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FrattaLab

@FrattaLab

FrattaLab @UCLIoN working on #RNA biology of #ALS and #SBMA and #Kennedy's disease
frattalab.org Joined November 2019
200 Following 960 Followers 76 Posts

Latest posts 5

FrattaLab @FrattaLab
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
www.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...
5 replies 29 reposts 101 likes 28K views View on X
FrattaLab @FrattaLab
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/content/10.110…
www.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...
3 replies 29 reposts 96 likes 13K views View on X
FrattaLab @FrattaLab
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…
www.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...
0 replies 8 reposts 25 likes 1.8K views View on X
FrattaLab @FrattaLab
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…
www.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...