Fryday, 28 August 2020 | Nina Klein

Does Stem Cell Therapy for Amyotrophic Lateral Sclerosis Work?

Amyotrophic lateral sclerosis (ALS) is a very serious disease of the central and peripheral nervous system. With the exception of the rare hereditary forms, its cause is still unknown. Even though they are often compared, ALS has nothing to do with MS (Multiple Sclerosis) - they are two completely different diseases.

About one to two out of 100,000 people develop ALS each year. The disease usually begins between the ages of 50 and 70; younger adults are rarely affected. Men are affected slightly more often than women (1.6:1). The frequency of ALS appears to be increasing worldwide. Disease progress varies greatly from patient to patient, and life expectancy is significantly shortened.

Currently, there is no known cure for ALS, but stem cell-based therapies may give patients, their doctors and scientists hope in dealing with this condition.

What is Amyotrophic Lateral Sclerosis - ALS?

 

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an expected survival of 2-5 years after the clinical onset. In Europe alone, 7-6 individuals out of 100.000 suffer from this condition, making it the most common motor neuron disease in adults above the age of 50 years. It is also more common in females than in males.

ALS affects almost exclusively the motor nervous system. This means that the system which controls our muscles and movements is impaired in patients with ALS. The sensation of touch, pain and temperature, seeing, hearing, smelling and tasting, the functions of the bladder and intestine remain normal in most cases. Minor mental impairments can occur in some of the patients, but serious impairments are rare.

What are the Symptoms of ALS?

Once motor nerve cells in the spinal cord and their extensions to the muscles are affected, the disease leads to involuntary muscle twitches (fasciculations), muscle wasting (atrophy) and muscle weakness (paresis) on the arms and legs and also in the respiratory muscles.

If the motor nerve cells in the brainstem are affected, muscles which control speech, chewing and swallowing are weakened. This form of ALS is also called progressive bulbar paralysis.

The disease of the motor nerve cells in the cortex and their connections to the spinal cord leads to both muscle paralysis and an increase in muscle tone (spastic paralysis) with an increase in reflexes.

What Causes ALS?

Loss of motor neurons in the brain cortex, brain-stem and spinal cord is the pathological mechanism (the mechanism by which a condition occurs) in ALS. However, the mechanism that causes neuron loss is not entirely clear.

It is believed that oxidative stress, defined as the production of free radicals (reactive oxygen species, short ROS), accumulation of certain proteins (SOD1, TDP43, ubiquitin and neurofilaments), and neuro-inflammation are responsible for the loss of neurons and subsequent progressive neurological symptoms like muscle paralysis, muscle wasting, muscle weakness, loss of body weight, fasciculation, emotional lability and cognitive dysfunction in ALS patients.

How is ALS Diagnosed?

The neurologist is responsible for the diagnosis. The patient is first examined clinically, in particular the muscles must be assessed with regard to muscle loss and strength as well as fasciculations. An assessment of language, swallowing act and respiratory function is also important. The reflexes must be checked. In addition, other functions of the nervous system that are usually not affected by ALS must be examined in order to identify similar but causally different diseases and to avoid misdiagnoses.

An important additional examination is electromyography (EMG), which can prove the involvement of the peripheral nervous system. Detailed investigations of the nerve conduction speed provide further information. In addition, examinations of the blood, urine and, for the first diagnosis, also of the liquor are required. Various imaging examinations are also part of the diagnosis.

How can Stem Cells Help ALS Patients?

Recent research has focused on the disease modifying effects of mesenchymal stem cell (MSC) Secretome. Although it is still unclear which ingredients of the MSC-Secretome are responsible for its effectiveness in ALS, several bioactive compounds have been identified, such as BNDF, GDNF, NGF, IGF-1 and VEGF, amongst others. These compounds have the potential to

  • exert a neuro-protective effect,
  • reduce apoptosis (= programmed cell death),
  • increase the secretion of neurotrophic factors by glial cells (the cells in the brain which support neurons),
  • reduce oxidative stress, and
  • modulate the inflammatory process in the brain (stimulation of M2 cells that liberates anti-inflammatory bio compounds).

Further effects of MSC-secretome which have recently been revealed are the removal of protein aggregates, by micro-glia activation (the macrophages of the brain which scavenge for cell waste products, cell debris and infectious agents) amongst other mechanisms.

The available scientific knowledge with regards to the efficacy of MSC-secretome in animal models that are suffering from ALS encourages the development of cell-free products that can potentially eliminate the need for cell transplantation strategies in the future.

Current research indicates that MSC-secretome is effective and safe in ALS patients, albeit still experimental treatment for ALS disease. Despite the lack of larger clinical trials, the available scientific data supports the use of MSC-secretome as promising new treatment for ALS disease that improve the clinical status of patients, slows the disease progression, and improve the quality of life.

Text

Study Name

Effect of Intrathecal Administration of Hematopoietic Stem Cells in Patients With Amyotrophic Lateral Sclerosis (ALS)


Intervention and Application

Intrathecal administration of stem cells


Status

completed


ID and Link

NCT01933321


Study Name

The Clinical Trial on the Use of Umbilical Cord Mesenchymal Stem Cells in Amyotrophic Lateral Sclerosis


Intervention and Application

Stem cell transplantation through lumbar puncture


Status

unknown


ID and Link

NCT01494480


Study Name

Dose Escalation and Safety Study of Human Spinal Cord Derived Neural Stem Cell Transplantation for the Treatment of Amyotrophic Lateral Sclerosis


Intervention and Application

Human spinal cord stem cell implantation


Status

unknown


ID and Link

NCT01730716


Study Name

Human Neural Stem Cell Transplantation in Amyotrophic Lateral Sclerosis (ALS) (hNSCALS)


Intervention and Application

Surgical microinjection of human neural stem cells on spinal cord of ALS patients


Status

completed


ID and Link

NCT01640067


Study Name

Autologous Bone Marrow Mesenchymal Stem Cells in the Treatment of Patients With Amyotrophic Lateral Sclerosis (UwmBmmscALS)


Intervention and Application

Autologous Bone Marrow Mesenchymal Stem Cells in the Treatment of Patients With Amyotrophic Lateral Sclerosis (UwmBmmscALS)


Status

unknown


ID and Link

NCT02881489


Study Name

Clinical Trial on The Use of Autologous Bone Marrow Stem Cells in Amyotrophic Lateral Sclerosis (Extension CMN/ELA)


Intervention and Application

human spinal cord stem cell implantation in ALS patients


Status

completed


ID and Link

NCT01254539


Study Name

Human Spinal Cord Derived Neural Stem Cell Transplantation for the Treatment of Amyotrophic Lateral Sclerosis (ALS)


Intervention and Application

Intrathecal injections into new subjects will be timed so that there is a minimum of one week between subject injections.


Status

unknown


ID and Link

NCT01348451


Study Name

A Dose-escalation Safety Trial for Intrathecal Autologous Mesenchymal Stem Cell Therapy in Amyotrophic Lateral Sclerosis


Intervention and Application

Autologous Mesenchymal Stem Cell injections


Status

active


ID and Link

NCT01609283


Study Name

Escalated Application of Mesenchymal Stem Cells in Amyotrophic Lateral Sclerosis Patients


Intervention and Application

2 intrathecal autologous MSCs infusions (1x10^8 cells)


Status

completed


ID and Link

NCT02987413


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