What is Amyotrophic lateral sclerosis?
Amyotrophic lateral sclerosis (ALS) is a rare neurological disease that primarily affects the nerve cells (neurons) responsible for controlling voluntary muscle movement (those muscles we choose to move). Voluntary muscles produce movements like chewing, walking and talking. The disease is progressive, meaning the symptoms get worse over time. Currently, there is no cure for ALS and no effective treatment to halt or reverse the progression of the disease.
ALS belongs to a wider group of disorders known as motor neuron diseases, which are caused by gradual deterioration (degeneration) and death of motor neurons. Motor neurons are nerve cells that extend from the brain to the spinal cord and to muscles throughout the body. As motor neurons degenerate, they stop sending messages to the muscles and the muscles gradually weaken, start to twitch and waste away (atrophy). Eventually, the brain loses its ability to initiate and control voluntary movements.
What are the Common Signs and Symptoms?
Early symptoms of ALS usually include muscle weakness or stiffness. Gradually all voluntary muscles are affected and individuals lose their strength and the ability to speak, eat, move and even breathe. Most people with ALS die from respiratory failure, usually within 3 to 5 years from when the symptoms first appear. However, about 10% of people with ALS survive for 10 or more years.
ALS was once commonly known as Lou Gehrig’s disease, following the retirement of the famous ballplayer in the 1940s due to the disease. Another famous person that had ALS was the theoretical physicist Stephen Hawking.
The symptoms and signs vary greatly from person to person, depending on which neurons are affected. It generally begins with muscle weakness that spreads and gets worse over time. They can include:
- Difficulty walking or doing normal daily activities.
- Tripping and falling.
- Weakness in legs, feet or ankles.
- Hand weakness or clumsiness.
- Slurred speech or trouble swallowing.
- Muscle cramps and twitching in the arms, shoulders and tongue.
- Cognitive and behavioral changes.
What Causes ALS?
The disease affects the nerve cells that control voluntary muscle movements such as walking and talking, known as motor neurons. ALS causes the motor neurons to gradually deteriorate and eventually die. Motor neurons extend from the brain to the spinal cord to muscles throughout the body and when they are damaged, they stop sending messages to the muscles and they stop functioning.
ALS is inherited in 5-10% of people, for the rest the cause is not known. Researchers continue studying the possible causes of ALS. Most theories center on a complex interaction between genetic and environmental factors.
Some established risk factors include:
- Heredity. 5-10% of cases are inherited (familial ALS). The children have a 50-50 chance of developing the disease.
- Genetics. Some studies found many similarities in the genetic variations of people with familial ALS that make people more susceptible to ALS.
- Sex and age. ALS is more common in women before 65, but after 70 the sex difference disapears. The risk increases as we age and it is most common between 40-60 years of age.
- Smoking. Is the only likely environmental risk factor for ALS and the risk seems to be greatest for women, particularly after menopause.
Current Treatment Options
The only current FDA approved treatments are riluzole, an oral medication believed to reduce damage to motor neurons by decreasing levels of glutamate, and edaravone which is given by an intravenous infusion and has been shown to slow the decline in clinical trials. Nevertheless, none of the treatments have been able to decrease the mortality in this condition. One treatment that has been recently evaluated is the use of cellular therapies with stem cells.
Mesenchymal Stem Cells and Clinical Trials
MSCs readily differentiate into mesenchymal lineages, and in vitro manipulation can lead to differentiation into ectodermal lineages, including cells with neuronal or glial properties. Additionally, they secrete a broad variety of proteins including neurotrophic factors and immunomodulatory cytokines that could be beneficial in neurodegeneration. Different studies have shown benefit from the use of MSCs. Some of them are discussed below.
A small study from Korea treated seven patients with bone marrow-derived MSCs intrathecally with two doses separated by 26 days, with a 12 month follow-up. The rate of decline in both the ALS functional rating scale-revised (ALSFRS-R) and forced vital capacity (FVC) were reduced for the first 6 months after treatment compared to the lead in period, with the limitation that the study was small.
Another group from the Czech Republic recently reported on an open label phase 1//2a study delivering autologous bone marrow-derived MSCs intrathecally to 26 ALS subjects. Comparing posttreatment decline in ALSFRS-R to the lead in period demonstrated a transient decrease in slope of decline and had the same limitation of a small group and not being compared with a placebo group.
A group of researchers from Poland performed a study using Warthon’s jelly umbilical cord derived mesenchymal stem cells. The study involved 67 patients with ALS and received 3 intrathecal injections of MSCs every 2 months. They found that the median survival time increased two-fold in all groups of patients and that these type of MSCs are safe and effective in some ALS patients, regardless of the clinical features and demographic factors, excluding sex. The saw that the female sex and a good therapeutic response to the first administration of cells are significant predictors of efficacy following further administrations.
This group from Poland concluded that despite the limitations of their study, they suggest that the treatment with umbilical cord MSCs substantially reduces the rate of progression and yields an extension of survival in patients with ALS and that future studies should focus on confirming these observations in randomized controlled trials.
Stem Cell Therapy at Zignagenix
At our clinic we based our therapies and protocols following the recommendations of different research studies and utilize Umbilical cord-derived Mesenchymal stem cells (UC-MSCs) from the Warthon’s jelly tissue.
The therapy for ALS at the clinic consists in the application of UC-MSCs infused intravenously (IV) at high doses that are combined with exosomes. Also we use one of the best ways to deliver stem cells to the brain and the spinal cord through an intrathecal application that is performed by a physician with years of experience in these types of procedures. This way, they can travel directly from the cerebrospinal fluid to the brain and the affected areas.
Barczewska M, et al. Umbilical Cord Mesenchymal Stem Cells in Amyotrophic Lateral Sclerosis: an Original Study. Stem Cell Rev Rep. 2020 Oct;16(5):922-932. doi: 10.1007/s12015-020-10016-7. PMID: 32725316; PMCID: PMC7456414.
Baloh RH, Glass JD, Svendsen CN. Stem cell transplantation for amyotrophic lateral sclerosis. Curr Opin Neurol. 2018 Oct;31(5):655-661.
doi: 10.1097/WCO.0000000000000598. PMID: 30080719.