Crystal Ball for Parkinsons?

One-million Americans are living with Parkinson’s disease. Right now – there’s no way to tell these patients if they will have a mild or severe form of the disease. Now –a simple blood test may give Parkinson’s patients a glimpse into their future.
Michael Weinman has been living with Parkinson’s for 14 years. The degenerative disease has slowly robbed him of the ability to perform everyday tasks.
“I used to be able to run,[but] I can’t run anymore,” Weinman told Ivanhoe. “I used to be able to carry my food to the table, I can’t do that [anymore].”
However, Michael has kept a positive attitude through it all.
“I try to focus on what I can do,” Weinman said.
“Definitely, he’s a glass half-full,” Weinman’s wife, Nessa, told Ivanhoe.
While Michael’s disease has progressed slowly, Parkinson’s patients don’t know whether their disease will be mild or severe when they are diagnosed.
“Nobody who is a neurologist and sees patients can very well predict who will rapidly decline eventually need a wheelchair quite fast,” Beate Ritz, MD, PhD, Chair, Dept. of Epidemiology Center for Occupational and Environmental Health, Fielding School of Public Health, UCLA, told Ivanhoe.
Dr. Beate Ritz and colleagues studied recently-diagnosed Parkinson’s patients. They took blood samples and found those with higher levels of a metabolite called N8-acetyl spermidine, declined much faster than those with lower levels.
“We found that this one metabolite seemed to really distinguish these two groups from each other,” Dr. Ritz explained.
Weinman and his wife hope research like this will help others. They also walk in the annual “Mike Hike”, which has raised over $40,000 for Parkinson’s.
“Hopefully in the future, they’ll be able to treat it and recognize it sooner,” Weinman said.
Doctors say the next step is to conduct a larger study on this metabolite as a predictor of faster progression.


BACKGROUND:   Parkinson’s disease is a condition of the brain affecting approximately six million people.  It is most commonly characterized by slowness of movement, stiffness, shaking, and loss of balance.  Parkinson’s often develops after the age of 50.  Although Parkinson’s disease is one of the most common nervous system disorders for the elderly, it can affect young people too, usually because a form of the disease runs in their family.   Nerve cells use a brain chemical called dopamine to control muscles.  When the nerve cells in the brain that produce dopamine are destroyed as a result of Parkinson’s, the nerve cells in that particular part of the brain will not properly send messages.  The result is the loss of muscle control.  The damage gets worse over time. (Source:
TREATMENT:  A doctor may be able to diagnose the disease based on symptoms alone, but symptoms can be difficult to access in the elderly.  Unfortunately, there is no known cure only a treatment plan to control symptoms.  Medicines for Parkinson’s are designed to control symptoms usually by increasing levels of dopamine in the brain.  Throughout the day the medications can wear off and symptoms can return.  Parkinson’s requires the patient and doctor to work closely with each other to find the right treatment plan that works best.  Common medications are Levodopa (L-dopa), Pramipexole (Mirapex), Selegiline (Eldepryl, Deprenyl), Amantadine or anticholinergic medications to reduce early or mild tremors, or Entacapone to help control movement.  Other medications include:  Memantine for cognitive difficulties, Antidepressants, Gabapentin for pain, Fludrocortisone for autonomic dysfunction, and Armodafinil for sleep disorders. (Source:
NEW TECHNOLOGY: Researchers at the UCLA Fielding School of Public Health have identified a metabolite that seems to be a marker for a more severe form of the disease. After studying nearly 6,000 metabolites in the blood of people with Parkinson’s, they found one, called N8-acetyl spermidine, was associated with a quicker worsening of Parkinson’s symptoms. Patients were followed for 10 years, and those who had a more severe disease had higher levels of the metabolite. Researchers now have to find out if catching the disease early enough can help patients. (Source: Dr. Beate Ritz)

Mark Wheeler
Senior Media Relations Rep
UCLA Health Sciences Media Relations

Beate Ritz, MD PhD, Chair Dept. of Epidemiology, Center for Occupational and Environmental Health, Fielding School of Public Health, UCLA, talks about a new way to detect Parkinson’s disease.

Can you tell me what you do in your Parkinson’s studies?   
Dr. Ritz: Actually what I do is conduct studies of Parkinson’s disease in people living in their communities who we follow and watch over 10 years. We selected patients living in the Central Valley of California. Our movement disorder specialists saw them several times and assessed all of their functions including their motor and cognitive function. Patients also provided us with blood samples early in disease.  We were able to use these blood samples to find a marker that predicts who was going to be doing worse in terms of motor function over time.  
 Is it almost like a finger print, sort of?
Dr. Ritz: Yes, almost. It’s a marker. It’s one molecule and it’s called N8-acetyl spermidine. A complicated name, but it is a metabolite of polyamines that kind of floats around in your blood, in your serum. The patients, in the beginning of our study, have about the same function, motor function, and general physical capabilities, but they can be distinguished in terms of this metabolite. 
Did they have mild Parkinson’s?
Dr. Ritz: Yes, relatively mild Parkinson’s. They were just diagnosed between 1 and 3 years into their disease.
Did they have any symptoms yet?
Dr. Ritz: Oh yes, otherwise we couldn’t have diagnosed them. They had the typical Parkinson’s motor symptoms and were diagnosable with Parkinson’s disease due to their symptoms, but they were doing fairly well. They were able to participate in the study and allowed us to see them multiple times.  It turns out that early in disease when everybody looks about the same, no neurologist can actually predict who among these patients will rapidly decline in function, not being able to move very well, or who amongst them will actually do fairly well, having maybe a little shake and stiffness but be otherwise quite functional. We watched these patients over time, monitored and recorded their symptoms, and then searched for  something that might predict their  progression. That’s when we realized that we may want to use the blood samples collected at the beginning of the study. We decided to try and figure out whether there is a molecule in their blood that may actually allow us to predict who belongs to which group in terms of progression of symptoms.
How did you find this molecule and does it change over time? 
Dr. Ritz: It’s a metabolite, which is a small molecule in your blood that comes, for example, from your metabolism. Our cells’ metabolism produces these kinds of small molecules, , called metabolites.  We had about 6,000 metabolites that we were able to identify with our method. Out of those, we found this one metabolite of polyamines, molecules that can modulate cell growth and proliferation and interact with our genes, which seems to really distinguish these two groups of patients from each other.

Would you have a higher level of metabolites if you were going to decline rapidly?
Dr. Ritz: Yes, you’d have a higher level of that certain metabolite in your blood. 
Is there a number that cuts it off?  
Dr. Ritz: We can’t really say how much is too much yet. Since one study never gives you all the answers, we need replication of this finding. What really intrigued us was that it was a substance that has been shown to increase with neuronal cell death, and in Parkinson’s disease dopamine neurons are dying. It has been shown to be excreted more by people who have neuroinflammation, or injuries to neurons, so it might be one of the metabolites that you could actually see at an increased rate in your blood when certain neurons die. 
Is there anything you can do to lower the increased rate? 
Dr. Ritz: That would be the next step. First of all, we need replication. We need to see whether this was a chance finding, which can always be the case, or whether somebody else has kept blood of patients and data on their patients’ progression over time. Our study started in 2001 and we have follow-up data for these patients for a long time.  We need another study in which somebody actually looked at the progression of patients over time and will try to identify this metabolite and see whether this agent can also split their progressors into two groups: fast and slow.
Do you think that people without any symptoms of Parkinson’s would show that you have the disease?
Dr. Ritz: No, because we actually had also enrolled people who did not have Parkinson’s disease. We were really interested in finding out whether we would be able to distinguish Parkinson’s patients from non-patients. Interestingly, in that early stage of disease, the controls and the slow progressors looked rather similar.  However, we could identify the ones who took off and really didn’t do very well over time. The good thing is, that if our results can be replicated  we may be able to not only predict which patients with Parkinson’s get worse over time, but also can more effectively try to  prevent these people from getting worse. When we diagnose them, they are fairly functional. What everybody is really worried about is the future decline in function, which might be very fast and which we would want to stop. 
If you catch Parkinson’s early, is there anything that will help stop the progression?  
Dr. Ritz: That’s what we hope. This is the first step into that direction, we think, to find out why these patients have this metabolite in their blood. Then, if this is not a metabolite we can lower or we can use to save the cells that are working very hard in these patients’ brains; at least we could use this marker to split patients into two groups for clinical trial. In patients who are faster progressing in a short time, you would see whether the drug you are proposing to use to prevent progression actually works.  In people who over 10 years slowly decline, you will need to watch them for as much as 10 years when you enroll them  in drug trials. If this metabolite is really a good marker of fast progression, you could select out this group and be able to see within 2 or 3 years or maybe six months whether your drug is effective in preventing progression. Whatever agent you have and want to use for preventive trials, this might be a very good marker to find these people.
Would this be able to show the same thing for Alzheimer’s? 
Dr. Ritz: Alzheimer’s and Parkinson’s are different diseases.  They are similar in a sense that there seem to be certain proteins you can pick up in the spinal fluids of patients, more so for Alzheimer’s than for Parkinson’s.  For Parkinson’s we really haven’t found this reliably yet.  They’re two different diseases, two different cell types that are dying, and  different proteins that are involved.  However, there is some overlap. Some Alzheimer’s patients also become Parkinsonian and a lot of Parkinson’s patients have cognitive impairment after a while. That is  there is some overlap in the symptomatology –especially in advanced disease stages-, but they’re really two different diseases.  Whether this would work for Alzheimer’s, we don’t know.
I mean, it seems so simple, blood test.  
Dr. Ritz: Yes, that’s also why a lot of neurologists don’t really believe it. They believe that you really need to test the spinal fluid because that’s what the brain cells that die communicate with and that the blood is too far removed from the organ that’s failing. Of course, it is much easier to get a blood test than to get spinal fluid from someone, right? So really, what we want is to develop a blood test eventually.
Now, to test the blood and find the spinal marker, we’re hearing this a lot lately with this mass spectrometry, can you tell me a little bit about that?  
Dr. Ritz: Yes, that’s what we used. We used mass spectrometry. 
What does that do? 
Dr. Ritz: Mass spectrometry is just a tool that chemists are using to identify these kinds of small molecules.  They run the fluid (such as our serum from blood) through this machine that picks up signals and because every molecule is made out of different atoms, there is a different spectrum of signals that you can identify. It’s like a name tag for a molecule.  The machine picks out molecules and we are able to name tag them and we can find out what they are.   
Perfect. Now, so what’s next for this?  
Dr. Ritz: We hope that we can repeat this with a new set of patients, but we would also hope that somebody picks this idea up and in the lab goes after the pathway and identifies how this metabolite may actually be involved in neurodegeneration.  If this molecule really can identify the faster progressing Parkinson’s patients, we hope that this will help inspire trials that will eventually prevent progression.
I think the hard part is that it’s not a quick fix right now because to do anything you have to watch the progression of Parkinson’s patients.  
Dr. Ritz: Right.  It’s not a quick fix, but it is the first step in the right direction. 

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