Pleased to share this first-author review, out now in Molecular Neurodegeneration! 'The era of cryptic exons: implications for ALS-FTD' We discuss recent discoveries & the exciting opportunities that cryptic exons offer for the development of novel therapies & biomarkers in #ALS #MND #FTD 🧠🧪

Boosting muscle BDNF rescues impaired in vivo axonal transport of signalling endosomes in CMT2D mice: insight.jci.org/articles/view/… UCL Queen Square Institute of Neurology UCL Brain Sciences UK Dementia Research Institute #AxonalTransport #CMT #MotorNeuron #NMJ #PeripheralNerve CMT United Kingdom HereditaryNeuropathy CMT Research Foundation Muscular Dystrophy UK TREAT-NMD

Well done anna-leigh!! AL Brown

We are recruiting a lab manager! If interested in helping shape a growing lab and directly contribute to molecular and cellular translational research in ALS, in London, please apply below: ucl.ac.uk/work-at-ucl/se…

Check out our new preprint on generation and characterisation of C9orf72 polyGR and polyPR knock-in mice. A huge effort over many years by Carmelo Milioto and many collaborators incl. Marc Aurel Busche Soyon Hong biorxiv.org/cgi/content/sh… 1/5

Our latest Neuron reveals widespread mislocalisation of proteins & mRNAs in ALS. This is partly reversed by VCP ATPase inhibition: cell.com/neuron/pdfExte… UCL Queen Square Institute of Neurology MND Association Medical Research Council The Lister Institute of Preventive Medicine Oliver Ziff Jasmine Harley @erist_yiran Jacob Neeves PataniLab The Crick

Want to deliver gene therapies broadly, but activate them only in diseased neurons? TDP-REG "hacks" TDP cryptic mis-splicing to drive expression only WHEN and WHERE needed! Less toxicity, wider therapeutic window, new options for sporadic ALS therapies. biorxiv.org/content/10.110…

See the full thread from brilliant first author Oscar Wilkins Exceptional collaborators on this, including Claire Le Pichon ule_lab Max Z. Y. J. Chien Jo Wlaschin UCL Queen Square Institute of Neurology The Crick

Really excited about our latest preprint, where we uncovered a neuroprotective role for neuronal polyunsaturated fatty acids in FTD and ALS. Led by Ashling Giblin and Alex Cammack biorxiv.org/cgi/content/sh… 1/9

TDP-43 loss causes mis-splicing in ALS/FTD. We now show it also induces widespread cryptic 3'UTRs. This increases RNA stability, translation and function of ELK1 and other TFs. Also provides novel targets for biomarker and therapeutics development. biorxiv.org/content/10.110…

This work was led by Sam Bryce-Smith and a joint effort with Maria Secrier and many others. Parallel efforts from the Gitler and La Spada labs also identify the link between TDP-43 and 3'UTR changes and out now: biorxiv.org/content/10.110… biorxiv.org/content/10.110…

Do you love #RNA and #neuroscience? Are you looking for a #postdocposition on #ALS and gene therapy? Join Ruepp Lab UK Dementia Research Institute Institute of Psychiatry, Psychology & Neuroscience and FrattaLab UCL Queen Square Institute of Neurology for a collaborative pre-clinical project on a novel gene therapy approach for ALS. More info here: tinyurl.com/2cpcbsp3

Why small mindedness is having big consequences Brain I live under its shadow. I suspect most of you do too. It is the great mountain of small things. The higher it gets, the bigger the shadow it casts: a malignant darkness that pervades our lives. academic.oup.com/brain/article/…

We're looking for someone with a creative mindset and excellent modern molecular biology skills (DNA manipulation, Illumina, Nanopore etc) to join our team at UCL and The Crick in the FrattaLab developing candidate gene therapies for ALS. Apply here: jobs.ac.uk/job/DGJ551/res…

New postdoc opportunity to work on splicing and ALS therapeutics The Crick and UCL Queen Square Institute of Neurology. Basic molecular work with true translational potential. 4 days still to apply. jobs.ac.uk/job/DGJ551/res…

Age-dependent and compartment-specific changes in mitochondrial homeostasis & cytoplasmic biophysics in ageing PNS neurons: onlinelibrary.wiley.com/doi/10.1111/ac… Big Aging Cell study & effort from Alessio Vagnoni UCL Queen Square Institute of Neurology Francesca Mattedi Sandy Richter Emily The MNP Lab #Ageing

We find TDP-43 loss to cause presynaptic defects, which are rescued by ASOs correcting a single cryptic exon in UNC13A. Surprising effect of just one cryptic exon and promising strategy for ALS! Matt Keuss Pete Harley in great collaboration with Juan Burrone Lab biorxiv.org/content/10.110…

Very nice work combining strategies for AAV targeting to muscle from Annalucia Darbey of the FrattaLab: biorxiv.org/content/10.110… UCL Queen Square Institute of Neurology UCL Brain Sciences The Crick UCL Div of Surgery UK Dementia Research Institute