seems like maybe universities should have organized a collective response to the assault on new college rather than just shrugging and hoping it wouldn't happen to them.

This has been a real team effort with all the coauthors! Special thanks to the SMA Foundation and SMAEurope for their advice and encouragement and F. Hoffmann–La Roche for supporting this study with an exploratory research grant Roche-Genentech.

The real heroes of this study are our participants. Even though they knew this was only a temporary implant, they stopped their lives, moved to Pittsburgh and worked with us for a couple of months! I am so glad that I had the chance to meet them. Thank you so much!

This is the first step to develop a SCS therapy for SMA that could work synergistically with the existing SMN inducing therapies to improve the quality of life of people living with SMA. Roche and Genentech: Let’s make this happen!

A follow-up controlled clinical trial is necessary to assess if the size and consistency of these beneficial effects will be sustained over long-term use of SCS.

Together these results show that SCS can reverse motoneuron dysfunction (i.e hyperexcitability and low firing rates) in a neurodegenerative disease and improve motor function.

Moreover, consistent with an increase in motoneurons firing rate, we found, using spinal cord fMRI, that spinal circuits were more active during a knee extension task post than pre-study.

But how are these large improvements possible in only 4 weeks of SCS? With @Lu_borda5, we detected post-study motoneurons with much higher peak firing rate than all pre-study motoneurons. We named them rescued motoneurons.

But not only this, SCS also improved fatigue in all participants! In a clinical test of fatigue where participants have to walk as far as they can for 6 minutes, we found improvements that were completely different from the results obtained with only exercise!

See this pretty cool video!

Then we tested whether these improvements in strength could have any translation in daily life activities like walking. Again, we found immediate and long-term improvements in gait quality variables such as stride length (SL), stride height (SH) and stride velocity (SV).

Our results are completely different to the results obtained in the only single-blind randomized clinical trial testing the effect of exercise in muscle strength in the same SMA population.

Then one day that I will always remember, we noticed that the maximum force of SMA01 was improving every day even without SCS! Actually, we found long-term improvements in all participants (up to +180%)

We found that with SCS ON, our participants could produce higher forces in some but not all single joint movements at the hip and knee.

Using biophysics to simulate SCS in SMA, we found that: 1) SCS could immediately increase motoneuron firing rate and 2) The potential effects of reverting motoneuron dysfunction could be a game changer for people living with SMA.

We wanted to test whether: 1) SCS can immediately increase motoneuron firing rate and 2) SCS can, in the long term, revert motoneuron dysfunction.

Marco and others showed that SCS can recruit sensory afferent thereby increasing sensory synaptic input to motoneurons. So we just gave it a try! We recruited 3 adults living with SMA and we stimulated them for 4 weeks.

A few years ago, our good friend, twitterless and collaborator George Mentis showed that, in SMA, motoneuron dysfunction precedes motoneuron death and is triggered by a reduction of synaptic input from sensory afferents. Fletcher 2017 www.nature.com/articles/nn....

Specifically, we report that epidural Spinal Cord Stimulation (SCS) can improve motoneuron function ( reduce hyperexcitability and increase firing rates) and motor deficits in humans with Spinal Muscular Atrophy (SMA).

We did it with Scott Ensel Serena Donadio, Robert M. Friedlander, Elvira Pirondini, @mcapo.bsky.social and others!

Hello BlueSky world! This might sound crazy but today we publish in @natureMedicine a paper showing that neurostimulation can revert motoneuron dysfunction produced by a neurodegenerative disease!
www.nature.com/articles/s41...

New results! Led by @jbarbosa.org It's not just that neurons are spiking, it is the geometry of their patterns of spiking.
Quantifying Differences in Neural Population Activity With Shape Metrics
www.biorxiv.org/content/10.1...