All - I learned about this at PAN in February. I've been taking it for two months now. No cure yet - but I am giving it time. Hope is alive.

Jean
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http://www.eurekalert.org/pub_releas...-nfd060707.php

Drug slows and may halt Parkinson's disease

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.


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To reach D. James Surmeier on Saturday and Sunday please call his cell phone at 773-844-1057.

Wow, the cells adapted in just a few hours? Amazing!

I take high BP medication. Maybe I can switch to isradipine.

Thanks alot for posting this.

Article about side effects:

http://content.onlinejacc.org/cgi/reprint/31/4/809

~Zucchini

Hi Jean,
I hope your getting the real thing and not a placebo. Do you have high BP normally? How would this drug effect a pwp that didn't have high BP? What is the dosage you take? If it does work for you will they have you reduce your Parkinson's meds? Do you know if they are still taking people for the trial? Its nice to see some positive research being done on people not mice.
jerry

Or are you taking it "off label"?

I have Geraldo's questions too.

Robert

Jerry & Robert,

I do have mild hypertension. So after i heard about this at the PAN Forum in February, I contacted my neurologist (a lovely and caring person). I sent her the info and asked her if she would prescribe this for me. She said she would.

I've been taking it about 2 months now. No cure for me yet (though - i am ever hopeful). No change in my symptoms. My other meds remain the same.

This is not in clinical trial - just one parkie with mild hypertension hoping that this will work for her like it works on rats! I'm going to stick with this for a year.

I guess you could say I'm taking it off label for PD but 'as directed' for hypertension. I do not know how it would affect someone who does not have hypertension.

best,

Jean,
So, your another W/R. I have found that isradipine is made in several strengths from 2mg to 10mg/er. Just for the sake of science in true w/r form,would you share what dosage are you taking and what are your PD meds and dosage?
jerry

(What does W/R mean?)

My PD meds:

Isradipine 2.5mg capsule 2X day
Mirapex .25mg 2X day
Stalevo 100 2X day
Azilect 1.0 1X day

Best,

jean,
Thanks for the med info. W/R was my attempt at short hand for what many on this forum refer to someone who is willing to test various unused drugs (off label) or supplements on themselves for the benefit of others-----WHITE RATS. Hope I didn't offend------
jerry

Jerry,

No offense taken!!

I've been an offficial W/R in several clinical trials (5 or 6 - can't remember). I accept the label of W/R with pride since only 1% of PWP actually participate in clinical trials. (I think the same few of us keep on signing up - LOL )

Anyway I'm always on the lookout for a supplement or SOMETHING to help beat this disease!!

best,

How interesting that this picture is so rosy!!

In 2006 almost all plans offered coverage during the "donut hole" period. When open enrollment began in November 2006 for the plan year 2007, I couldn't find a single plan in my neck of the woods that covered more than generics in the "donut hole" period.

I hit the hole the first of May. My out of pocket cost went from $174.78 to $608.76 per month. So, I have cut my antidepressant in half...cost cutting $295 to $145. That is all the cost cutting I could do. I have a total of three meds that are brand. Two of them my respective doctors refuse to change to a generic and the third is my insulin. Insulin is not available in generic.

And it does become a matter of whether to pay a bill...like electricity...or buy a medication. Goodness...pay the electric bill...take your thyroid hormone every other day...60 days for the price of 30 days, who knew!!

I look forward to this same analysis to be done with the data for 2007 is in and can be written about.

Part D is a joke to ANYONE who have multiple health conditions and/or serious health condition; e.g. Parkinson's patients.

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The Incredible Shrinking Donut Hole

The number of Medicare Part D subscribers who fall into the coverage gap looks smaller than was feared.
Will that fact fall into the gap inside the Beltway?

Jun 1, 2007
By: Walter Armstrong
Pharmaceutical Executive
http://www.pharmexec.com/pharmexec/a...29161&pageID=2

Medicare Part D's infamous donut hole—the gap in coverage where subscribers have to shell out full drug costs—sparked a national debate long before the first poor, frail, creaky (or so you imagine) senior citizen stumbled into it. Critics of Part D—mostly Democrats, plus advocates ranging from AARP to the Gray Panthers—argue that government price negotiations, which the legislation bans, would lead to savings that could close the gap. Part D backers—mostly Republicans and PhRMA—counter with "Don't fix it if it ain't broke," pointing to surveys showing that as many as 80 percent of the 23 million subscribers are pleased with the program after just the first year. Plus, they say, Part D's so-called consumer-driven design controls costs, which, in fact, came in lower than projected.

The media has binged on the donut hole, running countless stories about seniors with serious medical conditions who were unable to afford their prescriptions and had to stop taking them, say, or choose buying pills over paying electric bills. Understandably, seniors, doctors, and caregivers have all been frightened, confused, and angered. When advocates declared a National Medicare Part D "Donut Hole Day" last September 22—the date when the "average" beneficiary would hit the $2,250 limit and therefore fall into the gap—golden-years grassrooters turned out in full force. They picketed PhRMA offices chanting "Pharma got the donut, we got the hole," marched on statehouses, and held an "Eliminate the donut hole" action, during which some 70,000 little pastries were eaten, crushed, thrown, and otherwise destroyed.

Needless to say, squaring an uprising of oldsters with that 80 percent pleased-with-Part-D statistic is more than just a math problem. With Part D a work in progress, it has been all too easy to size the donut hole to any agenda's needs. For example, AARP, after only six months, was agitating that between 24 percent and 38 percent of enrollees were hitting the hole. But by September, America's Health Insurance Plans (AHIP) member organizations were reporting a modest 10 percent. Meanwhile, individual insurance plans keep floating much higher figures—by deceptively including the most vulnerable Part Ders, the 30 percent of low-subsidy enrollees who are, in fact, protected from loss of coverage.

But now that first-year data are in, it's possible to check the gap against reality. A new study conducted for PhRMA by the Amundsen Group, a consulting firm based in Lexington, Mass., reports that 12.6 percent of all Part D beneficiaries got donut-holed in 2006. That's about 2.8 million seniors—many of whom presumably have significant health problems—and no matter what your position or politics, that situation has to give you pause.

Still, a closer analysis reveals a less troubling landscape. Amundsen found, after combing through 86 million Part D transactions extracted from Verispan's anonymous patient-level pharmacy database, that the actual number of Part D beneficiaries who ended up paying full price for their meds once in the gap was 4.6 percent. The remaining 8 percent had plans that provided complete or partial gap coverage—or "wraps" from past employers, or some other prescription insurance. In addition, fewer than half of these out-of-pocket payers ended up forking over more than $1,000, and only 0.8 percent of all Part Ders had to come up with the full $3,600, after which catastrophic coverage kicked in.

It should be noted that other analysts are coming up with other, often higher percentages of enrollees falling into the gap. And according to Amundsen, the percentage of seniors paying full price is likely to inch up to slightly more than 6 percent this year, since many of 2006 Part Ders signed up late and didn't have 12 months of drug spend.

Whether reality will resonate inside the Beltway is an open question. At press time, the Senate had voted down any move to overturn the ban on price negotiations, while the House had passed legislation requiring them. The shadow of a Bush veto hung over the exercise. Both sides have their points, but the only thing they seem to agree on is that keeping a polarizing issue alive is in every pol's best interest. With the 2008 campaign starting yesterday, rhetoric pitting "price controls" against "sick seniors" is rich enough to sink your teeth into.