Ask Dr. Mike: What Are the Latest Theories on ALS?

Additional Info

• Segment Number: 5
• Audio File: healthy_talk/1522ht4e.mp3
• Featured Speaker: Mike Smith, MD
• Organization: Life Extension
• Guest Website: Healthy Talk MD
• Transcription: RadioMD Presents: Healthy Talk | Original Air Date: May 28, 2015
  
  RadioMD. It's time to ask Dr. Mike. Do you have a question about your health? Dr. Mike can answer your questions just email AskDrMikesSmith@RadioMD.com or call now (877) 711-5211. The lines are open.
  
  DR. MIKE: So, a listener named Mary sent me an email and said,
  
  "I just watched the movie The Theory of Everything about Stephen Hawking. I was just curious about what causes ALS."
  
  All right. So, we're going to look...So, I'm going to use this as an opportunity to talk a little bit about Amyotrophic Lateral Sclerosis or Lou Gehrig's disease, ALS, and, again, focusing more on what we think are the current causes. It's a motor neuron disease. It's really affecting the nerve to muscle junction.
  
  It breaks it down. There's muscle wasting. It becomes hard to swallow. It can even affect the respiratory muscles and it's just this progressive disease. Once there's a diagnosis of ALS, the prognosis is quite poor, even still today, two to five years is the expected life expectancy. Once somebody, unfortunately, is diagnosed with ALS, the treatments have gotten a little bit better. We're able to extend life a little bit and there's some new stuff there but the focus here, for Mary, is on what are the causes of ALS.
  
  I saw the movie too, great movie, incredible acting. I forget who that actor is that played Stephen. I mean, incredible acting but they didn't really get into the disease itself it was definitely more about Dr. Hawking's life, his work and how ALS was affecting all that but it wasn't about ALS too much. So let's get into this, Mary.
  
  What are the latest theories? We don't know what exactly causes ALS. It's still a mystery. I think when I first learned about it--and this is back in the early 90's--when I was in medical school and at the University of Texas in Dallas, most of the theories were centering around a post-viral infection and there was even some thought that maybe there's even an autoimmune component here.
  
  So, you get this viral infection and your body over responds to the virus and there's what we call kind of like a cross reaction to normal receptors at that neuro muscular junction and your immune system starts to eat it up and but that hasn't really panned out all that much. I don't think there's been much headway in this post viral infection type theory. There are some other things, Mary, that have come up in the last, say, decade or so about the causes.
  
  The first one is a genetic mutation and it's a genetic mutation in a gene called SOD1, S-O-D 1, and this gene's normal codes for very important enzyme called superoxide dismutase. So, SOD1 is a gene that codes, or makes, or produces superoxide dismutase. That enzyme SOD-- it's one of the most powerful antioxidants we have and it helps to control the superoxide free radicals that can form in the body just from normal metabolism and some of those superoxide pro-oxidant compounds are very damaging if they build up.
  
  So, the theory is and, by the way, Mary, this theory about this mutation really began with a recognition that about 20% of all ALS cases have a family link. Out of those cases, the 20% that are familial, 2% have this SOD1 gene mutation. So, the theory is that maybe there's the SOD1 gene, which is very complex, that can have multiple mutations and what are called polymorphisms and that's leading to the inability to produce normal functioning superoxide dismutase which then leads to a buildup of oxidative stress.
  
  So, that's one theory. Interestingly they've been looking at this for a while now, Mary, this SOD1 gene mutation and through the research just kind of looking at the gene trying to figure out where the mutations are at and what mutations are worse, they've come up with some other theories from that--this gene mutation.
  
  This SOD1 gene mutation can damage neurons in other ways, outside of not being able to make superoxide dismutase, and so they have found that mutant SOD1 genes produce, again, these abnormal superoxide dismutase molecules which can lead these enzymes--the super oxide dismutase enzymes--to clump together. That clumping disrupts that neuromuscular junction that, even in the neurons in the brain, it disrupts how they communicate together, almost like an amyloid beta type picture in Alzheimer's disease. So, here you have a theory that says a mutation in the SOD1 gene produces an abnormal superoxide dismutase which then allows the buildup of very powerful free radicals based on a compound called superoxide pro-oxidants.
  
  So, you get this huge oxidative stress that damages the neurons, damages the neuromuscular drum and there's your problem but then they go onto say that this gene mutation produces such an abnormal SOD enzyme that they clump and that it almost causes an Alzheimer type picture not with amyloid but with clumping of superoxide dismutase. So, that's one theory, this SOD1 gene mutation. Another theory is just the oxidative stress theory. You know, studies have found elevated levels of oxidative stress in the central nervous system and just in the periphery in your normal blood stream in ALS patients. Of course, oxidative stress can damage neurons and, as a matter of fact, it's one of the theories of Alzheimer's disease.
  
  So, a lot of people do believe that although antioxidants aren't going to necessarily treat ALS, they are going to play an important role in controlling the progression. So, the beta carotenes, vitamin C, vitamin E, selenium, the pigment in antioxidants like zeaxanthin and lutein, because they can get into the brain, all can play a very, very important role in at least maybe controlling the progression of disease.
  
  Another theory is glutamate toxicity. Now, glutamate is a neurotransmitter and it's an important neurotransmitter. Under normal conditions glutamate is really, really tightly regulated because if you get too much glutamate, it over excites the brain and that over excitation can lead to seizure disorders, dementias and the theory is ALS and it appears that this system, this glutamate regulating system, is abnormal in patients with ALS. This results in the accumulation of glutamate and this excess glutamate level in the brain over excites the nerves beyond their capacity to function normally. It can eventually lead to nerve cell death.
  
  Dr. Shaw, in 1995, showed that patients with ALS do, in fact, have elevated levels of glutamate in their cerebral spinal fluid and that does support this hypothesis. By the way, too, one of the drugs used to treat ALS is kind of an anti-glutamate drug. It's called Riluzole and it is a drug that brings down the glutamate levels. It works so that supports some of that theory.
  
  Lastly, mitochondrial dysfunction, I don't have a lot of time to go into that but when you don't have normal functioning mitochondrial within the brain cell, which is a very active cell, the amount of cell energy production drops off significantly which is ATP. The brain cell then becomes dysfunctional. Once that happens free radicals build up inside the cell and you get kind of this high level of intracellular oxidative stress and that can lead to damage as well.
  
  This is Healthy Talk on RadioMD. I'm Dr. Mike. Stay well.
• Length (mins): 10
• Waiver Received: No
• Host: Mike Smith, MD