Trophos made sure that olesoxime had all the basic criteria for a clinical trial; indeed, this molecule had yielded very convincing results on motor neuron survival in several pathological setups in animal models. Unfortunately, olesoxime did not extend survival of ALS patients. As with other unsuccessful trials, this failure underlines the difficulty of treating a progressive disease with symptoms appearing in late adulthood. I have several comments on this point.

First, this result does not jeopardize the clinical trial ongoing on spinal muscular atrophy (SMA) patients: That SMA patients can be identified genetically, and that the disease is progressing much earlier and more slowly, allow for a more timely treatment.

Second, olesoxime, although ineffective in treating symptomatic patients, could still prove to be part of a combination of molecules in the future.

Nevertheless, these negative results, added to the numerous unsuccessful past trials, raise the question of the suitability of our experimental models, which are mostly murine (and this is true for almost...  Read more

Trophos made sure that olesoxime had all the basic criteria for a clinical trial; indeed, this molecule had yielded very convincing results on motor neuron survival in several pathological setups in animal models. Unfortunately, olesoxime did not extend survival of ALS patients. As with other unsuccessful trials, this failure underlines the difficulty of treating a progressive disease with symptoms appearing in late adulthood. I have several comments on this point.

First, this result does not jeopardize the clinical trial ongoing on spinal muscular atrophy (SMA) patients: That SMA patients can be identified genetically, and that the disease is progressing much earlier and more slowly, allow for a more timely treatment.

Second, olesoxime, although ineffective in treating symptomatic patients, could still prove to be part of a combination of molecules in the future.

Nevertheless, these negative results, added to the numerous unsuccessful past trials, raise the question of the suitability of our experimental models, which are mostly murine (and this is true for almost all trials).

Perhaps we should look into new tools such as induced pluripotent stem cells taken from ALS patients and derived into motor neurons. They could generate more pertinent models. These results also emphasize the continuous necessity for basic research support, in particular, to fund programs aimed at understanding the origin and first triggers of the disease. Indeed, finding ways of blocking such early triggers, combined with serious epidemiological studies to determine whether some populations are more at risk for disease because of environmental or other reasons, could ultimately lead to the development of preventive treatments. Although this negative result has certainly been disappointing to both patients and Trophos, the key for success is in basic and clinical researchers continuing to work together with companies such as Trophos. One day it will work!

View all comments by Brigitte Pettmann

I would wonder whether addressing mitochondrial function, one of the earliest events in ALS (presymptomatic), would be overwhelmed by other factors driving disease once symptomatic and, hence, diagnosable with current methods. I am in the camp of neuroinflammation driving progression, and still think olesoxime and/or dexpramipexole (which I also suspect might suffer the same issue as olesoxime did) can be valuable ingredients of a cocktail-style treatment plan that addresses the inflammatory component as well.

View all comments by Eric Valor