Stem Cell Transplantation Shows Potential as ALS Therapy, Study Suggests

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by Alice Melão |

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MSCs transplantation

Stem cell transplantation in patients with amyotrophic lateral sclerosis (ALS) has the potential to be “an important alternative strategy” in treating the disease, a new study suggests.

In recent decades, many advances in identifying and understanding the underlying mechanisms of ALS have been made. But those advances have not resulted in more or better therapies available to stop the disease commonly referred to as Lou Gehrig’s disease.

The study, titled “The use of mesenchymal stem cells (MSCs) for amyotrophic lateral sclerosis (ALS) therapy – a perspective on cell biological mechanisms” and published in Reviews in the Neurosciences, provides an overview of the therapeutic potential of stem cell transplantation as therapy for ALS. It was authored by Bor Luen Tang, associate professor in the Yong Loo Lin School of Medicine, National University Health System, Singapore.

Several potential therapeutic agents and disease modifiers have been tested in preclinical studies using animal models, and some have reached human trials. However, many fail to meet safety or efficacy requirements, with no real breakthroughs on the horizon.

In the past 20 years, only two disease-modifying drugs have been approved by the U.S. Food and Drug Administration (FDA), Sanofi’s Rilutek (riluzole) and MT Pharma America’s Radicava (edaravone).

Stem cell transplantation represents a new therapeutic approach. By transplanting multipotent mesenchymal stromal cells or mesenchymal stem cells (MSCs), it would be possible to replace degenerating or dysfunctional neurons. This approach could provide a way to overcome the main hallmarks of ALS, potentially improving patients’ symptoms and stopping disease progression.

MSCs can be isolated and expanded from several neonatal and adult sources, including umbilical cord blood, bone marrow, adipose tissue, and dental tissue. Importantly, these cells can be genetically manipulated to enhance their ALS-targeted therapeutic activities.

“MSCs could be an easily obtained and manipulated autologous source platform upon which combinatorial therapeutics could be built,” Tang wrote.

Stem cells have a great capacity to produce several signaling molecules that can modulate their surrounding environment. If stem cells could be manipulated to send anti-inflammatory and pro-survival signals, they could potentially prevent neuron degeneration and death seen in ALS.

“While replacement therapy remained unrealistic, the clinical efficacy of this therapeutic option could be potentially enhanced if we could better decipher the mechanisms underlying some of the beneficial effects of transplanted cells, and work toward augmenting or combining these in a strategic manner,” Tang wrote.

So far, preclinical studies with animal models of ALS have demonstrated the beneficial effects of MSCs transplantation, which improved motor function and prolonged the animals’ lifespan.

More recently, Phase 1 clinical trials have demonstrated the safety of several MSC delivery routes, providing support for further developments into stem cell treatment.

“The recent indication (albeit modest and limited) of procedural safety within typical disease duration and the moderate beneficial effect of MSC transplantation into patients with ALS should provide sufficient impetus for larger Phase 2b-3 trials,” the researcher wrote.

Preliminary results of Phase 2 trials suggest that that stem cell transplantation can have therapeutic potential for ALS. Although the results were not striking, some improvements on patients’ respiratory capacity and reduction of disease progression rates, compared to control groups, were reported.

“It is clear from the discouraging results of drug trials and other recent advances that merely targeting the intrinsic survivability of motor neurons would be ineffective,” Tang wrote. “Therefore, exploring the ability of MSCs (or engineered MSCs) to work on modifying the disease environment would be an important alternative strategy.”