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.

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

Drug slows and may halt Parkinson's disease
http://www.eurekalert.org/pub_releas...-nfd060707.php
CHICAGO --- Northwestern University researchers have discovered a drug
that slows - and may even halt - the progression of Parkinson's
disease. The drug rejuvenates aging dopamine cells, whose death in the
brain causes the symptoms of this devastating and widespread disease.
D. James Surmeier, the Nathan Smith Davis Professor and chair of
physiology at Northwestern University's Feinberg School of Medicine,
and his team of researchers have found that isradipine, a drug widely
used for hypertension and stroke, restores stressed-out dopamine
neurons to their vigorous younger selves. The study is described in a
feature article in the international journal Nature, which will be
published on-line June 10.
Dopamine is a critical chemical messenger in the brain that affects a
person's ability to direct his movements. In Parkinson's disease, the
neurons that release dopamine die, causing movement to become more and
more difficult.
Ultimately, a person loses the ability to walk, talk or pick up a
glass of water. The illness is the second most common
neurodegenenerative disease in the country, affecting about 1 million
people. The incidence of Parkinson's disease increases with age,
soaring after age 60.
"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 Surmeier, who heads the Morris K.
Udall Center of Excellence for Parkinson's Disease Research at
Northwestern. "It would be like taking a baby aspirin everyday to
protect your heart."
Isradipine may also significantly benefit people who already have
Parkinson's disease. In animal models of the disease, Surmeier's team
found the drug protected dopamine neurons from toxins that would
normally kill them by restoring the neurons to a younger state in
which they are less vulnerable.
The principal therapy for Parkinson's disease patients currently is L-
DOPA, which is converted in the brain to dopamine. Although L-DOPA
relieves many symptoms of the disease in its early stages, the drug
becomes less effective over time. As the disease progresses, higher
doses of L-DOPA are required to help patients, leading to unwanted
side-effects that include involuntary movements. The hope is that by
slowing the death of dopamine neurons, isradipine could significantly
extend the time in which L-DOPA works effectively.
"If we could double or triple the therapeutic window for L-DOPA, it
would be a huge advance," Surmeier said.
The work by Surmeier's group is particularly exciting because nothing
is known to prevent or slow the progression of Parkinson's disease.
"There has not been a major advance in the pharmacological management
of Parkinson's disease for 30 years," Surmeier said.
Surmeier, who has researched Parkinson's disease for 20 years, had
long been frustrated because it wasn't known how or why dopamine cells
die in the disease. "It didn't seem like we were making much progress
in spite of intense study on several fronts," he said.
Because he's a physiologist, Surmeier decided to investigate whether
the electrical activity of dopamine neurons might provide a clue to
their vulnerability. All neurons in the brain use electrical signals
to do their job, much like digital computers.
First, Surmeier observed that dopamine neurons are non-stop workers
called pacemakers. They generate regular electrical signals seven days
a week, 24 hours a day, just like pacemaker cells in the heart. This
was already known. But then he probed more deeply and discovered
something very strange about these dopamine neurons.
Most pacemaking neurons use sodium ions (like those found in table
salt) to produce electrical signals. But Surmeier found that adult
dopamine neurons use calcium instead.
Sodium is a mild mannered ion that does its job without causing a whit
of trouble to the cell. Calcium ions, however, are wild and
rambunctious. Remember when Marlon Brando rode into town with his
motorcycle gang in "The Wild One"" Those guys were like calcium ions.
"The reliance upon calcium was a red flag to us," Surmeier said.
Calcium ions need to be chaperoned by the cell almost as soon as they
enter to keep them from causing trouble, he noted. The cell has to
sequester them or keep pumping them out. This takes a lot of energy. "It's a little like having a room full of two year olds you have to
watch like a hawk so they don't get into trouble," Surmeier said.
"That's really going to stress you." With three boys under age eleven,
he can relate to the stressed dopamine neuron.
Surmeier theorized that the non-stop stress on the dopamine neurons
explains why they are more vulnerable to toxins and die at a more
rapid rate as we age.
But these findings still didn't offer him a new therapy.
Then, serendipity struck when he was working on a different problem.
He discovered that young dopamine neurons and adult ones have an
entirely different way of operating.
When the neurons are young, Surmeier found they actually use sodium
ions to do their work. But as the neurons age, they become more and
more dependent on the troublesome calcium and stop using sodium. This
calcium dependence - and the stress it causes the neurons --is what
makes them more vulnerable to death.
What would happen, Surmeier wondered, if he simply blocked the
calcium's route into the adult neuron cells" Would the neurons revert
to their youthful behavior and start using sodium again"
"The cells had put away their old childhood tools in the closet. The
question was if we stopped them from behaving like adults would they
go into the closet and get them out again"" Surmeier asked. "Sure
enough, they did."
When he gave the mice isradipine, it blocked the calcium from entering
the dopamine neuron. At first, the dopamine neurons became silent. But
within a few hours, they had reverted to their childhood ways, once
again using sodium to get their work done.
"This lowers the cells' stress level and makes them much more
resistant to any other insult that's going to come along down the
road. They start acting like they're youngsters again," Surmeier said.
The next step will be launching a clinical study.
"This animal study suggests that calcium channel blockers, drugs
currently used to reduce blood pressure, might someday be used to slow
the steady progression of Parkinson's disease," said Walter J.
Koroshetz, M.D., deputy director of the NINDS.

RONHUTTON,
Could you check with your friend that has PD and takes meds for high bp and find out the active ingredient (isradipine) and dosage for us?
jerry