Isradipine Phase II Trials for Parkinson's Disease

Professor D. James Surmeier's exciting work investigating the relationship between calcium and sodium channel modulation and Parkinson's disease has been widely known in the Parkinson's community since his June 2007 article in Nature. The article described how isradipine restores older dopamine neurons to their youthful condition. In it Dr Surmeier describes how he feels that people may be able to take isradapine to protect brain cells from Parkinson's like they now take baby aspirin for their hearts. He also hopes that Isradipine can extend by two to three times the therapeutic window that patients have to continue taking L-DOPA before it loses its effectiveness or starts to have serious side effects.

A small clinical trial has been completed at Northwestern University proving the safely and tolerance of Isradipine in PD patients. The phase II trial, Safety and Tolerability of Isradipine (a potential neuroprotective agent) in Patients with Parkinson's Disease - Stage II is still in recruitment. (see: below)

With funding from the Michael J. Fox Foundation Dr Surmeier is now working with fellow Northwestern chemistry professor Dr Richard Silverman to develop a new drug (calcium channel blocker) that will just target one of the two calcium ion channels, Cav1.3 L-type calcium channel antagonist to slow or stop progression of the disease. Success could bring a patent and marketing by a major drug company.

Source: http://www.michaeljfox.org/research_MJFFfundingPortfolio_searchableAwardedGrants_3.cfm?ID=492

Full text of clinical trial: http://clinicaltrials.gov/ct2/show/NCT00753636

How the Buteyko Method Is Said to Work

The Buteyko Hypoventilation Technique was designed for people with asthma but it can work for Parkinson's too.
Breathing Basics
The trigger for breathing is the amount of carbon dioxide (CO2) in the blood. No, not the oxygen level, the CO2 level. Under normal circumstances when the carbon dioxide levels in your bloodstream rise, you exhale to make room to replace some of that carbon dioxide with oxygen and bring the CO2 levels back to normal.

If you were having an asthma attack and in panic mode, you would probably be breathing too quickly. In this over-breathing state your would be taking in a much larger volume of air (oxygen) than normally. Too much oxygen causes the CO2 levels to drop - not rise as you might think. So the reaction of the body is to restrict the airways into the lungs to reduce the amount of air inhaled...and this creates more panic and more over-breathing.

Based upon the principle that the symptom of asthma breathing is having too much oxygen and having too little carbon dioxide in the blood, the Butyeko technique was designed to break the negative feedback cycle of panic-overbreathing-panic-overbreathing. It teaches the body to breathe more shallowly: decreasing the volume of air reaching the lungs on each inhalation. The method is to train the body to tolerate a higher concentration of CO2 in the bloodstream as well.

What about PD?
Okay, you have Parkinson's disease or any neuromuscular disease and not asthma. What does this mean to you? Muscle stiffness, loss of elasticity and weakness in the respiratory muscles may already restrict your airways and cause the swallowing, choking and breathing issues symptomatic in PD. You may already be doing shallow breathing and retaining too much CO2. You may be over-breathing without realizing it.

Now this raises some questions/issues
Is there a danger of an excessive amount of CO2 in the bloodstream?

CO2 levels in the bloodstream reflect the acid status of your blood. Low levels can be due to increased acidity from diabetes, kidney disease, metabolic disorders or chronic hyperventilation. Most of the CO2 in the body is in the form of bicarbonate or hydrogen carbonate (HCO3-) The bicarbonate function is to maintain the pH balance from being neither too acidic nor too basic. The usual result of an increased amount of dissolved CO2 is acidosis or respiratory acidosis if the lung function is diminished.

Carbon dioxide retention can result in hypercapnia when too little CO2 is removed from the blood by the lungs. The early symptoms of hypercapnia include flush, muscle twitches, "hand flaps" (similar to autistic hand flapping,) reduced neural activity and possibly elevated blood pressure.

Diaphragmatic fatigue can also lead to hypoventilation. Ventilation is not adequate to conduct the gas exchange. This can occur when carbon dioxide retention impairs the ability of the diaphragm to properly contract...and expand...which impairs the ability of the body to exhale and inhale.

Response
The Butekyo method seeks to get the patient used to higher carbon dioxide levels to address breathing issues; to train the body not to respond to these levels. The concept is to break into the "negative feedback cycle" by teaching shallower breathing. In addition, the theory is that asthma preventers and inhalers mask the natural self defensive behaviour of the body. Moreover the meds may actually make it harder for the body to react naturally (shallow breathing) during the next attack...

How does this technique apply to sleep disorders?
Since poor breathing patterns can lead to poor sleep, let's take a minute to touch on sleep apnea or sleep aponea depending upon your country of origin. Many people suffer from sleep apnea for years without even being aware. Because the Butekyo Method might assist in eliminating this aspect of sleeping disorder, here are some signs of the problem: Snoring, restlessness or excessive movement such as kicking while asleep, mouth breathing rather than nose breathing, thirst during the night or upon waking, dry mouth, waking but still tired - feeling unrefreshed, being breathless when exercising, falling asleep while watching TV or in meetings or social occasions. And of course the apneas themselves when you literally cease breathing.

Normal sleep would transition through five stages with the final being REM sleep. If you are not breathing properly, if you are hyperventilating - over-breathing - you will remain in the light sleep of stages 1 and 2 while never reaching the most restful 3 and 4 stages and certainly not REM (rapid eye movement) sleep.

You can be aided by any of the breathing methods discussed in previous articles, if you are exhibiting any over-breathing symptoms above, take some time to review Breathing Exercises for PD parts I-III again as well as the Yoga exercises/poses to aid relaxation

Breathing Exercises for PD: Yoga and Buteyko - Part III

Pranayama

Yogic breathing involves abdominal (diaphragm) breathing, intercostal (rib cage) breathing, and clavicular (collar bone-shoulders) breathing.

We've concentrated on getting the diaphragm involved in the breathing pattern because many Parkinson's patients don't use their diaphragms much. It is the diaphragm which is so vital to allowing the lungs to expand to inhale. Even more important is its role in the exhale, forcing out as much of the old air, clearing the lungs to make room for fresh air.

It is always a good practice to stretch your spine before breathing exercises.

Stretching first adjusts posture and opens the chest area

In Yoga the focus is on the exhale. It is the respiratory equivalent of clearing the palette in order to better taste the next course, the inhalation.  I would like to add that on the inhale you begin to allow yourself to relax, althought the tension will not leave your neck and shoulders until the exhale.

Pranayama is the aspect of Yoga or Hatha Yoga devoted to breathing. Prana is breath (vital energy in the body) and Yama means control. It is one of the five principles of Yoga.

According to Pranayama:
Inhalation stimulates-revitalizes the system-fills the lungs.
Retention raises the internal temperature and increases the absorption of oxygen
Exhalation allows the diaphragm to return to a normal position which helps the rib cage to contract, expelling impurities.

One of the problems with not breathing "properly" is that we go into panic mode which often traps air in the lungs, a condition known as hyperinflation. To fight this we try to breathe faster possibly gulping for air which results in more inflation and more trapped toxic air. We feel worse, not better - causing more panic and the vicious cycle worsens. Yoga is not just the body, the exercises are to help you find a better place - to release the fear. Close your eyes, exhale, be the exhale.

If you are not using soothing music, you can clear your head or find a peaceful image which allows you to be...

From Hatha Yoga - The Exhale - Diaphragm, Rib Cage, Upper Thoracic/Clavicular
Although most effectively performed when you are prone, you can also remain seated.

1) Empty the lungs as much as possible.
2) Slowly lower the diaphragm allowing air to enter the lungs.
Once the abdominal area swells filling the bottom of the lungs with air...
3) Expand the ribs without straining, then
4) Allow the lungs to completely fill by raising the collar-bones
The entire process is smooth and silent, no pauses, no noise
5) The exhale is the same sequence allowing
6) The diaphragm now forces the air from the lungs
7) As the rib cage contracts
8) And the chest naturally falls back in on itself

We will explore utilizing Pranayama for depression on another day.
Meanwhile, remember that Yoga breathing exercises are also helpful for Parkinson's constipation

The Buteyko Method was originally designed to help control asthma as well as other breathing disorders. While not everyone will benefit, it is said that at least 50% will.

The Control Pause Breathing Test
Take 2 normal breaths
Exhale
And then see how long you can Hold Your Breath.
The goal is 60 seconds.

Helpful hint: if your nasal passages are blocked, try pinching your nostrils together for a few seconds. If that doesn't work, try gently pinching above the bridge of your nose (top of the eye sockets) with the thumb and middle finger of one hand while pressing the depression above your lips/below your nose. Gently hold. Release. Repeat.

Shallow BreathingBreathe through your nose - only your nose - for 5 minutes
Take shallow breaths - keep your mouth shut
Then take the Control Pause Breathing Test again to see if you have improved.

Put it Together
Repeat the Test - Shallow Breath - Test sequence 4 or 5 times in a row.
Repeat this training session 3 or 4 times a day - every day for a week.
You may miss a session here or there, don't worry about it.
The goal is to increase your Control Pause

After a week you should be able to exhale and hold your breath for at least a 60 second count.

9-19-2011 Addendum
If you need additional help for developing breath stamina:

Respiratory Muscle Strength Trainer, a simple hand-held device looking very much like a large whistle. Regular use should help improve the strength of the muscles used to inhale and exhale.

Dancing Away the Parkinson's Shuffle

Join the Dance of  PD Neuroprotection

An inovativative program of the Brooklyn Parkinson Group and the Mark Morris Dance Center, Fort Greene, Broolyn has been bringing together professional dancers and people with Parkinson's Disease since 2001.

The first of its kind, the program was initated by Olie Westheimer, founder of the Brooklyn Parkinson Group, because she believed that dancing could improve the lives of patients treated by her husband, Dr Ivan Bodis-Wollner a medical expert on Parkinson's. He has said that "movement like dance exercise seems to be neuroprotective."

Patients wait for the class to begin in a spacious, brightly lit studio with their canes, wheelchairs and walkers. That don't look ready to dance but they are. Parkinson's patients, it turns out, can dance better than they can walk.

To see for yourself, take a look at this Mark Morris Dance Group website where you can read, see photos and watch the videos - this is good stuff:

Did you notice that there are chair exercises which involve the entire body? I was excited to see that some dancers did not have to adopt that wider standing stance for balance. They must have already integrated sighting for balance into those exercise. You can see improved coordination from the rhythmic movement.

Dance for PD is an outreach collaboration between the Brooklyn Parkinson Group, a chapter of the National Parkinson Foundation and the Morris Dance Group. Classes are provided weekly not only can people with PD attend but also their caregivers.

The classes led by professionally trained dancers teach using dance exercises which addresses not only balance, muscle stretching and strengthening but also how the dancer incorporates hearing the music with imagination, touch and sight to contol movement. What they don't have to teach is the joyful release which dancing can bring.

The Mark Morris Group has made their services available on the west coast, in Canada and the UK. Plans are underway for more PD dance training workshops.

additional resources:
From NPR: Parkinson's Patients Find Grace in Dance
Parkinson's and dance: An Unusual partnership unites
Dance for Parkinson's Disease Comes to Bay Area written after this post