Reacción a ""Promising" new strategy for ALS using stem cells created from patients"

The study is of very good quality and is backed by data that can be replicated... although I don't know if this is sufficiently robust.

This is a very specific study, conducted in a cell model derived from patients (IPSCs), and we all know that these models are not very reproducible. This does not invalidate it, but we must consider that its reproducibility is in question in view of further investigation of the results.

In principle, it fits quite well with the existing evidence. It offers relatively novel data on the functionality of a protein encoded by the VCP gene. This gene gives rise to a very low percentage of familial ALS cases that are specifically limited to Brazil and other Portuguese-speaking countries (some families have been described in Mozambique). Around 0.01-0.05% of ALS patients (or even lower).

However, the data it provides on how the interaction process between the endoplasmic reticulum and mitochondria is altered offers new insights into a weak point in motor neurons, which could somehow lead to their degeneration and the neurodegenerative process in ALS. And, therefore, how the Integrated Stress Response (ISR) mechanism is altered in this type of neurodegeneration.

All of this provides new ideas for exploring novel avenues that may lead to the development of plausible therapies in the rather distant future. These therapies will undoubtedly be dedicated to a very specific subgroup of patients.

[On its limitations]

The results of the study are confusing in themselves. On the one hand, because the model used is not very reproducible and, above all, because the results are apparently promising, and the only thing they would demonstrate (if everything is proven to be reproducible in the long term and in other in vivo models) is a new pathway for the initiation and development of the neurodegenerative process in ALS.

[On the implications for the real world, for clinical practice]

At present, none. Looking ahead to the future, which is unfortunately still far off, it may be possible to test some types of therapies targeting this new mechanism supposedly associated with ALS, which could probably (always in the conditional, as these are future hypotheses) yield results in very specific and small subgroups of patients.