[Ronhutton]

A report in a British newspaper, entitled "Parkinson's pair Walk Again", describes two women who have been given a new treatment. Both have had an operation to fit tubes through which, levodopa is pumped directly into the BOWEL!!! Both were wheelchair bound, and both are now walking normally.
The tube is connected to a pump, worn on the waist, that supplies a steady stream of levodopa through the day.The system, made by a Belgian firm, costs $52,000 per year!! The article states the system is only suitable for those who have not responded to other treatments. It is estimated that about 1,000 people with PD in the UK could benefit from the treatment.
The levodopa bypasses the stomach. I am no medic, and I don't understand how it gets to the brain. Any ideas??
Ron

[aftermathman]

this is also called Duodopa, do a search on that for lots of info.

Aftermathman.

[Stitcher]

Parkinson's pair walk again after drug switch
http://neurotalk.psychcentral.com/sh...ad.php?t=12478

This full article is here.

[paula_w]

A phase III trial is coming to the U.S. in a few months. I called on this one as there are two locations in Florida, and I am very interested. My thyroid may disqualify me but I'm still encouraged that it is a Phase III trial.

From the PDPipeline database: Duodopa

Treatment Information
Treatment Name Duodopa
Symptoms Addressed Balance Bradykinesia Cognitive Problems
Treats general (not specified) PD symptoms Tremor

Trial Type
Treatment of Motor Symptoms

Trial Type Notes
As of January 2007, U.S. phase III clinical trial is planned, but recruitment has not started. (clinicaltrials.gov) A call was made in Jan. 2007 to the recruitment contact number. Advised to call back "in a few months."

Treatment Class Levodopa

Treatment Description "Treatment based on continuous dopaminergic stimulation by means of a formulation of levodopa and carbidopa, dispersed as a viscous gel. Using a patient-operated portable pump, the drug is continuously delivered via a tube directly into the upper small intestine, where it is rapidly absorbed. This delivery system ensures a more even supply and uptake compared with the conventional combination of tablet treatment." (Solvay web site)

Intended for people in late stages of Parkinson's.

Foreign Market Info DUODOPA is authorized for "treating advanced Parkinson’s disease in 28 European countries - Sweden, Austria, Germany, Denmark, Spain, Finland, France, The Netherlands, Norway, Portugal, Belgium, Greece, Ireland, Italy, United Kingdom, Cyprus, Czech Republic, Estonia, Hungary, Iceland, Liechtenstein, Lithuania, Luxembourg, Latvia, Malta, Poland, Slovenia, and Slovakia." Received orphan drug status (press release 12/05)

Treatment Status In Clinical Trials (Outside US)
Recruiting Status (For current trial recruitment information see PDTrials.org )Trial is not recruiting Patients

Comments NeoPharma was acquired by Solvay Pharmaceuticals in Jan. 2005.

Phase IV trials are underway in Sweden and Norway. They are recruiting patients in Sweden for Phase IV study of "Continuous Delivery of Levodopa in Patients With Advanced Idiopathic Parkinsons Disease - Cost-Benefit."
Trial information available at: http://www.clinicaltrials.gov/ct/show/NCT00272688?order=2 and

in Norway for phase IV trial "DAPHNE (Duodopa in Advanced Parkinson’s: Health Outcomes & Net Economic Impact)."
Trial information available at: http://www.clinicaltrials.gov/ct/sho...der=1Sponsor(s)

Sponsor (click for details) URLPrimary Sponsor
Solvay Pharmaceuticals, Inc. Subsidiary of Solvay SAhttp://www.solvay.com/

There is more info about the clinical trials thus far in the pipeline database.
Paula

[Suffolkchris]

This trial was carried out at a hospital in Norwich, Norfolk in the UK which is just 45 miles from where I live and consequently was covered extensively on our local TV and in the local press. To start with the Levodopa was fed into the digestive system via a tube through the nose and once it was proved to work ok this was substituted for a direct tube feed into the upper bowel.
One of the articles also refered to a recent trial in the USA for Levodopa patches. The basic idea being the same as the tube feed ie, to deliver Levodopa at a steady rate whilst maximising the amount absorbed into the blood stream. I know patches have existed for a while to deliver Agonists but as many of us cannot tolerate these drugs the Levodopa patch development could be excellent news and it is slightly less invasive than a tube into the bowel!!
Oh the joys of PD........

Chris

[rd42]

This may be an ignorant statement, but wouldn't it be cheaper and easier to, well, uh, stick it where the sun don't shine?

I wonder if there would be better absorbtion in the colon than in the stomach?

Robert

[reverett123]

Originally Posted by rd42

This may be an ignorant statement, but wouldn't it be cheaper and easier to, well, uh, stick it where the sun don't shine?

I wonder if there would be better absorbtion in the colon than in the stomach?

Robert

But that is a very good question. If I understand correctly, there are two problems with the stomach: lack of absorption and degradation by enzymes. I am sure that the colon-rectal absoption is good or there would be no suppositories. One might even try an enema vehicle with a crushed tablet. But the controlled release or standard, I wonder? And might there be something that enhanced absorption as well?

[michael7733]

From:


http://www.nutristrategy.com/digestion.htm

Digested molecules of food, water and minerals from the diet, are absorbed from the cavity of the upper small intestine. The absorbed materials cross the mucosa into the blood, and are carried off in the bloodstream to other parts of the body for storage or further chemical change. This process varies with different types of nutrients.

Carbohydrates: An average American adult eats about half a pound of carbohydrate each day. Some of our most common foods contain mostly carbohydrates. Examples are bread, potatoes, pastries, candy, rice, spaghetti, fruits, and vegetables. Many of these foods contain both starch, which can be digested, and fiber, which the body cannot digest.

The digestible carbohydrates are broken into simpler molecules by enzymes in the saliva, in juice produced by the pancreas, and in the lining of the small intestine. Starch is digested in two steps: First, an enzyme in the saliva and pancreatic juice breaks the starch into molecules called maltose; then an enzyme in the lining of the small intestine (maltase) splits the maltose into glucose molecules that can be absorbed into the blood. Glucose is carried through the bloodstream to the liver, where it is stored or used to provide energy for the work of the body.

Table sugar is another carbohydrate that must be digested to be useful. An enzyme in the lining of the small intestine digests table sugar into glucose and fructose, each of which can be absorbed from the intestinal cavity into the blood. Milk contains yet another type of sugar, lactose, which is changed into absorbable molecules by an enzyme called lactase, also found in the intestinal lining.

Protein: Foods such as meat, eggs, and beans consist of large molecules of protein that must be digested by enzymes before they can be used to build and repair body tissues. An enzyme in the juice of the stomach starts the digestion of swallowed protein. Further digestion of the protein is completed in the small intestine. Here, several enzymes from the pancreatic juice and the lining of the intestine carry out the breakdown of huge protein molecules into small molecules called amino acids. These small molecules can be absorbed from the hollow of the small intestine into the blood and then be carried to all parts of the body to build the walls and other parts of cells.

Fats: Fat molecules are a rich source of energy for the body. The first step in digestion of a fat is to dissolve it into the watery content of the intestinal cavity. The bile acids produced by the liver act as natural detergents to dissolve fat in water and allow the enzymes to break the large fat molecules into smaller molecules, some of which are fatty acids and cholesterol. The bile acids combine with the fatty acids and cholesterol and help these molecules to move into the cells of the mucosa. In these cells the small molecules are formed back into large molecules, most of which pass into vessels (called lymphatics) near the intestine. These small vessels carry the reformed fat to the veins of the chest, and the blood carries the fat to storage depots in different parts of the body.

Vitamins: Another important part of our food that is absorbed from the small intestine is the class of chemicals we call vitamins. There are two different types of vitamins, classified by the fluid in which they can be dissolved: water -soluble vitamins (all the B vitamins and vitamin C) and fat-soluble vitamins (vitamins A, D, and K).

Water and Salt: Most of the material absorbed from the cavity of the small intestine is water in which salt is dissolved. The salt and water come from the food and liquid we swallow and the juices secreted by the many digestive glands. In a healthy adult, more than a gallon of water containing over an ounce of salt is absorbed from the intestine every 24 hours.


Why Is Digestion Important?

When we eat such things as bread, meat, and vegetables, they are not in a form that the body can use as nourishment. Our food and drink must be changed into smaller molecules of nutrients before they can be absorbed into the blood and carried to cells throughout the body. Digestion is the process by which food and drink are broken down into their smallest parts so that the body can use them to build and nourish cells and to provide energy.

The digestive system is a series of hollow organs joined in a long, twisting tube from the mouth to the ****. Inside this tube is a lining called the mucosa. In the mouth, stomach, and small intestine, the mucosa contains tiny glands that produce juices to help digest food.

There are also two solid digestive organs, the liver and the pancreas, which produce juices that reach the intestine through small tubes. In addition, parts of other organ systems (for instance, nerves and blood) play a major role in the digestive system.


How Is Food Digested?

Digestion involves the mixing of food, its movement through the digestive tract, and chemical breakdown of the large molecules of food into smaller molecules. Digestion begins in the mouth, when we chew and swallow, and is completed in the small intestine. The chemical process varies somewhat for different kinds of food.

Movement of Food Through the System


• Mouth: Seconds
• Esophagus: Seconds
• Stomach: Up to 3 ˝ hours
• Small Intestine: Minutes
• Large Intestine: Hours

The large, hollow organs of the digestive system contain muscle that enables their walls to move. The movement of organ walls can propel food and liquid and also can mix the contents within each organ. Typical movement of the esophagus, stomach, and intestine is called peristalsis. The action of peristalsis looks like an ocean wave moving through the muscle. The muscle of the organ produces a narrowing and then propels the narrowed portion slowly down the length of the organ. These waves of narrowing push the food and fluid in front of them through each hollow organ.

The first major muscle movement occurs when food or liquid is swallowed. Although we are able to start swallowing by choice, once the swallow begins, it becomes involuntary and proceeds under the control of the nerves.

The esophagus is the organ into which the swallowed food is pushed. It connects the throat above with the stomach below. At the junction of the esophagus and stomach, there is a ringlike valve closing the passage between the two organs. However, as the food approaches the closed ring, the surrounding muscles relax and allow the food to pass.

The food then enters the stomach, which has three mechanical tasks to do. First, the stomach must store the swallowed food and liquid. This requires the muscle of the upper part of the stomach to relax and accept large volumes of swallowed material. The second job is to mix up the food, liquid, and digestive juice produced by the stomach. The lower part of the stomach mixes these materials by its muscle action. The third task of the stomach is to empty its contents slowly into the small intestine.

Several factors affect emptying of the stomach, including the nature of the food (mainly its fat and protein content) and the degree of muscle action of the emptying stomach and the next organ to receive the stomach contents (the small intestine). As the food is digested in the small intestine and dissolved into the juices from the pancreas, liver, and intestine, the contents of the intestine are mixed and pushed forward to allow further digestion.

Finally, all of the digested nutrients are absorbed through the intestinal walls. The waste products of this process include undigested parts of the food, known as fiber, and older cells that have been shed from the mucosa. These materials are propelled into the colon, where they remain, usually for a day or two, until the feces are expelled by a bowel movement.


Production of Digestive Juices

Glands of the digestive system are crucial to the process of digestion. They produce both the juices that break down the food and the hormones that help to control the process.

The glands that act first are in the mouth--the salivary glands. Saliva produced by these glands contains an enzyme that begins to digest the starch from food into smaller molecules.

The next set of digestive glands is in the stomach lining. They produce stomach acid and an enzyme that digests protein. One of the unsolved puzzles of the digestive system is why the acid juice of the stomach does not dissolve the tissue of the stomach itself. In most people, the stomach mucosa is able to resist the juice, although food and other tissues of the body cannot.

After the stomach empties the food and its juice into the small intestine, the juices of two other digestive organs mix with the food to continue the process of digestion. One of these organs is the pancreas. It produces a juice that contains a wide array of enzymes to break down the carbohydrates, fat, and protein in our food. Other enzymes that are active in the process come from glands in the wall of the intestine or even a part of that wall.

The liver produces yet another digestive juice--bile. The bile is stored between meals in the gallbladder. At mealtime, it is squeezed out of the gallbladder into the bile ducts to reach the intestine and mix with the fat in our food. The bile acids dissolve the fat into the watery contents of the intestine, much like detergents that dissolve grease from a frying pan. After the fat is dissolved, it is digested by enzymes from the pancreas and the lining of the intestine.


How Is the Digestive Process Controlled?

Hormone Regulators

A fascinating feature of the digestive system is that it contains its own regulators. The major hormones that control the functions of the digestive system are produced and released by cells in the mucosa of the stomach and small intestine. These hormones are released into the blood of the digestive tract, travel back to the heart and through the arteries, and return to the digestive system, where they stimulate digestive juices and cause organ movement. The hormones that control digestion are gastrin, secretin, and cholecystokinin (CCK):

• Gastrin causes the stomach to produce an acid for dissolving and digesting some foods. It is also necessary for the normal growth of the lining of the stomach, small intestine, and colon.

• Secretin causes the pancreas to send out a digestive juice that is rich in bicarbonate. It stimulates the stomach to produce pepsin, an enzyme that digests protein, and it also stimulates the liver to produce bile.

• CCK causes the pancreas to grow and to produce the enzymes of pancreatic juice, and it causes the gallbladder to empty.

Nerve Regulators

Two types of nerves help to control the action of the digestive system. Extrinsic (outside) nerves come to the digestive organs from the unconscious part of the brain or from the spinal cord. They release a chemical called acetylcholine and another called adrenaline. Acetylcholine causes the muscle of the digestive organs to squeeze with more force and increase the "push" of food and juice through the digestive tract. Acetylcholine also causes the stomach and pancreas to produce more digestive juice. Adrenaline relaxes the muscle of the stomach and intestine and decreases the flow of blood to these organs.

Even more important, though, are the intrinsic (inside) nerves, which make up a very dense network embedded in the walls of the esophagus, stomach, small intestine, and colon. The intrinsic nerves are triggered to act when the walls of the hollow organs are stretched by food. They release many different substances that speed up or delay the movement of food and the production of juices by the digestive organs.

Source: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health.

That is probably much more than you wanted to know , Ron, but there it is.

michael b.