Test drug seen as best hope in decades for tackling Parkinson's

http://nationmultimedia.com:80/world...ewsid=30036474

PARIS - A drug tested on lab mice slows and may even halt the progress of Parkinson's, offering the brightest pharmacological hope in decades of rolling back this tragic disease, US researchers report on Sunday.

Isradipine, already licensed for treatment for high blood pressure, rejuvenated ageing dopamine cells, the brain cells whose death causes Parkinson's, they say.

The outcome among mice was so promising that the team now plan on conducting trials on human volunteers.

"Our hope is that this drug will protect dopamine neurons, so that if you began taking it early enough, you won't get Parkinson's disease, even if you were at risk," said lead researcher James Surmeier, professor of physiology at Northwestern University in Chicago.

"It would be like taking a baby aspirin every day to protect your heart."

Parkinson's is an incurable, degenerative disease of the central nervous system that causes uncontrollable shaking, along with impaired speech and movement. In approximately one third of cases it also results in dementia.

Estimates of its prevalence vary between 0.1 and 0.3 per cent of the population, meaning that approximately one in 500 people contract the disease.

The cause is a loss of dopamine, a chemical messenger that helps direct movement. The substance is provided in a part of the brain called the substantia nigra.

Most pacemaking neurons use sodium ions to produce a regular electrical signal.

But the new research unexpectedly found that dopamine cells, when they reached adulthood, start to depend more and more on calcium ions.

This discovery is important, because calcium ions are far more troublesome to control than their placid sodium counterparts: the cell uses up lots of energy, either to round up and sequester the calcium or pump it out.

As a result, the dopamine cells become stressed on reaching their calcium-addicted adulthood and die prematurely.

Surmeier's hunch was to try isradipine, a well-tolerated hypertension and stroke drug commercialised under the name of DynaCirc, which blocks the channels in the cell surface that admit calcium.

Tested on lab-dish cells and then on mice which had been genetically engineered to have Parkinson's, the team found that within a few hours of being exposed to the drug, the neurons reverted to their youth-like state, of using sodium.

This lowered the cells' stress level, making them less vulnerable to the toxins, still poorly understood, that kills them.

"They start acting like they're youngsters again," Northwestern quoted Surmeier as saying.

The study is published online on Sunday by Nature, the British science journal.

So far the work has only been carried out on animals, and more needs to be done to assess the drug's effect on humans.

But Surmeier voiced cautious hopes it could be the first treatment to prevent or slow the progression of this devastating disease.

The mainstay treatment for Parkinson's is L-DOPA, a drug that the brain converts into dopamine.

At first, L-DOPA has a seemingly miraculous effective on symptoms. The problem, though, is that it becomes less and less effective as time wears on and the disease progresses. That forces doctors to raise the dose of this drug, which induces unwanted side-effects, including spastic, jerky movements.

So, if isradipine can slow the death of dopamine neurons, the L-DOPA "honeymoon" could be significantly extended.

"If we could double or triple the therapeutic window for L-DOPA, it would be a huge advance," said Surmeier. "There has not been a major advance in the pharmacological management of Parkinson's in 30 years."

Agence France-Presse

"Metatone is an oral suspension of Vitamin B1, calcium glycerophosphate, potassium glycerophosphate, sodium glycerophosphate, and manganese glycerophosphate. " -Wikipedia

Now read this part again...

"Most pacemaking neurons use sodium ions to produce a regular electrical signal.

But the new research unexpectedly found that dopamine cells, when they reached adulthood, start to depend more and more on calcium ions.

This discovery is important, because calcium ions are far more troublesome to control than their placid sodium counterparts: the cell uses up lots of energy, either to round up and sequester the calcium or pump it out.

As a result, the dopamine cells become stressed on reaching their calcium-addicted adulthood and die prematurely."

refresh my memory rick

metatone?

where do u get this?

mary

Is metatone a calcium antagonist? I don't get it.

On 1st June, I posted,
"The important thing is all the data points in the same direction. I have looked for substances that reduce the permeability of the BBB, and have found that statins and hypertension drugs (high blood pressure) reduce the permeability. Do they also improve PD symptons?? I have some evidence that hypertension drugs do reduce symptons. "
In http://www.eurekalert.org/pub_releas...-nfd060707.php, it says,
"isradipine, a drug widely used for hypertension"
I know a PWP who was diagnosed 20 years ago, has been taking hypertension drugs for those 20 years, and has never needed any PD meds.
The next question is does Isradipine reduce the permeability of the blood-brain barrier???
Ron

steffi's thread can be found at http://neurotalk.psychcentral.com/sh...light=metatone

I did a little work on Medline and the minerals in the tonic play a big role in the health of the BBB. So, if one has a problem absorbing or otherwise handling these electrolytes then one is getting a double whammy of BBB problems causing longterm problems and ion channel disruption causing today's symptoms. If so, then steffi gets her garden trowel and terrorizes the countryside because her cellular systems benefit from the flood of electrolytes as did the fellow taking the penicillin with potassium added.

Does it make sense?

Ron,

Isradipine was mentioned at the PAN forum in February. This calcium channel blocker was shown to block calcium in dopamine-producing cells (in rats), thus reducing stress, and eventually the cells started producing dopamine again.

So I came home from PAN and contacted my doctor. She agreed to start me on isradipine. I've been on it for 2 months now - nothing miraculous to report. But I'll be patient and see how I am in 6 months - 9 months - 12 months.

So what has happened in the meantime?

Robert Bert

Robert,

i still take dynacirc cr -- nearly 3 years and counting. does it work? no idea. but it's been quite a while since i've had to adjust my meds - maybe 2 years? my progression is slow.

i plan to write to dr surmeier and tell him - plus let him know that I have had 4 spect scans and maybe they would be helpful to him even though i'm not in a controlled study.

jean

am confused--I thought increased BBB permeability was not desirable--in fact was instrumental in development of PD. are you discussing selective BBB permeability increases? and how is that ensured?
If a "defective" BBB is etiopathologic in parkinson's, how does increasing its permeability help? I am aware with this antihypertensive drug, permeability to calcium is the affected--though blockage of calcium channels does not imply increased BBB permeability to this element . thanks, madelyn