Potential novel therapy for ALS An antisense oligonucleotide which inhibits formation of toxic protein aggregates in the central nervous system of an ALS mouse model provides hope for a new widely applicable therapy for the disease BETHAN CRITCHLEY Amyotrophic lateral sclerosis ALS is a fatal adult onset neuromuscular disorder characterised by progressive loss of bulbar and or spinal motor neurons which leads to muscle weakness twitching and cramping The cause is not well understood yet 97 of ALS patients have aggregates of TDP 43 present in their central nervous system CNS making the protein an ideal target for ALS therapies TDP 43 is an RNA binding protein which is involved in the process of gene expression and regulation therefore direct silencing of TDP 43 is unlikely to be an appropriate option as evidenced by the current lack of TDP 43 directed ALS therapies Becker et al 1 investigate a novel therapeutic strategy which indirectly reduces levels of TDP 43 by lowering levels of ataxin 2 using an antisense oligonucleotide ASO Mutations in the ataxin 2 gene are not directly linked to ALS however an earlier study by the same group2 identified that the gene is associated with ALS susceptibility indicating that the interaction between ataxin 2 and TDP 43 may be a candidate for therapeutic intervention In the present study
