What comes first: the biomarker or the symptom, the aetiology or the cure?

Perhaps it's the result of my Parkinson's mentality, but I feel uncomfortable when I don't precisely understand words.

Take for instance, the word "biomarker".

The National Cancer Institute defines:
"[biomarker:] A biological molecule found in blood, other body fluids, or tissues that is a sign of a normal or abnormal process, or of a condition or disease. A biomarker may be used to see how well the body responds to a treatment for a disease or condition."
http://www.cancer.gov/dictionary?cdrid=45618

Wikipedia defines:
"A biomarker is a parameter that can be used to measure the progress of disease or the effects of treatment. The parameter can be chemical, physical or biological."
http://en.wikipedia.org/wiki/Biomark...ug_Development

The definitions may be similar, but I'd understand the first to exclude what we would normally call symptoms, such as rate of blinking (part of the Parkinsonian masked face), whereas the second one would include them.

Perhaps it's the Parkinson's again, but I'm always skeptical about fashions and, certainly, biomarkers are fashionable.

Both of the definitions suggest that biomarkers can be used to measure the effectiveness of a treatment. But, with something like Parkinson's, where the aetiology or aetiologies are unknown, the measure of success is mostly judged in terms of symptoms, e.g. before I couldn't walk, now I can. Given this, there is always going to be a need to use symptom based metrics. The real issue, it seems to me, is how to make these as valid, accurate, objective and convenient as possible.

It's that Parkinson's again, but I also have trouble with the term "Parkinson's Disease" itself. Is it defined by the symptoms or is it defined by the causes of these symptoms? By the tremor and slowness, etc., or by a shortage of dopamine, etc.? Once we start talking about causes, we naturally get on to asking what causes the causes, and so on. There could be several different levels of causality for each of many different types of Parkinson's.

The relevant biomarkers will depend on the aetiologies. For instance, if h. pylori played a part in the aetiology of PD that could be measured. But wait: we need the biomarkers to find the aetiologies of the disease. A circularity.

Clearly, knowing the aetiologies of PD would help in finding cures. Equally, knowing the cures would help find the aetiologies. It will be interesting to see what comes first.

John

It is always easier if you use a simple example. Let's say low blood pressure. The symptoms are feeling dizzy if you get of your chair. The biomarker is measuring that your blodd pressure is low. Let's take diabetes ... the symptoms are problems with eyes, dizzines, ... The biomarker is the measure they do with your blood.

I'm a big proponent of focusing on biomarkers and etiology. The medical establishment focused on symptoms (and not even all of the symptoms) for a hundred years and look where we are now re: cure -- not very close.

I think studies like MJFF's PPMI will bring us valuable and treatable biomarker information that will ultimately lead to etiology and cure.

Thanks for your replies.

Diego24, your simple example illustrates the point well. You mention a condition of "low blood pressure" and go on to point out that "The biomarker is measuring that your blodd [sic] pressure is low". By defining the disease in terms of a body state appears to make it easy to identify the biomarker. But wait. You describe the symptom as "feeling dizzy if you get out of your chair". This could be postural hypotension: a failure of the body to automatically return blood pressure to normal. From this perspective we can see that blood pressure alone would not be a sufficient biomarker. Of course, the next step would be to ask what causes the postural hypotension. This can be a symptom of Parkinson's Disease.

indigogo, I too support the search for biomarkers, but I also see a role for objective symptom based tests. For instance, I find the work of Little very interesting. He has a computer system that analyses voice recordings to diagnose and measure the progression of PD.

John