Treatment with human fat tissue-derived mesenchymal stem cells (MSCs) may improve motor nerve cell health and survival in infants with spinal muscular atrophy (SMA) type 1, according to data from a small Phase 1 clinical trial in Iran.
Notably, the stem cell treatment appeared to have effectively slowed disease progression in one of the five treated infants, who remained alive after four years — in contrast with the up-to-two-year life expectancy for untreated patients — and was free of invasive ventilation.
These early findings suggest this type of therapy should be tested in larger studies to better assess its potential in this patient population, the researchers noted.
The results were reported in the study “An open-label phase 1 clinical trial of the allogeneic side population adipose-derived mesenchymal stem cells in SMA type 1 patients,” published in the journal Neurological Sciences.
SMA is caused by absent or low production of SMN, a protein essential for the health of motor neurons, due to mutations in the SMN1 gene. Motor neurons are the specialized nerve cells that control voluntary movement.
SMN deficiency leads to the progressive death of motor neurons and to muscle wasting and atrophy, which mainly affects motor and lung function.
Infants with SMA type 1, the most common and second-most severe form of the disease, typically develop symptoms within the first six months of life and don’t survive past age 2 if untreated.
MSCs, which are capable of maturing into many other cell types, are gaining increasing interest as a potential therapeutic approach for a number of conditions due to their strong immunosuppressive, anti-inflammatory, neuroprotective, and regenerative properties.
As such, MSCs may have the potential to protect motor neurons and prevent their death, and thereby slow disease progression in infants with type 1 disease.
Previous, small case reports using bone marrow-derived MSCs for treating SMA type 1 patients provided inconsistent findings.
Now, researchers in Iran evaluated the safety and effectiveness of treating type 1 infants with a subpopulation of fat tissue-derived MSC — previously shown to have greater regenerative capacities — in a Phase 1 clinical trial (NCT02855112).
The single-center study, initiated in July 2015, enrolled 10 infants (less than 1 year old) with SMA type 1 and whose disease onset occurred at a mean age of 3 months. No infant had received any disease-modifying therapy for SMA previously; at the time, none had been approved in any country.
Participants were assigned randomly to receive either three intrathecal injections of fat tissue-derived MSCs per kilogram, separated by three weeks, or no intervention, in addition to supportive care.
Intrathecal injection is given directly into the spinal canal to reach the cerebrospinal fluid, which surrounds the brain and spinal cord. The subpopulation of fat-derived MSCs was obtained from volunteer donors.
The age of infants assigned to MSCs treatment ranged from 2 to 10 months at the moment of the first injection. Participants were followed for up to 48 months (about four years).
Results showed that MSC treatment was generally safe, without remarkable side effects and only two infants experiencing mild fever.
In addition, after the third injection, all treated infants showed significantly better motor/muscle responses in the tibial leg muscle relative to those who did not receive the therapy.
No significant group differences were observed in terms of motor development milestones, weight gain, hospital admissions, and number of days needing ventilation.
Notably, there was a trend for extended survival in the treated group, compared with the non-treated group (mean of 11.2 vs. 8.5 months). After four years of follow-up, one of the patients in the intervention group, who received the therapy at the oldest age (10 months) remained alive.
At latest assessment, he was more than 5 years old and unable to sit, but showed appropriate weight gain and needed non-invasive ventilation for about eight hours daily.
These early findings suggest that treatment with a subpopulation of fat tissue-derived MSCs is safe and may promote some benefit in SMA type 1 patients.
However, the results are “not definitive and no trial has been replicated in multiple centers,” the researchers wrote, adding that further research should focus on developing improved stem cell therapies and testing them in multi-center studies.