Abstract
Background aims
Thanks to their immunomodulatory, tissue-protective and regenerative properties, mesenchymal
stromal cells (MSCs) are a promising approach for amyotrophic lateral sclerosis (ALS);
however, trials are limited and few follow-up studies have been published. This post-hoc
analysis aims to describe the potential long-term effects of MSCs in ALS, analyzing
data from two phase 1 clinical trials in ALS patients conducted by our group in 2002
and 2006.
Methods
We conducted two consecutive phase 1 prospective, open, pilot clinical trials, enrolling
a total of 19 ALS patients. We followed patients for the duration of the disease.
For each patient, we used the European Network to Cure ALS (ENCALS) survival prediction
model to retrospectively calculate the expected survival at diagnosis. We then compared
the predicted disease duration with the observed survival, analyzing patients at a
single-patient level.
Results
Using the ENCALS model, we predicted short survival in one patient, intermediate survival
in three patients, long survival in three patients and very long survival in 12 patients.
The difference between predicted and observed survival for the whole group was significant
and demonstrated a mean predicted survival of 70.79 months (standard deviation [SD],
27.53) and a mean observed survival of 118.8 months (SD, 89.26) (P = 0.016). Based on the monthly ALS Functional Rating Scale–Revised progression rate
(median, 0.64/month), we considered 10 of 19 patients slow progressors and nine of
19 patients fast progressors. Of the slow progressors, eight of 10 (80%) had significantly
increased disease duration compared with predicted, and only two (20%) had decreased
estimated disease duration. By contrast, five of nine (55%) fast progressors had increased
disease duration, whereas four (45%) had decreased disease duration. To date, four
patients are still alive.
Conclusions
The current study represents the first very long-term analysis of survival as an effect
of MSC focal transplantation in the central nervous system of ALS patients, demonstrating
that MSC transplantation could potentially slow down ALS progression and improve survival.
Due to the interindividual variability in clinical course, at the current state of
our knowledge, we cannot generalize the results, but these data provide new insights
for planning the next generation of efficacy MSC clinical trials in ALS.
Key Words
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Article info
Publication history
Published online: March 15, 2023
Accepted:
February 13,
2023
Received:
December 2,
2022
Publication stage
In Press Corrected ProofIdentification
Copyright
© 2023 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.
