POLL: Biomarkers
 

I've been interested in the role of biomarkers for some time now and Debi Brooks recently posted to the thread on the New Year--New Look at Research
that significant progress is being made on the MJFF research front in this very crucial area:

Also, our significant work in biomarker discovery (and soon to be announced next-step biomarker verification) might result in more predictive measures -- an essential need for clinical design improvements and a boost for clinical practice as well.

From what I've gathered on establishing biomarkers, it's important not only in getting a more scientifically sound, accurate diagnosis, it also becomes an important player in validity of clinical trial outcomes and eventually in treatment. For background on the MJFF research initiative and the role of biomarkers in general see the MJFF Research Paper.

Given this news, a few (more) questions on biomarkers come to light.

Since there is currently no way to halt disease progression, it seems that the use of biomarkers would solely be limited to aiding in diagnosis at this point? I wonder, then, how this would pan out in the doctor's office when they are given tools or guidelines to more accurately diagnose (may be able to target people much earlier on) in the absence of a cure or any better treatment standard than what is available right now? In light of this, would you want to know that you most definitely had PD years earlier than your original diagnosis? I think there are serious psychological ramifications here and wonder how all this will play out. Maybe biomarkers will not be used until we have a disease modifying treatment in place?

I'm also curious as to what "weight" the biomarkers will have in diagnosis without the aid of technology like SPECT scans or analysis of cerebrospinal fluids? We definitely need this component if we are to accurately use biomarkers in diagnosis. Some of the more observational or clinical biomarkers that are being studied are the presence of REM sleep disorder and anosmia or decline in ability to smell. What if people present without these markers (just wondering because I would not be a match here)?

No real answers, but just figured it was worth examining whether we would really want to know at age 25 that we were most likely going to develop a neurodegenerative disease in the future? Would that have made a difference for you?

Just for fun, I've added a poll to see how many of us conform to some of the biomarkers being researched.

Laura

I agree Laura that until a definitive treatment that consistently shows its ability to reduce progression is found, early diagnosis for the person involved would likely be no more than a source of anxiiety. The only benefit I suppose would be from a research point of view as they may qualify for studies involved in looking at neuronal protection.
One point mentioned in the MJFF Research Paper is: Disease rate biomarker: a marker of disease progression over time (particularly important for developing treatments that can slow or stop a disease). I agree with you: that could potentially help in research studies by evaluating early success of a specific intervention if it has been shown that ultimately the reduction in biomarker levels translates to improved clinical outcome.

suggestion
 

Another that might be added both because it seems widespread and because the PWP can easily identify it is an exagerated acoustic startle reflex - i.e. "jumping out of our skin" in response to unexpected noises.

biological markers
 

I understood that the major reason for finding or establishing biomarkers is the one mentioned by Soania, that they are needed to accurately assess disease progression and provide a biological marker (aha!) against which to determine if a treatment is actually slowing or stopping progression.

Learning of the earliest biomarkers in the disease, and how they appear in the progression of the disease, will help researchers more accurately target potential remedies. As things stand right now, treatment development and assessment of efficacy is largely a shot in the dark. Whether or not a drug is said to work is based on clinical observation, without parallel determination that the biological progression of the disease has actually been altered in any way.

Scratch and Sniff
 

Rick,

I agree with you that there will probably be some things that research overlooks- I'm going with the 'major' markers targeted by researchers. Right now in clinical trial, there is a biomarker study that targets only 3 in our poll (anosmia, REM Disorder, and Hypotension). I have read that gastric changes and anxiety/depression were also prevalent but I don't know they're being tested. I was surprised; however, to learn that hypotension was being marked.

As for use in diagnosis, I'm just going by what is posted at MJFF, but maybe I'm extrapolating where not warranted. According to the report:

Disease state biomarker: a 'diagnostic' marker that a given individual has PD (particularly useful for distinguishing PD from other PD-like diseases or for identifying individuals in the earliest stages of the disease).

Clinical measures (e.g., tests of motor ability, presence of disease-associated symptoms such as olfactory deficits, sleep disorders, constipation or early speech problems) can be good markers, but it may be necessary to combine more than one for reliable results. These measures are also not necessarily Parkinson's-specific.

Right now, there is actually a scratch 'n sniff card used in research now; the University of Penn Smell Identification Test. Even more interesting is that there is a small percentage of us (10% or so) who do not lose sense of smell and there may be a differential here between having Parkin Disease (hereditary) and Idiopathic PD. Not to say that this test is the be all and end all, but I fall into that minority range, and would really like to know more of genetics involved here for sake of my young son.

Laura - I think "diagnostic" in this case means being able to establish presence of the disease by using tools other than clinical observation, the only tool available to us right now, and one that is unreliable in predicting or proving the disease itself or its progression.

One advantage to knowing...
 

Hello, everyone. Long time, no post. But I do want to say that I think there is one big advantage to knowing if you had PD for many years before diagnosis, and so I would have definitely wanted to know. Knowledge is always better in my book. I'm convinced I had PD for many years before diagnosis, because I had many troubling symptoms which I now believe were likely due to PD. But I could never get any help or resolution or respect for my complaints, and was dismissed by med community (and sometimes by friends, family, coworkers, etc.) as an unstable malingerer or hypochondriac, or prescribed things that didn't help or made things worse. Wasted a lot of time, money, and bad energy trying to figure it out, even sometimes blaming/questioning myself. Wouldn't it be better to at least know there's a legitimate cause of your miseries?

Yes, I had 2 of the poll symptoms (depression/serious anxiety, digestive problems), but also others that have been suggested as PD-related, mainly serious joint/muscle pain & stiffness (esp. on R side shoulders, back, jaw, neck, ribs, etc.), sleep problems (greatly improved by a sleep apnea mask a few years back; check it out!), a scalp condition, smelly armpits (esp. on R side; sorry, but true), fatigue, extreme startle response, nervousness, plus others I can't think of right now (memory issues!).

About 10-15 years before my diagnosis, when I was prescribed nortriptyline (Pamelor, I think) for 1 year for depression, it seemed to suddenly bring out some of the PD symptoms that I now have (slight stammering, forgetting words/names, memory problems, cognitive problems, plus others) and did nothing to improve my mood. The PD symptoms mostly disappeared (but perhaps not entirely) when I went off it after a year. Sometimes I worry that some depression meds, and possibly some PD meds, can actually worsen progression of PD, though they may seem to improve some symptoms for some people some of the time. (We're all so different.)

My main symptom now is a huge tremor, but 3 years in from diagnosis, I'm still not on meds yet because I distrust them & worry about both short & long term side effects. Still relying on supplements (creatine, CoQ10, resveratrol, vitamins, etc.), amlodipine (couldn't get isradipine), and estrogen patch, plus exercise, and as much positive spirit as I can muster (varies!!). I may have to accept the meds soon, but I'm pushing it as far as I can, because based on my observations of my real-life PD groups here, the side effects (cognitive, sleepiness, low energy, dyskinesia) may sometimes be worse than the condition, unless of course you really need them in order to function.

biomarker
 

Laura,
Good topic. Biomarkers are badly needed for PD and your list is great! I can think of a couple more to add to your list. Frozen shoulder/rotator cuff tear/or similar shoulder problems seem to quite common among PWPs. We had a discussion on this subject a while back......

Having said that, we need a more definitive set of biomarkers that are unique to PD. These markers ideally are linked to specific biological changes that induce or promote PD. I think alpha-synuclein is one such candidate in my opinion. I have not looked carefully in the literature as to if this protein or something related to it can be detected in the blood or other biological samples in PWPs compared to non-PD samples. Since it seems so obvious, I am inclined to think someone would have done it already! Did you or anyone else come across any reports related to alpha-syn as a biomarker?
Just something to think about.......if its not out there....

girija

I assume that it would be part of a cluster forming a marker, but one possibility might be inflammatory cytokines such as TNF-a.