Amyotrophic Lateral Sclerosis (Lou Gehrig’s Disease)

Overview

Amyotrophic Lateral Sclerosis (ALS) (also known as Lou Gehrig’s disease) is a relentless and fatal neurodegenerative disease that damages and destroys nerve cells, known as motor neurons, in the brain and spinal cord. Motor neurons control the communications between the brain and voluntary muscle movement. When these communications break down in ALS patients, it becomes difficult and then impossible to control movement; eventually, the muscles waste away.

ALS can occur in people throughout their lifetimes, but predominantly manifests in people between the ages of 40 and 75. ALS is characterized by a progressive loss of voluntary motor activity (including speech, swallowing, and respiratory function), muscle weakness, and spasticity—all due to the degeneration of the motor neurons. First, ALS affects legs, arms, and the muscles involved in speech and swallowing; ultimately, the disease affects all voluntary muscles, resulting in paralysis. When the muscles responsible for controlling breathing fail, patients must rely on a ventilator for respiration. Generally, the intellect and cognitive abilities of ALS patients remain intact (Stephen Hawking is a well-known example.) The causes of ALS are largely unknown and the presentation of the disease is highly variable; however, all ALS patients suffer significant loss of motor neurons leading to muscle weakness, paralysis, respiratory failure, and ultimately death. [1] The disease has an extremely rapid onset, with an average survival time of 2 to 5 years after diagnosis, with significant variability between patients. [2]

Each year, approximately 5,600 people are diagnosed with ALS in the United States. [3] The lifetime risk of developing ALS is approximately 1 in 2,000; this corresponds to approximately 30,000 affected individuals in the United States. [4] 5% to 10% of ALS cases are familial—meaning a mutation is inherited in one of several genes known to cause the disease—but the majority of ALS cases are sporadic with unknown causes. [5]

For the thousands of patients living with ALS, there is no existing therapy that can cure or effectively treat their condition. There currently exists only one FDA-approved compound, Rilutek, which extends lifespan by a maximum of three months. [6] With no cure, ALS treatment focuses on supportive care, such as physical, speech, and occupational therapy, symptomatic treatment, mobility aids, and nursing support. [7]

The cost of caring for a late-stage ALS patient on a respirator can range anywhere from $200,000 to $300,000 per year. [8]

Progress towards a cure

With more than $56 million in funding from Proposition 71 and the California Institute for Regenerative Medicine (CIRM), researchers are working to develop ways to slow or halt the progression of ALS. [9] This funding has gone to an array of projects: many scientists are working towards understanding the disease and why the motor neurons die; others focus on how to treat the disease and its progression from a clinical standpoint.

One promising clinical project, headed by Dr. Clive Svendsen at Cedars-Sinai Medical Institute, is examining whether stem cell therapy can allow ALS patient to regain movement in their legs. Svendsen’s team has just filed an Investigational New Drug (IND) application with the Food and Drug Administration (FDA); the team will soon begin a human clinical trial to test the proposed therapeutic approach. The objective of the trial will be to see whether stem cells can help repair and regenerate damaged nerve cells, possibly allowing ALS patient to regain movement in the legs, and slowing the progression of ALS. [10]

In a “first-in-kind” clinical trial, the Cedars-Sinai team will use a combination strategy that uses neural progenitor cells—a type of stem cell—to target a specific treatment to the dying motor neurons in patients with ALS. [11] The team will modify these neural stem cells to produce a growth factor called glial-derived neurotrophic factor (GDNF), which is a protein that promotes neuronal health. These GDNF-modified stem cells will be transplanted into the patient, where they will function as “Trojan horses,” carrying the GDNF to afflicted areas, in order to stimulate and repair sick or dying motor neurons. This transplantation is precise enough for the scientists to target just one leg, and then compare the progression in the non-treated leg, to see if the modified cells slow the disease’s progression. [12]

Another research project at the University of California, San Diego, led by Drs. Larry Goldstein, Samuel Pfaff, and Martin Marsala, aims to protect surviving neurons in people diagnosed with ALS from further degeneration. [13] The team intends to take human embryonic stem cells, and then turn them into a type of stem cell known as astrocyte precursors. These develop into support cells known as astrocytes: support cells that envelope and provide vital nutrients to motor neurons. By transplanting astrocyte precursor cells into ALS patients, the scientists hope to slow the progression of motor neuron death, thereby slowing or halting the progression of ALS. [14]

Selected disease and research progress information provided by the California’s stem cell research funding agency, the California Institute for Regenerative Medicine (CIRM). Visit www.cirm.ca.gov for more updates.

Footnotes

[1] Goldstein, Lawrence et al.  “Stem Cell-Derived Astrocyte Precursor Transplants in Amyotrophic Lateral Sclerosis.” California Institute for Regenerative Medicine.  Web.  Accessed 25 February 2016.  https://www.cirm.ca.gov/our-progress/awards/stem-cell-derived-astrocyte-precursor-transplants-amyotrophic-lateral-sclerosis

[2] Ginsberg G, Lowe S. Cost effectiveness of treatments for amyotrophic lateral sclerosis: a review of

the literature. Pharmacoeconomics 2002;20(6):367-87.

[3] “Quick Facts About ALS & the ALS Association.” ALS Association.  Web.  Accessed 25 February 2016.  http://www.alsa.org/news/media/quick-facts.html?referrer=https://www.google.com/

[4] Goldstein, Lawrence et al.  “Stem Cell-Derived Astrocyte Precursor Transplants in Amyotrophic Lateral Sclerosis.” California Institute for Regenerative Medicine.  Web.  Accessed 25 February 2016.  https://www.cirm.ca.gov/our-progress/awards/stem-cell-derived-astrocyte-precursor-transplants-amyotrophic-lateral-sclerosis

[5] Id.

[6] Miller, RG et al.  “Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND).”  Cochrane Database Syst Rev. 2012 Mar 14;3:CD001447. Web.  Accessed 25 February 2016.  http://www.ncbi.nlm.nih.gov/pubmed/22419278

[7] Booth-Clibborn N, Best L, Stein K. Riluzole for motor neuron disease. 1997.

[8] Svendsen, Clive.  “Progenitor Cells Secreting GDNF for the Treatment of ALS.”  California Institute for Regenerative Medicine.  Web.  Accessed 25 February 2016.  https://www.cirm.ca.gov/our-progress/awards/progenitor-cells-secreting-gdnf-treatment-als

[9] “Amylotrophic Lateral Sclerosis (ALS) Fact Sheet.”  California Institute for Regenerative Medicine.  Web.  Accessed 9 March 2016.  https://www.cirm.ca.gov/our-progress/disease-information/amyotrophic-lateral-sclerosis-als-fact-sheet

[10] Id.

[11] Id.

[12] Id.

[13] Goldstein, Lawrence et al.  “Stem Cell-Derived Astrocyte Precursor Transplants in Amyotrophic Lateral Sclerosis.” California Institute for Regenerative Medicine.  Web.  Accessed 25 February 2016.  https://www.cirm.ca.gov/our-progress/awards/stem-cell-derived-astrocyte-precursor-transplants-amyotrophic-lateral-sclerosis

[14] Id.

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