AMD Update 11 Potential Breakthrough Drug Delivery System for AMD

Earlier last week, I was reading a report on Dr. Robert Langer’s keynote address from the recent ARVO meeting held in Ft. Lauderdale, FL, “The Future of Regenerative Medicine in Ophthalmology”, and thought that his idea of a prototype microchip or polymer implant, that contained pockets or drug reservoirs that could be selectively controlled or opened by a patient’s physician, in this case the individual pocket or drug reservoir opened by the application of a focused laser beam, could really be useful in treating AMD. Instead of monthly injections of anti-VEGF agents, a single implant containing multiple doses could be implanted and each dose activated by a simple ophthalmic laser beam upon need.

Then, lo and behold, last Friday morning I received a news release from a company called On Demand Therapeutics, Inc., which, it turns out, holds the rights from Dr. Langer’s laboratory at MIT and spin-off companies, to develop just such a device. John Santini is the president of the new company. He is the co-founder and former president of MicroCHIPs, a company founded by Santini and Dr. Langer in 1999, to develop proprietary reservoir arrays that are used to store and protect chemical sensors or potent drugs within the body for long periods of time, based on the research and inventions derived from Dr. Langer’s MIT laboratories.

A Little History

In 1976, Dr. Langer and Judah Folkman, MD, a pioneer in anti-angiogenic research, devised a polymer material that released an angiogenic inhibitor. The agent thwarted neovascularization and stunted the growth of tumors in rabbit corneas. The research bore fruit when the U.S. Food and Drug Administration approved the anti-VEGF agents Macugen (pegaptanib sodium solution, Eyetech/Pfizer) in 2004 and Lucentis (ranibizumab, Genentech) in 2006.

Santini, a former graduate assistant of Robert Langer, founded MicroCHIPS along with Langer and MIT colleague Michael Cima in 1999. He led the firm for 11 years, through several funding rounds, including a recent round resulting in nearly $16.5 million raised that took the total to $70 million.

Santini has now moved on to head up On Demand Therapeutics Inc., a San Francisco-based MicroCHIPS spinout.

The Problem and a Possible Solution

In his ARVO address, Dr. Langer said the researchers' main dilemma in developing a drug release reservoir was designing polymers that could elute large bioactive molecules. Porous polymers enable timed and controlled elution of almost any bioactive molecule, regardless of its size. "These pores are large enough so that molecules, even of millions of molecular weight, can get through," according to Dr. Langer.

Newer technologies show promise. For example, a prototype microchip device comprises tiny pockets or drug reservoirs. The application of an electrode dissolves a gold coating on the chip, allowing the drug agent to elute in a timed and controlled way. Such devices are being developed by MicroCHIPS for the treatment of severe osteoporosis through the delivery of an anabolic bone-building hormone, and also for continuous glucose monitoring for people with diabetes.

Dr. Langer said that the chip (or drug reservoirs) may also have applications in retinal drug delivery.

A physician-controlled retinal drug delivery technology would involve an implant with sealed drug reservoirs. The targeted application of an ophthalmic laser to open one or more of the wells to allow the release of the respective drug into the eye, could constitute a breakthrough, said Dr. Langer.

On Demand Therapeutics, Inc. (ODTx)

ODTx was formed in May 2009 as a unique joint venture between MicroCHIPS, a developer of intelligent implant systems, and InterWest Partners, a leading diversified venture capital firm. ODTx leverages the intellectual property and technical expertise of MicroCHIPS combined with the ophthalmic domain expertise and financial resources of InterWest. The company has an exclusive, worldwide license to 60 issued patents and numerous pending applications related to ophthalmic on-demand drug delivery and related technologies.

The ODTx device is a biocompatible, non-resorbable injectable rod, comprised of multiple discrete reservoirs designed to release, on demand, specific drugs in clinically optimized doses. (See Figure 1.) Each reservoir can safely store small or large molecule drugs in the eye until release is initiated using a standard ophthalmic laser during a simple, routine, office-based procedure. (See Figure 2.)

Figure 1. The Drug Reservoir Implant 

Figure 2. Initiation of Drug Release

Typical retinal drug delivery procedures, such as for treating CNV (choirodal neovascularizaion, or “wet” AMD) require monthly intravitreal needle injections. Current implantable devices are largely focused on steroids and/or deliver sustained release formulations which have no mechanism for control of dosing, leading to significant side effects such as glaucoma or cataracts. In contrast, once the ODTx device is implanted during an in-office procedure, the ophthalmologist can control drug delivery by focusing a laser beam on one of the multiple sealed reservoirs.

Administering a laser pulse creates a micro-opening in the device that releases the drug into the eye. Unactivated reservoirs remain intact until those doses are indicated. There is no need for monthly injections and the patient is easily maintained through regular follow-up visits and subsequent non-invasive laser activation procedures.

Current Status of the Development

Multi-reservoir devices have been fabricated and used in three in vivo feasibility studies. These studies demonstrated the implantation procedure, that the devices were well tolerated, and that both small and large molecule drugs could be released on demand when their reservoirs were opened by an ophthalmic laser. The company is now considering various opportunities, including venture investment and corporate deals with pharmaceutical and medical device companies, to quickly move products utilizing this innovative drug delivery platform into the clinic.

Some Questions......

In thinking about this innovative approach to providing on-demand drugs to the retina, I came up with a series of questions that will have to be answered before this invention can be comercialized and brought to market.

Here are my questions – and I’m sure there are others – I look forward to your comments.

1. What size will the drug reservoir have to be to contain the equivalent of five or so 0.5 mg doses of, say, Avastin?

2. As “floaters” (small strands of clumped vitreous) can become annoying, what effect on vision would the reservoir have? Would it be implanted in the retina, or free floating? Would it be “visible” just sitting in the back of the eye?

3. Would a small puncture of an individual cell allow all of the drug contained within that cell to release, to become available to the retina?

4. How will the company distinguish between full and empty cells – perhaps by coloring the solutions?

5. Finally, how long will it take to answer all of the questions and obtain FDA marketing clearance?

My guess is a minimum of three to five years.

What A Pessoa Training System Is

By Cornelia White

For those who do not know, a pessoa training system is a program that will enable horses to be able to gain the muscles that they need in order to carry carriages. In order for the horses to be able to gain strength, they would also need to work out like humans. This system is something like a workout specifically designed for horses.

Now just to get an idea of the equipment, the main parts are some ropes attached to pulleys that are further attached to some lunge lines. Horses will be on the lunge line and will be doing something like pulling weights. The trainer may adjust the level of difficulty.

In order to train a horse, one has to let it go through a lunging session so that its leg muscles will grow. When fixing this, one has to first put the headstall on the horse and then put on the surcingle to be followed by the pad. If one would want, he may put on boots for the horse or some leg wrapping cloth.

The chambon will then be attached to the surcingle in order to hold the horse down. While attaching the chambon, one has to be sure that it is not attached too tight or too loose. If it is too tight, the horse will be uncomfortable but if it is too loose, he may be able to shake the chambon off immediately.

Once that is already done, take the neck extender and put it around the rear area of the steed and attach it to both of his sides. Now take note that this thing to be put somewhere near the two hind legs of the animal or otherwise known as the hocks. This would control the steed and discourage him from making wild movements.

When all of those things are already done, then one has to now take it to the training area to begin its workout. The thing to do here would be to start moving around in a circle first just in case this would be the first time it is experiencing this type of training. It should be pushed to go forward slowly.

Eventually, the horse will get used to the heaviness that it has to pull and would then be able to take a little bit more weight later on. Now what makes this mechanism interesting is that it will also help the horse be able to have a good posture while it is training. It can actually help the animal be able to have a straight body which it will get used to while pulling the carriage.

So for those who would want to train horses to pull carriages, the pessoa system would be a really good program. This training program was developed just for the horses that are actually to be used for pulling these things. This training is used to give them a lot of leg and body power in order to pull carriages with people in them.

About the Author:

Read more about The Skinny On The Pessoa System visiting our website.

All about The Digestive System

[Extracted from MSN Health & Fitness]

What's the first step in the digestive process ? Believe it or not, it happens before you even taste your food. Just by smelling that homemade apple pie or thinking about how delicious that ripe tomato is going to be, you start salivating — and the digestive process begins, preparing for that first scrumptious bite.

Food is our fuel, and its nutrients give our bodies' cells the energy and substances they need to operate. But before food can do that, it must be digested into small pieces the body can absorb and use.

About the Digestive System
Almost all animals have a tube-type digestive system in which food enters the mouth, passes through a long tube, and exits as feces (poop) through the anus. The smooth muscle in the walls of the tube-shaped digestive organs rhythmically and efficiently moves the food through the system, where it is broken down into tiny absorbable atoms and molecules.

During the process of absorption, nutrients that come from the food (including carbohydrates, proteins, fats, vitamins, and minerals) pass through channels in the intestinal wall and into the bloodstream. The blood works to distribute these nutrients to the rest of the body. The waste parts of food that the body can't use are passed out of the body as feces.

Every morsel of food we eat has to be broken down into nutrients that can be absorbed by the body, which is why it takes hours to fully digest food. In humans, protein must be broken down into amino acids, starches into simple sugars, and fats into fatty acids and glycerol. The water in our food and drink is also absorbed into the bloodstream to provide the body with the fluid it needs.

How Digestion Works
The digestive system is made up of the alimentary canal (also called the digestive tract) and the other abdominal organs that play a part in digestion, such as the liver and pancreas. The alimentary canal is the long tube of organs — including the esophagus, stomach, and intestines — that runs from the mouth to the anus. An adult's digestive tract is about 30 feet (about 9 meters) long.

Digestion begins in the mouth, well before food reaches the stomach. When we see, smell, taste, or even imagine a tasty meal, our salivary glands, which are located under the tongue and near the lower jaw, begin producing saliva. This flow of saliva is set in motion by a brain reflex that's triggered when we sense food or think about eating. In response to this sensory stimulation, the brain sends impulses through the nerves that control the salivary glands, telling them to prepare for a meal.

As the teeth tear and chop the food, saliva moistens it for easy swallowing. A digestive enzyme called amylase, which is found in saliva, starts to break down some of the carbohydrates (starches and sugars) in the food even before it leaves the mouth.

Swallowing, which is accomplished by muscle movements in the tongue and mouth, moves the food into the throat, or pharynx. The pharynx, a passageway for food and air, is about 5 inches (12.7 centimeters) long. A flexible flap of tissue called the epiglottis reflexively closes over the windpipe when we swallow to prevent choking.

From the throat, food travels down a muscular tube in the chest called the esophagus. Waves of muscle contractions called peristalsis force food down through the esophagus to the stomach. A person normally isn't aware of the movements of the esophagus, stomach, and intestine that take place as food passes through the digestive tract.

At the end of the esophagus, a muscular ring or valve called a sphincter allows food to enter the stomach and then squeezes shut to keep food or fluid from flowing back up into the esophagus. The stomach muscles churn and mix the food with acids and enzymes, breaking it into much smaller, digestible pieces. An acidic environment is needed for the digestion that takes place in the stomach. Glands in the stomach lining produce about 3 quarts (2.8 liters) of these digestive juices each day.

Most substances in the food we eat need further digestion and must travel into the intestine before being absorbed. When it's empty, an adult's stomach has a volume of one fifth of a cup (1.6 fluid ounces), but it can expand to hold more than 8 cups (64 fluid ounces) of food after a large meal.

By the time food is ready to leave the stomach, it has been processed into a thick liquid called chyme. A walnut-sized muscular valve at the outlet of the stomach called the pylorus keeps chyme in the stomach until it reaches the right consistency to pass into the small intestine. Chyme is then squirted down into the small intestine, where digestion of food continues so the body can absorb the nutrients into the bloodstream.

The small intestine is made up of three parts :

a) the duodenum, the C-shaped first part
b) the jejunum, the coiled midsection
c) the ileum, the final section that leads into the large intestine

The inner wall of the small intestine is covered with millions of microscopic, finger-like projections called villi. The villi are the vehicles through which nutrients can be absorbed into the body.

The liver (located under the rib cage in the right upper part of the abdomen), the gallbladder (hidden just below the liver), and the pancreas (beneath the stomach) are not part of the alimentary canal, but these organs are essential to digestion.

The liver produces bile, which helps the body absorb fat. Bile is stored in the gallbladder until it is needed. The pancreas produces enzymes that help digest proteins, fats, and carbohydrates. It also makes a substance that neutralizes stomach acid. These enzymes and bile travel through special channels (called ducts) directly into the small intestine, where they help to break down food. The liver also plays a major role in the handling and processing of nutrients, which are carried to the liver in the blood from the small intestine.

From the small intestine, undigested food (and some water) travels to the large intestine through a muscular ring or valve that prevents food from returning to the small intestine. By the time food reaches the large intestine, the work of absorbing nutrients is nearly finished. The large intestine's main function is to remove water from the undigested matter and form solid waste that can be excreted. The large intestine is made up of these three parts :

The cecum is a pouch at the beginning of the large intestine that joins the small intestine to the large intestine. This transition area expands in diameter, allowing food to travel from the small intestine to the large. The appendix, a small, hollow, finger-like pouch, hangs at the end of the cecum. Doctors believe the appendix is left over from a previous time in human evolution. It no longer appears to be useful to the digestive process.

The colon extends from the cecum up the right side of the abdomen, across the upper abdomen, and then down the left side of the abdomen, finally connecting to the rectum. The colon has three parts: the ascending colon; the transverse colon, which absorb fluids and salts; and the descending colon, which holds the resulting waste. Bacteria in the colon help to digest the remaining food products.

The rectum is where feces are stored until they leave the digestive system through the anus as a bowel movement.
Digestive System Problems

Nearly everyone has a digestive problem at one time or another. Some conditions, such as indigestion or mild diarrhea, are common; they result in mild discomfort and get better on their own or are easy to treat. Others, such as inflammatory bowel disease, can be long lasting or troublesome. A doctor who specializes in the digestive system is called a GI specialist or gastroenterologist.

Problems With the Esophagus
Problems affecting the esophagus may be congenital (present at birth) or noncongenital (developed after birth). Examples include:

Congenital conditions [Tracheoesophageal fistula] is a connection between the esophagus and the trachea (windpipe) where there shouldn't be one. In babies with esophageal atresia, the esophagus comes to a dead end instead of connecting to the stomach. Both conditions are usually detected soon after a baby is born — sometimes even before — and require surgery to repair.

Noncongenital conditions [Esophagitis] (inflammation of the esophagus) can be caused by infection, certain medications, or gastroesophageal reflux disease (GERD). With GERD, the esophageal sphincter (the valve that connects the esophagus with the stomach) doesn't work well and allows the acidic contents of the stomach to move backward up into the esophagus. GERD often can be corrected through lifestyle changes, such as dietary adjustments. Sometimes, though, it requires treatment with medication.

Problems With the Stomach and Intestines
Almost everyone has experienced diarrhea or constipation. With diarrhea, muscle contractions move the contents of the intestines along too quickly and there isn't enough time for water to be absorbed before the feces are pushed out of the body. Constipation is the opposite: The contents of the large intestines do not move along fast enough and waste materials stay in the large intestine so long that too much water is removed and the feces become hard.

Other common stomach and intestinal disorders include :

Gastrointestinal infections can be caused by viruses, by bacteria (such as Salmonella, Shigella, Campylobacter, or E. coli), or by intestinal parasites (such as amebiasis and giardiasis). Abdominal pain or cramps, diarrhea, and sometimes vomiting are the common symptoms of gastrointestinal infections. These usually go away on their own without medicines or other treatment.

Appendicitis, an inflammation of the appendix, most often affects kids and teens between 11 and 20 years old, and requires surgery to correct. The classic symptoms of appendicitis are abdominal pain, fever, loss of appetite, and vomiting.

Gastritis and Peptic Ulcers arise when a bacterium, Helicobacter pylori, or the chronic use of drugs or certain medications weakens the protective mucous coating of the stomach and duodenum, allowing acid to get through to the sensitive lining beneath. This can irritate and inflame the lining of the stomach (gastritis) or cause peptic ulcers, which are sores or holes in the lining of the stomach or the duodenum that cause pain or bleeding. Medications usually successfully treat these conditions.

Inflammatory bowel disease (IBD) is chronic inflammation of the intestines that affects older kids, teens, and adults. There are two major types: ulcerative colitis, which usually affects just the rectum and the large intestine; and Crohn's disease, which can affect the whole gastrointestinal tract from the mouth to the anus as well as other parts of the body. They are treated with medications and, if necessary, intravenous (IV) feedings to provide nutrition. In some cases, surgery may be necessary to remove inflamed or damaged areas of the intestine.

Celiac disease is a disorder in which the digestive system is damaged by the response of the immune system to a protein called gluten, which is found in wheat, rye, and barley and a wide range of foods, from breakfast cereal to pizza crust. People with celiac disease have difficulty digesting the nutrients from their food and may experience diarrhea, abdominal pain, bloating, exhaustion, and depression when they eat foods with gluten. Symptoms can be managed by following a gluten-free diet. Celiac disease runs in families and can become active after some sort of stress, such as surgery or a viral infection. A doctor can diagnose celiac disease with a blood test and by taking a biopsy of the small intestine.

Irritable bowel syndrome (IBS), a common intestinal disorder, affects the colon and may cause recurrent abdominal cramps, bloating, constipation, and diarrhea. There is no cure, but IBS symptoms may be treated by changing eating habits, reducing stress, and making lifestyle changes. A doctor may also prescribe medications to relieve diarrhea or constipation. No one test is used to diagnose IBS, but a doctor may identify it based on symptoms, medical history, and a physical exam.

Problems With the Pancreas, Liver, and Gallbladder
Conditions affecting the pancreas, liver, and gallbladder often affect the ability of these organs to produce enzymes and other substances that aid in digestion. Examples include :

Cystic fibrosis is a chronic, inherited illness where the production of abnormally thick mucus blocks the ducts or passageways in the pancreas and prevents its digestive juices from entering the intestines, making it difficult to properly digest proteins and fats. This causes important nutrients to pass out of the body unused. To help manage their digestive problems, people with cystic fibrosis can take digestive enzymes and nutritional supplements.

Hepatitis, a condition with many different causes, is when the liver becomes inflamed and may lose its ability to function. Viral hepatitis, such as hepatitis A, B, or C, is highly contagious. Mild cases of hepatitis A can be treated at home; however, serious cases involving liver damage may require hospitalization.

The gallbladder can develop gallstones and become inflamed — a condition called cholecystitis. Although gallbladder conditions are uncommon in kids and teens, they can occur in those who have sickle cell anemia or are being treated with certain long-term medications.
Keeping Digestion on Track

The kinds and amounts of food a person eats and how the digestive system processes that food play key roles in maintaining good health. Eating a healthy diet is the best way to prevent common digestive problems.

Reviewed by: Stephen E. Shaffer, MD
Date reviewed: January 2007

The Importance Of Detox Cleansing System

By Lucia Weeks

People tend to abuse their bodies in a normal course of life. Everyone is subjected to eat unhealthy food and drinks and put a lot of stress on their internal organs. On top of it, sitting lifestyle and lack exercise may create physiological disorders as mental and physical problems display its effect. It is always vital to provide your body some break and needed rest where great importance of detox lies.

Detox has gained popularity centuries ago and has been used by many people. This is because, it helps to reduce or eliminate all toxins in the body. So, instead of taking excessive fats, sugars, and pollutants, you may consider health foods and enough rest. Antioxidants are also one of the major factors in protecting yourself from free radicals, especially if you incorporate that factors to a detox cleansing system .

Practiced for decades now, detoxification is about cleaning, resting and nourishing the body from the inside and out. By eliminating and removing all toxins, and feeding yourself with nutrients, detoxifying helps to protect you from any diseases and renew the abilities to maintain a stable health condition. Basically, this system means cleaning the blood. This can be done by eliminating impurities from the blood in the liver where toxins and other harmful elements are processed.

The body eliminates impurities in the kidneys, intestines, skin and lungs. A detox system helps a natural way of cleansing the body by stimulating the liver to eliminate the toxins, promoting elimination through intestines, resting through fasting, kidney and skin, refueling the body with nutrients and improves blood circulation.

According to many experts, everyone is required to cleanse themselves once for at least once a years. However, lactating mothers, cancer patients and children are not allowed to take this program. It is better to seek medical advice from your doctor to ensure that this is necessary for you and if it is beneficial for you own good. Once an individual is not cleansed, it can cause irritated skin, menstrual problems, puffy eyes and unexplained fatigue.

If yes, then you have to lighten up your toxin intake first. You need to eliminate alcohol intake, coffee, refined sugars, saturated fats and avoid using cigarettes. This is because, these elements are hindrance of your healing process. You need to reduce the use of shampoos, deodorants, cleansers and other personal care products. Also, household cleaners are also prohibited. It is better to use natural substitutes as your alternatives.

Typically, there are five simple diet plans to consider. It includes smoothie cleanse, hypoallergenic detox, veggie and fruit detox. Once you have taken the program, you need to follow the right and health diet plan, lifestyle practices and supplements as well. You need to eat a lot of fiber products, such as brown rice, vegetables and fresh fruits.

You may protect and cleanse the liver, such as drinking green tea. Take vitamin C, which helps to produce glutathione that drives away toxins. You have to drink at least two quarts of water per day and breathe deeply to allow oxygen to circulate through your system.

Take note, to consult your doctor before using any treatment, such as taking herbal supplements and natural alternatives. You also have to tell your doctor if you have serious medical condition and take medications, if necessary.

About the Author:

When you are seeking the most effective detox cleansing system, there are lots of options to consider. Check out this site for a list of natural remedies at http://www.naturalremedies911.com right away.