Early findings show potential benefits

By Heidi Moawad, MD 

 Medically reviewed by Smita Patel, DO

Amyotrophic lateral sclerosis (ALS) can be treated with certain medications approved by the Food and Drug Administration (FDA), but the condition is not curable. However, these prescription therapies may reduce motor neuron damage, which is the cause of ALS.

Management of symptoms is the cornerstone of ALS treatment. Stem cell therapy is one of the treatment options currently being examined in research studies as a potential treatment for ALS. Stem cells are special immature cells that have the potential to develop into different kinds of cells.

The aim of stem cell therapy for ALS is to reduce motor neuron damage by using stem cells to modify the action of the immune system or by using stem cells to replace certain nerve cells.

This article will describe the stem cell therapies being investigated as potential treatments for amyotrophic lateral sclerosis.

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The Challenges of Treating and Curing ALS

So far, researchers have not been able to produce a medication or intervention that can reverse the damage of ALS. 

Many challenges must be overcome to develop treatment:

• The degeneration of motor neurons in the spinal cord causes this condition. Motor neurons do not normally regenerate if they are damaged.1

• It is not possible to screen or predict in advance whether a person will develop ALS.

• Currently, there is no way to prevent the disease from developing. 

The approved therapies have only been developed within the past few years, and research for methods of treating this disease are ongoing.

Current Treatment Options

The treatments that are currently used for ALS, Radicava (edaravone), Rilutek (riluzole), and Relyvrio (sodium phenylbutyrate and taurursodiol) work by reducing the damage to the motor neurons in the spinal cord by preventing the biological process that causes cell damage.2

These treatments have been shown to decrease inflammation and destruction of motor neurons based on microscopic evidence. For some people with ALS, the therapies may have small benefits in neurological functioning and may prolong survival by a few months.2

What Is Stem Cell Therapy?

Stem cell therapy is a type of intervention that involves the injection of stem cells into the body. This treatment is used to provide the body with new cells that have the potential to develop into mature cells that can have a healthier function than certain harmful cells in the body.

Stem cell therapy often involves a preparation process during which unhealthy cells are destroyed with medication before the new stem cells are injected into the body.3

One of the most common uses of stem cell therapy is to replace immune cells that are unhealthy and damaging to the body. One of the ways that stem cells are used in ALS research is to replace the body’s immune cells with stem cells.

It has been suggested that an alteration in immune cell function may be the cause of damage to the motor neurons in the spinal cord.4 This damage causes the irreversible symptoms of ALS.

Another way that stem cells are used in ALS research is to use stem cells to preserve astrocytes, which are a type of nerve cell.5 

How Scientists Use Stem Cells to Understand ALS

There are several ways that scientists use stem cells in ALS research. Some studies are done in a laboratory setting or with animal tissue. Very few studies have been done using stem cell therapy in humans who have ALS.

The research can give scientists information about how nerve cells respond to stem cells and whether stem cells can be used to protect nerve cells or as precursors to nerve cells that could potentially replace motor neurons in ALS.

Determine Its Causes

One of the ways that researchers use stem cells is to examine the molecular causes and potential triggers that may cause a person to develop ALS. Research is used to help scientists understand the different effects the immune system has on motor neurons, and which types of nerve tissue are impacted in ALS.

Upgrade Diagnostic Tools

Studies using stem cell therapy in tissue samples can help researchers understand whether early signs that may occur when there are changes in motor neurons can be detected with minimally invasive testing, such as blood tests or nerve conduction studies.

Develop New Treatments

Stem cell research can also help determine whether there are ways to use a person’s stem cells or donor stem cells to protect motor neurons or replace motor neurons in the spinal cord. However, the techniques can vary, and extensive research is needed to identify which techniques can help treat ALS.

Participating in Clinical Trials for ALS Stem Cell Treatments

If you are interested in participating in a clinical trial for ALS, you can discuss your interest with your healthcare providers. Depending on the progression of your disease, whether you have a family history, and what other treatments you already had, you may qualify for one or more types of clinical research trials currently underway for people with ALS.

New Breakthroughs in ALS Stem Cell Treatments

Stem cell therapy is still considered experimental in ALS. Trials are designed to examine whether the treatment is feasible, safe, and effective.

So far, studies suggest that stem cell therapy is feasible, which means that it is possible to use stem cells and inject them into people who have ALS.5 Safety is also beginning to be established, as early trials are not showing concerning adverse effects.3

The current challenge is that the effectiveness of stem cell therapy for the treatment of ALS has not been well-established. There are several ongoing research studies involving participants who have ALS.

These studies use outcomes to measure an individual's neurological functions in the short term, which can evaluate whether there is any impact on slowing disease progression.3 As the studies continue, researchers look for evidence of improved survival and a lasting effect on slowing disease progression.

Several stem cell studies have shown promise in ALS:

• In a clinical trial using autologous hematopoietic stem cell transplantation for people with ALS, the procedure was well tolerated, but there was no evidence of a significant modification in disease progression.3 In this procedure, blood-forming stem cells from a person are harvested from their blood or bone marrow and returned after the person has received treatment to stop bone marrow blood-producing activity.

• One study used human neural progenitor cells (which can form nervous system cells) modified with glial cell line-derived neurotrophic factor (GDNF), which protects astrocytes. The stem cells were injected into the participants’ lower spinal cord. At one year, there was no negative effect. Of the 18 participants, 13 participants died of disease progression. A tissue analysis of these participants showed graft survival and GDNF production, which is considered a good outcome.5

• Bosutinib, a pluripotent stem cell (iPSC)-based drug used to treat blood cell cancer, is being evaluated as a possible treatment for ALS. In one study, participants with ALS who received the drug showed a decrease in markers of ALS damage, which were measured with blood tests.6

Several things have not been established, including how long the effects of stem cell treatment might last and whether there are ALS stages when the treatment can or cannot be used.

Summary

ALS is a neurodegenerative condition that occurs when motor neurons in the spinal cord degenerate. This condition worsens rapidly after the initial symptoms. Current treatments may help prolong survival and improve quality of life.

Stem cell therapy includes experimental therapies being investigated as a potential treatment for ALS. Stem cells used for ALS may replace immune cells to prevent an immune attack on the motor neurons. Or, they may help preserve astrocytes, a type of supportive nerve cell.

Currently, the research involving stem cell therapy for the treatment of ALS suggests that it may be feasible and not harmful. However, the benefits are still yet to be determined.

 Sources

National Cancer Institute. Nerve tissue.

Jiang J, Wang Y, Deng M. New developments and opportunities in drugs being trialed for amyotrophic lateral sclerosis from 2020 to 2022. Front Pharmacol. 2022;13:1054006. doi:10.3389/fphar.2022.1054006

Lunetta C, Lizio A, Cabona C, et al. A phase I/IIa clinical trial of autologous hematopoietic stem cell transplantation in amyotrophic lateral sclerosis. J Neurol. 2022;269(10):5337-5346. doi:10.1007/s00415-022-11185-w

Leis AA, Ross MA, Verheijde JL, Leis JF. Immunoablation and stem cell transplantation in amyotrophic lateral sclerosis: the ultimate test for the autoimmune pathogenesis hypothesis. Front Neurol. 2016;7:12. doi:10.3389/fneur.2016.00012

Baloh RH, Johnson JP, Avalos P, et al. Transplantation of human neural progenitor cells secreting GDNF into the spinal cord of patients with ALS: a phase 1/2a trial. Nat Med. 2022;28(9):1813-1822. doi:10.1038/s41591-022-01956-3

Imamura K, Izumi Y, Nagai M, et al. Safety and tolerability of bosutinib in patients with amyotrophic lateral sclerosis (iDReAM study): a multicentre, open-label, dose-escalation phase 1 trial. EClinicalMedicine. 2022;53:101707. doi:10.1016/j.eclinm.2022.101707

By Heidi Moawad, MD
Heidi Moawad is a neurologist and expert in the field of brain health and neurological disorders. Dr. Moawad regularly writes and edits health and career content for medical books and publications.