This is a continuation of the article run on last Wednesday about MSA Awareness month in Ohio. It is part of a dedication to Frank Cervone and his desire to make the world aware of MSA before it takes him:
Bob Summers, who you might remember lost his wife Sue to MSA last May received an update from Dr. Ide on his research on MSA. I would like to share it with you.
You asked me to post a description of the MSA research my lab is currently doing here at Western Michigan University. Here it is.
MSA is a neurological disease that involves three syndromes: Parkinsonism, Autonomic Failure, and Cerebellar Ataxia. To date, work carried out in my laboratory at Western Michigan University in collaboration with the New York Brain Bank at Columbia University and Vanderbilt University Medical School is defining changes in the activities of thousands of genes in MSA versus control patients. These studies are forerunners of “personalized medicine” where gene activities in, for example, blood cells, will be used to diagnose different disease types (e.g., MSA versus Parkinson’s versus Pure Autonomic Failure) as well as determining the most effective treatment for individual patients.
So far, our approach has revealed, in post-mortem brain tissues, and from blood samples from living patients, specific biochemical pathways that are compromised in MSA. Pathways that normally provide energy for cells and orchestrate the handling and recycling of misfolded/worn-out proteins are damaged, while, at the same time, pathways that control inflammation are hyperactive.
We follow up gene expression studies by determining which cell types in the MSA brain have changes in function, or are playing a role that might be detrimental to cell survival. We see in control tissues, healthy neurons in the cerebellum making a properly folded protein (alpha-synuclein) that helps the cells excite other cells that account for proper cerebellar function. In MSA tissues, these cells have dumped the protein, now misfolded and unable to function, out of the cells where it is taken up by cells that make myelin, a protein that is necessary for proper neuronal signaling.
We also see immune cells in the MSA brain, apparently destroying myelin, similar to what happens in Multiple Sclerosis, but in this case, probably due to the presence of the misfolded synuclein. We have also found several biochemicals in MSA brain cells that initiate inappropriate cell death.
Thus, our goal is to keep linking changes in gene expression with specific changes in cell chemistry and function in MSA brain cells to not only understand the underlying causes of the disease, but also, to find ways to restore function. For example, we need to understand why neurons in MSA do not degrade and recycle misfolded alpha-synuclein, rather than dumping it out of the cell where it causes major problems.
We need to determine the types of drugs (some already available?) that influence cells to turn on specific pathways for protein recycling. Will removal of misfolded proteins stop MSA progression, opening the door for an approach to neural regeneration? We have already seen some evidence in gene expression studies that the MSA brain is trying to repair itself. We hope to find a way to facilitate this process.
One project with Vanderbilt U. involves developing a clinical test to differentiate MSA from Parkinson’s (with some autonomic failure, termed Parkinson’s plus), and another from another condition termed Pure Autonomic Failure. Miracles for MSA funded the pilot work, i.e., blood samples provided by Dr. David Robertson at Vanderbilt Medical School. We found a unique group of genes for each disease whose expression characteristics may serve as highly specific biomarkers for diagnosing each condition. We need to follow up on this encouraging study.
Finally, my lab is about to start experiments using two drugs that are being used in Alzheimer’s trials. One drug is approved, but has some side effects; the second drug has no side effects, but is not approved yet, for general use. A local company, a start up by former Upjohn/Pharmacia scientists, is responsible for developing the drugs.
The drugs are supposed to enhance metabolic function through increasing transport of glucose related compounds into mitochondria, as well as turn on pathways that degrade misfolded proteins.
We showed in our global gene expression paper that MSA patients fail to make mitochondrial proteins at levels seen in controls; in other diseases, this has been attributed to decreases in metabolic drive/mitochondrial function, and has been related to neurodegeneration. Therefore, the drugs may obviate metabolic problems involved in MSA neurodegeneration. Additionally, the drugs are supposed to turn on autophagy, one of the pathways in the cell that degrades misfolded proteins, including, we hope, misfolded alpha synuclein in oligodendrocytes in MSA.
Our experiments utilize an oligodendrocyte culture system where we treat cells with synuclein and then measure the induction of three proteins we have shown are involved in cell death in MSA cerebellum and in MSA blood cells. We are hoping that the drugs will turn off these genes/proteins and rescue the oligodendrocytes from apoptotic cell death. This might encourage clinicians to try the approved drug on MSA patients.
As you can see, Dr. Ide is still extremely busy looking at things with very big words!! I don’t understand the terms, but I can explain what my journey is like in a way so that you can all relate to it.
Let’s say you have two bare electrical wires in your house and they short out. What happens? You trip a breaker in your fuse box, right? The myelin Dr. Ide refers to is like the colored coating on electrical wires. In my brain, the myelin or “coating” on the nerves is deteriorating and I short-circuit or “trip” a breaker and lose consciousness. Unfortunately, there isn’t a switch that anyone can flip to turn me back on. So when I went comatose that Sunday, I was “off” for more than 6 or so hours. It was totally up to God to determine when and if I would restore power. That is just one of the horrible things we live with everyday. It happens. I never have any recollection of it. As far as I can tell, when I come too, nothing happened. It’s my family and friends that sit by my side waiting to see if I will return to them that are affected emotionally by this.
This is just one reason I continue to fight so hard for funding for research. So families like mine don’t have to endure days like this. If you’d like to help, I have given a link below where you can make a tax-deductible donation to my organization, Hope For MSA. Every dollar that is raised is donated to Dr. Ide to assist him in continuing his research. MSA is a very under-diagnosed disease.
If you have been diagnosed with Parkinson’s, but medications aren’t quite effective, you could have MSA.
If you have been diagnosed with Orthostatic Hypotension or chronic low blood pressure, and there are other parts of your body that aren’t reacting normally, you may have MSA.
If you find yourself losing your balance often, walking is becoming more like shuffling your feet, and you know something is not right but the doctor can’t find it, it might be MSA.
Let’s all come together and help Dr. Ide to find a cause, find a cure for this. Please donate today. I know times are tough. Even if you can only donate a dollar, Dr, Ide will not only appreciate it; he will find a use for it. Let’s stop MSA!!
If you aren’t comfortable using your credit card online, you may send your check or money order to:
Greene Community Foundation
Hope For MSA
25 Greene Street
Xenia, Ohio 45385
Thanks again and share this story with your friends. After all, March is MSA Awareness Month. Oh, and try to wear something purple. It is our favorite color!!
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