Are stem cell therapies a treatment alternative for ALS
Amyotrophic lateral sclerosis (ALS) is a rare disease which causes the degradation of motor neurons. Its cause(s) and the underlying mechanism is not yet identified and up to date no therapy exists to cure or halt the progression of ALS, ultimately causing fatal respiratory failure. Besides few medication options to prolong the life expectancy by several month, only few alternative, exploratory therapies exist, including treatments with stem cells or stem cell conditioned media. The following chapters summarise current knowledge on ALS, standard and alternative therapies, stem cells and its secretome and how they are used as therapeutic regimen in clinical trials.
What is ALS and what are potential causes?
ALS is a rare motor neuron disease whose onset usually starts between the age of 40 and 70 but in some cases can start already in the twenties. It is characterised by progressive muscular weakness caused by the degeneration of motor neurons, initially leading to muscle weakness/stiffness but ultimately causing fatal respiratory failure after approximately 3-5 years iv (Rowland & Shneider, 2001). To date there is no cure for ALS and no treatment available which can completely halt or even reverse the progression of the disease. The reason for the onset of ALS is sporadic (90-95%), which means that there is no common cause and everybody, no matter which age, sex or ethnic background can in principle develop ALS. Nevertheless, some genetic modifications have been identified which increase the chance of developing ALS and can cause familial ALS (5-10%) iii (Muzio, Viotti, & Martino, 2021).
What are the current options to treat ALS?
As there is no option to cure ALS, no standard therapy exists which is used by all physicians worldwide. The treatment is rather a personalised supportive health care with individualised treatment plans which covers different aspects of the disease vi (Sykova, Cizkova, & Kubinova, 2021):
- Nutritional Support – Prepare small meals with appropriate calorie intake
- Riluzol. It decreases glutamate levels in motor neurons and is believed to reduce overall damage. Survival is prolonged by ~ 2-3 month i(Corcia, Beltran, Bakkouche, & Couratier, 2021).
- Edaravone. Anti-Oxidant which does slow the progression of ALS.
- Different treatment of symptoms caused by ALS (against cramps, stiffness, excess saliva etc.)
- Physical Therapy – Training doesn’t stop the degradation but can train (yet) unaffected muscles which can prolong the independence of the patient.
- Breathing and Communication Support – With ongoing muscular degradation the ability to breathe and talk will be affected. Ventilation support and computer-based speech support can be applied.
What are the problems with current treatment options and what needs to be changed?
The main problem with the current treatment options is that they only treat ALS symptoms and do not effectively halt or even reverse the ongoing muscular degradation. It is therefore essential to develop therapies that are able to stop the degradation or at least prolong the survival significantly, which is usually only 3-5 years after diagnosis.
Which trustworthy alternative treatments are available to treat ALS?
No alternative treatment to cure or stop ALS-progression does exist but scientists are working on three promising alternative approaches which might be used in the future as potential therapies, if they succeedi (Corcia et al., 2021).
- It is essential to understand the reasons for the specific death of motor neurons which seems to be caused by a variety of cellular defects (protein recycling, gene regulation, structural impairments). Additionally, cells of the immune system seem to be involved (glial cells).
If the underlying mechanism is understood, a more specific drug-treatment can be developed.
- Several genes have already been identified which are risk-factors for the development of ALS. Gene-therapy approaches are being tested to modify the activity of certain genes of interest via epigenetic modification.
- Stem cell research is the third and most promising approach currently under investigation. Their use in treating ALS or other related diseases like Alzheimer might be a game changer.
What kind of stem cell alternatives are offered to treat ALS already?
Stem cells are well-known for their potential to differentiate and grow during our whole life, constantly replenishing various cell types. Those cells are mainly localized in our bone marrow but also in some other niches within our body. Since scientist revealed the potential of these immortal cells, they have been within focus for the development of certain technologies. There are two basic ideas behind using stem cells to treat ALS vi (Sykova et al., 2021):
- The substitution of the damaged tissue by injection of stem cells to the affected area. Many different clinical studies have already been filed to investigate the best route of administration (intracerebral, intrathecal, intravenous, intravascular) of certain stem cell types (e.g. mesenchymal or hematopoietic stem cells) and how often they need to be injected.
- As a supportive role to provide neuroprotection due to direct cell-cell interaction or secreted proteins and microsomes.
Initial results showed that such a transplantation could not cure ALS but prolong the overall survival time significantly. Currently there are five different clinical studies* ongoing which use stem cells to treat ALS with other treatment regimens.
What are potential risks of treating ALS with stem cells?
Stem cell isolation, their cultivation and in vitro expansion are quite complex procedures, especially if they are meant to be reinjected in vivo. On the one hand, the risk of contamination and subsequent rejection of the cells might occur. On the other hand, cells that are expanded too rapidly might loose their potency or might transform into cancer cells if treated with complex cocktails of growth factors for too long. Hence, the whole process must be strictly controlled throughout the whole life cycle of the cells, from isolation to reinjection or the therapy might cause adverse effects or be simply ineffective.
What is the stem cell secretome?
One reason for the observed beneficial effects after injection of stem cells might be the secreted compounds (cytokines or other biologically active proteins) into their so-called “microenvironment”. The entirety of these secreted compounds, which are incorporated within exosomes, is called “secretome”.
Several publications already showed that this secretome contains neuroprotective growth factors which can protect neurons and glial cells and at the same time activate anti-inflammatory and anti-apoptotic pathways within the surrounding tissue ii,v (Marconi et al., 2012; Shin et al., 2021). It is also discussed if exosomes transfer miRNA which play a key role in inter-cellular communication (Shin et al., 2021). Scientific data supports the theory that injection of stem cell conditioned media can mitigate the severity of the injury and enhance functional recovery of spinal cord injury in animal models v(Shin et al., 2021). Results from animal models for ALS showed that the use of stem cells or its secretome does have beneficial effects but it appears as if the secretome alone is sufficient, indicating that it is probably not necessary to inject the stem cells.
What is the ANOVA IRM secretome?
The secretome provided by ANOVA IRM is the most advanced alternative MSC secretome on the market. Only one donation is necessary to isolate your own personal mesenchymal stem cells which are then cultivated in vitro for a short period to generate sufficient amounts of stem cell-conditioned medium which contains the exosomes secreted by your stem cells. After separating the stem cells from the medium, your own personalized secretome will undergo a thorough internal quality control before it is being used for up to 10 treatments, which will be scheduled according to your special needs. All internal processes are controlled by German Drug Authorities and are therefore highly regulated to yield the best quality available.
What are the advantages?
There are many advantages when using the ANOVA secretome over the injection of stem cells. As the stem cells are cultivated over a short period of time and under mild conditions there is only a low risk of loss of potency during the cultivation. No cells have to be reinjected and therefore the risk for infections or the risk to develop cancer from the pluripotent stem cells does not exist. Your own personalized secretome-containing medium will be generated and stored until you need it, hence there is no need to reschedule your appointment in case the stem cells didn’t grow properly which might be the case if stem cells need to be injected. Finally, you can rely on the highly regulated system of the German Drug Authorities when it comes to quality and safety of the final product.
Whether Stem Cell Secretome is a treatment option for you depends on your current health status and the underlying problem in your specific case. If you would like to know more about your treatment options with Stem Cell Secretome, schedule an appointment today. Our doctors will assess your medical files to see if you can benefit from stem cell treatment.
References and Literature
- Corcia, P., Beltran, S., Bakkouche, S. E., & Couratier, P. (2021). Therapeutic news in ALS. Rev Neurol (Paris), 177(5), 544-549. doi:10.1016/j.neurol.2020.12.003
- Marconi, S., Castiglione, G., Turano, E., Bissolotti, G., Angiari, S., Farinazzo, A., . . . Bonetti, B. (2012). Human adipose-derived mesenchymal stem cells systemically injected promote peripheral nerve regeneration in the mouse model of sciatic crush. Tissue Eng Part A, 18(11-12), 1264-1272. doi:10.1089/ten.TEA.2011.0491
- Muzio, L., Viotti, A., & Martino, G. (2021). Microglia in Neuroinflammation and Neurodegeneration: From Understanding to Therapy. Front Neurosci, 15, 742065. doi:10.3389/fnins.2021.742065
- Rowland, L. P., & Shneider, N. A. (2001). Amyotrophic lateral sclerosis. N Engl J Med, 344(22), 1688-1700. doi:10.1056/NEJM200105313442207
- Shin, S., Lee, J., Kwon, Y., Park, K. S., Jeong, J. H., Choi, S. J., . . . Lee, C. (2021). Comparative Proteomic Analysis of the Mesenchymal Stem Cells Secretome from Adipose, Bone Marrow, Placenta and Wharton's Jelly. Int J Mol Sci, 22(2). doi:10.3390/ijms22020845
- Sykova, E., Cizkova, D., & Kubinova, S. (2021). Mesenchymal Stem Cells in Treatment of Spinal Cord Injury and Amyotrophic Lateral Sclerosis. Front Cell Dev Biol, 9, 695900. doi:10.3389/fcell.2021.695900