to both targeted mutagenesis and
targeted gene replacement at remarkably high frequencies. In this study the
authors demonstrate that a clonally derived, genetically corrected population of
DMD patient cells using ZFN technology can generate human dystrophin
expression in cells, such that it is properly localized to the sarcolemma
membrane. They consider that this type of “gene correction by excising exons
from the genome may be a viable method for creating an autologous population
of corrected cells.”
Karl A. Bettelheim
21.3.2015