FrattaLab (@FrattaLab) / X

Out @ScienceMagazine! New tech to activate ALS gene therapies only in the right cells at the right time - Increased safety to have more options for ALS. We do it by taking advantage of cryptic splicing. science.org/doi/10.1126/sc… @UCLIoN @TheCrick @OscarWilkins16 @MaxZYJChien

science.org

Creation of de novo cryptic splicing for ALS and FTD precision medicine

Loss of function of the RNA-binding protein TDP-43 (TDP-LOF) is a hallmark of amyotrophic lateral sclerosis (ALS) and other neurodegenerative disorders. Here we describe TDP-REG, which exploits the...

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 @PeteHarley95 in great collaboration with @jbneuro

biorxiv.org

Loss of TDP-43 induces synaptic dysfunction that is rescued by UNC13A splice-switching ASOs

TDP-43 loss of function induces multiple splicing changes, including a cryptic exon in the amyotrophic lateral sclerosis and fronto-temporal lobar degeneration risk gene UNC13A , leading to nonsens...

New postdoc opportunity to work on splicing and ALS therapeutics @TheCrick and @UCLIoN. Basic molecular work with true translational potential. 4 days still to apply. jobs.ac.uk/job/DGJ551/res…

FrattaLab

@FrattaLab

Jan 24, 2024

This work was led by @SamBryce_Smith and a joint effort with @mariasecrier 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…

biorxiv.org

TDP-43 nuclear loss in FTD/ALS causes widespread alternative polyadenylation changes

In frontotemporal dementia and amyotrophic lateral sclerosis, the RNA-binding protein TDP-43 is depleted from the nucleus. TDP-43 loss leads to cryptic exon inclusion but a role in other RNA proces...

FrattaLab

@FrattaLab

Jan 24, 2024

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

TDP-43 loss induces extensive cryptic polyadenylation in ALS/FTD

Nuclear depletion and cytoplasmic aggregation of the RNA-binding protein TDP-43 is the hallmark of ALS, occurring in over 97% of cases. A key consequence of TDP-43 nuclear loss is the de-repression...