[reverett123]

Some of you may remember the postings of Anne Frobert, the French MD and PWP who was experimenting with banding. She and I have been collaborating for about six months now to draw together four years of her work into a comprehensive picture of PD. And I really think she has managed to work it out. I am going to post various components of this complex picture over the coming weeks but, to avoid overwhelming everyone on the subject, I will try to do it in a more or less orderly fashion. The reason I am introducing this thread at this time is to make the point that the various threads that have sprung up are not mutually exclusive. They may all be right.

This relatively new way of looking at PD (and maybe other diseases as well) has been called the Multi Hits Theory and is an important departure from the previous thinking. It is complex but its very complexity opens up new avenues of treatment.

To introduce this new way of looking at PD and how it differs from the present approach, I use two analogies. Please bear with me because it is the type of thing that, while the details are complex, the overview is simple. But I need to practice these analogies.

The Old Way: We all live in a deep valley beside the Parkinson's River. It is a mighty river and no one knows where it begins but there are stories of a great spring at the foot of the mountain far up the valley. Some say it is called Mercury. Others Aluminum, Genetics, Pesticides, etc. All we really know is that the river floods and washes away our lives. There is much talk of going somewhere up the valley and digging a canal to carry the flood away, but the river is so strong and the valley so deep that every attempt has failed.

The New Way: Again, we live in a valley, river, yada yada. But in this analogy the valley floor is broad and the river flows through a vast marsh where we all live. Exploring this marsh we find that all around the head of the valley numerous small springs emerge and their streams meander down the valley floor. The springs have various names - Aluminum, Genetics, yada yada. Their waters flow lazily, looping back and forth, sometimes intersecting and then parting, some running long distances alone, but all ultimately converging on the river channel. There is flooding here, too, but depending on where one lives in relation to the various streams, some are washed away very often while others live long lives with few problems. The tribal leaders agree that this should be dealt with and send explorers out. They find that there are places where the valley wall is low enough and the individual streams small enough, that several small canals are feasible to carry the floods harmlessly away.

I'm sorry if this seems obvious. But the entire research community, with a few hardy exceptions, seems to be intent on finding that one darned spring to dig that one darn canal. While we are getting washed away.

This view answers many questions, such as why we are so individualized. And why so many different explanations seem to fit or to fit almost. And like the marshy valley, there are critical points where intervention can make a big difference. Control of inflammation and stress are two easy ones and there are at least half-a-dozen others. If more of the scientific effort can be directed away from the search for a single magic bullet toward this broader view the results could be dramatic.

[paula_w]

Rick i think the pd community is leaning toward multiple causes of PD, while at the same time recognizing similarities in treatment options with other neuro illnesses. This is especially true of delivery systems, which have everything to do with the BBB.

I can't remember where I post what anymore so sorry if this is a repeat. i fear that information is being multiplied at such a manic rate, that treatment options will always lag way behind what we learn. [well this is a given]

That's why it is imperative to do more than chase the ultimate cure [s]and stop and take care of people along the way. Everything isn't a cure, but it can come close and much can be learned by its use on people.

Everything boils down to the expense. It should be boiling down to what prevents human suffering.

An article in the New York Times this week said avoid patient anecdotal information posted [funny that it said posted], in learning to understand your doctor. I can see the need to use good judgement about what you read, but the attitude behind that statement promotes the continuation of viewing the patient as inferior and subjected to the moods of medical personnel.

If a new "campaign" is being launched to regain the respect and control of doctors, it will only be as successful as the respect is returned by the doctors. Some patients may be medically illiterate, but a literate one can smell patronizing a mile away.

I'm ranting, yes, that article ruffled my feathers. What's my point? There are multiple causes, delivery systems, drugs, [some that already work] being withheld from patients, which is devastating their lives. A new report is coming out soon with stories of many patients whose lives were ruined by companies halting drugs. GDNF was hardly the first or only one.

This is what it boils down to in the end....a bio tech deciding to spend money on us. Unless....somebody finds it unexpectedly. And once again, GNDF rears up as a solution, being on the list to tighten the BBB, as well a s on the list of what can regenerate neurons. Logically, it would be used until something better comes along, so pd patients don't suffer.

I'll never stop driving this point home.
just ignore this and carry on...

paula

[burckle]

Never heard of the Many Hits Theory. Is there a reference? Can't find it on the Internet. Perhaps you mean The Multiple Working Hypothesis which was first expounded on by T. C. Chamberlin toward the end of the 19th century and has been a staple of scientific thinking since early in the 20th century.

Lloyd

[reverett123]

...here is a recent varient. I've also seen "multi factoral" used.

1: Cell Transplant. 2006;15(3):239-50.

Progressive dopamine neuron loss in Parkinson's disease: the multiple hit
hypothesis.

Carvey PM, Punati A, Newman MB.

Department of Pharmacology, Rush University Medical Center, Chicago, IL 60612,
USA. pcarvey@rush.edu

Animal models have been an essential tool for researchers and clinicians in
their efforts to study and treat Parkinson's disease (PD). Thus, the various
ways 6-hydroxydopamine is employed, the use of MPTP in rodents and nonhuman
primates, the prenatal exposure to bacterial endotoxin, the postnatal exposure
to environmental toxins such as paraquat and rotenone, the assessment of
dopamine (DA) neurons in genetic knockout mouse, and even the behavioral
analysis of fruit flies and worms have added significantly to our knowledge base
of PD--or have they? Are these animal models manifesting a true model of PD?
Have the 7786 published studies (to date) on PD with animal models led to a
clearer understanding of its etiology, treatment, or progression? In this review
we critically assess this question. We begin with a succinct history of the
major contributions, which have led to the current animal models of PD. We then
evaluate the primary issue of the progressive loss of DA neurons, which, except
for a few studies, has not been addressed in animal models of PD, even though
this is the major pathological characteristic of the disease. Lastly, we discuss
the possibility that more than one risk factor for PD may be necessary to
develop an animal model that shows synergy--the progressive loss of DA neurons.
Thus, the multiple hit hypothesis of PD-that is, the effect of more then one
risk factor-may be the start of new era in animal models of PD that is one step
closer to mimicking the pathology of PD in humans.

PMID: 16719059 [PubMed - indexed for MEDLINE]