ALS Stem Cell Treatment

Using Stem Cell Therapy for Amyotrophic Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) is caused by the progressive death of cerebral (upper) and spinal (lower) motor neurons. It is a complex disease which involves the activation of several cellular pathways in both neurons and glial cells (Figure 1). This results in a severe motor dysfunction muscles become atrophic due to the lack of nerve stimulation. Often, the origin of the disease is unknown. ALS is not a typical autoimmune disorder, since autoimmune and inflammatory abnormalities are not the cause of the disease, even though they influence its progression.

The therapeutic strategy used for treating ALS is aimed at protecting neurons from degeneration, and to stimulate cell regeneration. However, currently there is no drug treatment that can restore neural cells.

Stem Cell-based therapies may be the answer. A study by Mazzini et al. demonstrated that the procedure of ex vivo expansion of autologous Mesenchymal Stem Cells (MSCs) and transplantation into the spinal cord of humans was safe and well tolerated by ALS patients. A more recent study, by the same group, however, confirmed that MSC transplantation into the spinal cord of ALS patients is not only safe, but might also serve as a treatment option for future cell-based clinical trials for the treatment of ALS (Figure 1).

Many current preclinical studies suggest that stem cell transplantation has the best effect when aimed towards protecting, rather than replacing or repairing the motor neurons of ALS patients.

Our experience shows that Stem Cell Secretome is a promising, novel strategy that appears to be more effective and safer than the cells themselves. Stem Cell Secretome is the essence of stem cells, and can facilitate neuroprotection and recovery of neuromotorial function. ANOVA offers this experimental and novel stem cell-based therapy patients with ALS. For more information, please feel free to contact us.

Understanding ALS on a Cellular Level

Stem Cell ALS 10Figure 1: shows the complexity of ALS, which involves many different pathways in motor neurons and neighboring glia. Microglia (bottom part) activate an inflammatory cascade via MCP-1 secretion. Astrocytes (purple cells) contribute to the injury of motor neurons through various mechanisms, including release of inflammatory mediators such as NO and PGE2 (left), reduced expression and activity of the glutamate transporter (right), reduced lactate release (top left) and activation of pro-NGF–p75 receptor signaling (left). Motor neurons also undergo abnormal RNA processing which, together with overproduction of reactive oxygen species (ROS), contribute to protein misfolding (center). Misfolded proteins can form aggregates, leading to cellular stress and ultimately activate autophagy and apoptotic pathways. Two major components of motor neuron injury are mitochondrial impairment and dysregulation of calcium handling (top middle) which also stimulate the apoptotic cascade. Impaired axonal transport (left bottom) may contribute to an energy deficit, disturbing normal functionality (distal axonopathy). Abbreviations: EAAT2, excitatory amino acid transporter 2; ER, endoplasmic reticulum; IL, interleukin; MCP-1, monocyte chemoattractant protein 1; NGF, nerve growth factor; NO, nitric oxide; PGE2, prostaglandin E2.

Stem Cell Secretome Therapy for ALS

Several clinical trials with stem cells for ALS are ongoing. As usual during studies, new insights emerge. The ANOVA Stem Cell Secretome is the product of the latest insights to what actually causes the stem cell therapies to be effective. Stem Cell Secretome for ALS employs mesenchymal stem cells (MSC) secretome for a variety of reasons.
As explained in detail in our Information for Professionals section, MSCs can secrete many trophic and neuroprotective factors. Additionally, among the micro vesicles secreted from the MSC, are the very important exosomes transporting microRNAs (miR-29a, miR-9, miR-124, miR-145). It is known that the exposure of neurons and astrocytes with MSC secreted exosomes leads to an increase of miR-133b which was shown to promote functional neurological recovery.
The ANOVA Stem Cell Secretome  harnesses these and many other factors in a high concentration.
It is important to note that novel therapies such as stem cell-based therapies have not undergone the full clinical evaluation yet. Therefore, the attending physician must assess the risks and benefits associated with stem cell therapy for each patient individually. If the benefits outweigh the potential risks, the doctor may suggest experimental therapies to the patient.

This treatment may significantly be enhanced by a therapeutic combination with Infusion Therapy. If you are interested to learn more about the combination therapy, click “I am interested in Infusion Therapy” on our Contact Page.
References and Literature - Stem Cell-based Therapies and Amyotrophic Lateral Sclerosis (Click for more)

  1. Wijesekera, Lokesh C., and P. Nigel Leigh. "Amyotrophic lateral sclerosis." Orphanet journal of rare diseases 4.1 (2009): 3.
  2. Ferraiuolo, Laura, et al. "Molecular pathways of motor neuron injury in amyotrophic lateral sclerosis." Nature Reviews Neurology 7.11 (2011): 616-630.
  3. Mazzini, Letizia, et al. "Stem cell therapy in amyotrophic lateral sclerosis: a methodological approach in humans." Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders 4.3 (2003): 158-161.
  4. Mazzini, L., et al. "Mesenchymal stem cell transplantation in amyotrophic lateral sclerosis: A Phase I clinical trial." Experimental neurology 223.1 (2010): 229-237.
  5. Papadeas, Sophia T., and Nicholas J. Maragakis. "Advances in stem cell research for Amyotrophic Lateral Sclerosis." Current opinion in Biotechnology 20.5 (2009): 545-551.
  6. Janson, C. G., et al. "Human intrathecal transplantation of peripheral blood stem cells in amyotrophic lateral sclerosis." Journal of hematotherapy & stem cell research 10.6 (2001): 913-915.
  7. Thomsen, Gretchen M., et al. "The past, present and future of stem cell clinical trials for ALS." Experimental neurology 262 (2014): 127-137
  8. Staff, Nathan P., et al. "Safety of intrathecal autologous adipose-derived mesenchymal stromal cells in patients with ALS." Neurology 87.21 (2016): 2230-2234.
  9. Oh, Ki-Wook, et al. "Phase I Trial of Repeated Intrathecal Autologous Bone Marrow Derived Mesenchymal Stromal Cells in Amyotrophic Lateral Sclerosis." Stem cells translational medicine 4.6 (2015): 590-597.
  10. Petrou, Panayiota, et al. "Safety and clinical effects of mesenchymal stem cells secreting neurotrophic factor transplantation in patients with amyotrophic lateral sclerosis: results of phase 1/2 and 2a clinical trials." JAMA neurology 73.3 (2016): 337-344.
  11. Farinazzo, Alessia, et al. "Murine adipose-derived mesenchymal stromal cell vesicles: in vitro clues for neuroprotective and neuroregenerative approaches." Cytotherapy 17.5 (2015): 571-578.
  12. Bonafede, Roberta, et al. "Exosome derived from murine adipose-derived stromal cells: Neuroprotective effect on in vitro model of amyotrophic lateral sclerosis." Experimental cell research 340.1 (2016): 150-158.
  13. Boruczkowski, D., et al. "Mesenchymal Stem Cells As A Therapeutic Option For Patients With ALS." Gen Med (Los Angel) 4.235 (2016): 2.


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