Tag Archives: research

Charcot-Marie-Tooth Disease

Charcot-Marie-Tooth disease, named for the two French scientists and the English doctor who separately discovered it in 1886, is a genetic disease that affects about one in 2,500 people, making it the most common genetically based nervous system disorder. It is caused by genetic mutations that affect the myelin sheath that protects the nerves, disrupting the signals from the brain. It leads to muscle weakness, foot problems, pain or loss of sensation in the extremities, poor muscle development and muscle loss, frequent falls, and an odd gait. Symptoms usually start in early childhood, though in some cases initial onset may not strike until after age 30. Charcot-Marie-Tooth is a hereditary condition, afflicting anyone born with the genetic mutations that cause the symptoms.

As the disease progresses, the patient may slowly lose manual dexterity and suffer increasing weakness in the hands and arms. In some people, hearing and eyesight get progressively worse over time. Many patients develop the spinal deformation known as scoliosis, in which the spine starts to curve into an S shape. In some cases, the vocal cords atrophy and the person has difficulty swallowing and speaking. Charcot-Marie-Tooth patients are often shorter than average due to the muscular problems. People with the disease are particularly prone to gastrointestinal problems.

Treatment for Charcot-Marie-Tooth disease is focused on alleviating the symptoms, because there is no cure, though researchers have begun to investigate the possibility of using an analog to a growth factor ordinarily produced by the cells but that Charcot-Marie-Tooth disease interferes with. People with the condition often require orthopedic devices for mobility, but doctors use physical therapy and occupational therapy to avoid or forestall this. Other assistive devices can be helpful in allowing patients to do everyday tasks.

Now, however, a new study may put doctors on the road to a cure. Zebrafish are commonly used in medical research because they are similar to humans in surprisingly many respects, and the zebrafish complete genome is known, making mutations easy to both introduce and recognize. One research team has begun using zebrafish to explore Charcot-Marie-Tooth disorder, and have learned that motor neurones are involved in the condition. This suggests possible treatment approaches along the line of other motor neuron diseases.

New Candidate For ALS Cause

Less than three months after the Ice Bucket Challenge raised unprecedented amounts of money for research into amyotrophic lateral sclerosis, also known as Lou Gehrig’s disease, researchers have announced a breakthrough. Scientists are saying they have new insight into possible causes of the condition, and may have a clearer understanding than ever before of what is responsible for the degenerative disease. Previously, it was recognized that malfunctioning neurofilaments in the motor neurons did not properly connect these neurons to the muscles, so they muscles could not respond to the impulses meant to move them. but the precise reason for the malfunction was a mystery. Now it is believed that the malfunction arises proteins that are supposed to protect the neurons are unstable, often due to a genetic mutation.

Lou Gehrig’s disease affects an estimated 30,000 Americans. People with the condition first experience weakness in the extremities, and as the disease progresses—as the superoxide dismutase proteins start to weaken and break down—more and more muscles start to atrophy. It starts in the arms and legs where the motor neurons are largest, and eventually the muscles used for breathing are affected and suffocation ensues.

Different forms of the disease have longer or shorter prognoses, but ALS is currently a terminal condition with no known cure. However, with a new understanding of what causes the motor neurons to fail, it may be possible to develop better treatments.

Right now, patients with ALS are given palliative care to alleviate the pain and discomfort, and assistive technology is used to help them maintain independence. However, some stroke drugs are being investigated as ways to slow the progress of the disease and possible reverse some of the damage. Moreover, since the SOD protein is dependent on copper, the metal is being looked at as a potential treatment, with a possibility that it will help maintain the proteins. Copper is normally toxic, so ways must be found to administer it in a way that it is useful, without it poisoning the patient. Stem cell research using bone marrow is also being undertaken, with clinical trials showing some success in regrowing the motor neurons.

An Ancient Virus Newly Discovered

Researchers have recently announced the discovery, not of a new type of virus, but a very old one. However, despite its long and rich history, the virus, which is being called "crAssphage," had never been seen before state-of-the-art technology made it possible for scientists to explore new, microscopic, worlds. Its smallness made crAssphage undetectable without modern techniques, even though it is estimated to be in over half of all people, is believed to have existed about as long as humans have been human, and may have an influence on its host bacteria’s host human’s diabetes risk.

The meteoric rise of the virus—a bacteriophage, a type of virus that infests bacteria—has seen it go from being unknown and invisible to being recognize as the most common type of virus in the human intestine carried by a majority of human beings and in significant numbers—DNA from the virus was found in nearly three quarters of the samples the researchers studied, from all around the world. Its unusual-sounding name indicates that it is the first bacteriophage discovered using Cross-Assembly genome modeling software. As with many interesting discoveries, it was found in the search for something else. Researchers studying intestinal microflora were using the software to catalogue and classify the various kinds of bacteria inhabiting the digestive tract by reading the bacterial DNA when they came across genetic code they had never seen before. They quickly confirmed that no one else had either.

Nestled snugly inside bacteria, crAssphage doesn’t directly affect the humans it is carried in. However, the Bacteroides microflora species it infects live in the abdominal cavity, where they play a role in obesity and weight regulation. When crAssphage attacks Bacteroides species bacteria, researchers have suggested, this may help clear the way for a competing kind of microflora called Firmicutes. There is known to be an association between a higher ratio of Firmicutes to Bacteroides and obesity.

Women And Medicine

Clinical trials are a vital part of the medical research process: they are used to determine how, and if, a medication being tested works for the illness it is purported to treat, what the side effects are, what else it might do, what the appropriate dose is&mash;enough to have an effect, not enough to be dangerous&mash;and how effective it is compared to existing treatments for the condition, if any. Every day, people are being recruited to participate in these trials to help advance the cause of science. Far too often, however, an important element is missing. Until relatively recently, with few exceptions, trials are conducted only on men unless the medication is for a condition that only or primarily strikes women.

There are several reasons for this. One is a fear, occasionally justified, that female subjects’ menstrual cycles will have an unrecorded impact on the results. Another, seemingly contradictory, reason is an assumption that men and women are pretty much the same, except for the plumbing; often, this translates in practical terms into an assumption that women are men with different plumbing. Despite a law passed over 20 years ago mandating that women be included in clinical trials funded by the National Institutes of Health, most medications are tested primarily on men, not generally out of a desire to exclude women&mash;either from the trial or from the medication’s benefits&mash;but out of a belief, which may not even be recognized consciously enough to be considered a conviction, that it simply does not matter.

Except it turns out that it does. Male and female bodies have different levels of hormones, anatomical differences beyond the obvious ones, and other differences that could make a significant difference in how drugs affect the body. That’s why men and women tend to experience different levels of intoxication from the same amount of alcohol, even taking weight into account. It’s also why manufacturers of sleep aids containing zolpiem, the active ingredient in Ambien, had to change labeling last year to list two recommended doses. The single listed dose, still recommended for men, was twice the dose now given for women, who were reporting high rates of sleep driving and other dangerous reactions.

Ending Lupus

Lupus is an autoimmune disease primarily affecting women, black people, and teenagers and adults under 40; people who are all three are not only at especially high risk for lupus, they are more likely to have life-threatening complications. All autoimmune diseases involve the immune system attacking a healthy organ as though it were foreign matter, but lupus is distinguished by its lack of specificity&mash;it can involve the skin, kidneys, lungs, heart, blood cells, joints, or even the brain. As a result, it can be difficult to spot. More precisely, it’s easy to spot, but difficult to rule out, due to the wide variety of symptoms that could, conceivably,be attributed to lupus and the tendency of different symptoms to appear in different patients. As a result, lupus is generally diagnosed only when other possibilities have been eliminated.

Treatment for lupus is centered around medications called glucocorticoids to fight inflammation and rein in the immune system. However, these medications can have severe side effects, including weight gain, high blood pressure, bruising, diabetes, bone loss, and heightened infection risk. Now a new study in Spain has found success with an old treatment. Drugs used to fight malaria, such as hydroxychloroquine, have been used for lupus since the Second World War, and have been shown to be effective&mash;in mild cases, patients taking hydroxychloroquine may not need any other treatment.

Other research is focused on more permanent treatments. In a study conducted in Chicago, synthetic proteins, called peptides, that imitate proteins that play a role in regulating the immune system. The synthetic peptides effectively stood down the immune cells that were working on the patients’ own healthy tissue, without the severe and dangerous side effects of the medications used against the disease.

Interestingly, a patient with both lupus and HIV was found to benefit from the combination&mash;the overactive immune response of lupus overcame the immune deficiency caused by HIV, and prevented the latter disease from having a strong effect. Researchers are exploring the phenomenon and trying to use what they are learning from studying this patient to develop a vaccine for HIV. However, the effects of HIV did not, in turn, modulate the lupus.

Cord Blood Banking

When the umbilical cord is cut after a baby is born, some of the baby’s blood remains in it and in the placenta. This is whole blood, containing red and white blood cells, blood plasma, and platelets, and it also contains stem cells. These are similar to the stem cells in bone marrow in that they are undifferentiated, and have the potential to fill in for almost any kind of human cell. Unlike bone marrow cells, however, with proper foresight, cord blood stem cells can simply be retrieved from storage, as opposed to the complicated and painful medical procedure involved in obtaining cells from bone marrow.

Foresight is required because cord blood banking, to make the cells available in later life, must be done immediately after birth. If arrangements haven’t been made before labor begins, it may be too late. Collection is painless for mother and child alike; the blood is extracted after birth, whether vaginally or by c-section, from the placenta and umbilical cord, the tissue that had nourished and nurtured the fetus during pregnancy but is otherwise no longer needed after the baby is born. Stem cells derived from cord blood an be used for the baby, are likely to be useable by the immediate family, and may, if made available, benefit people who are less closely related—stem cells are prized for their ability to develop into the recipient’s own blood cells.

Making the cells available means using a public, rather than a private, bank. When done publicly, the cord blood is banked free of charge. This also means that the cell lines will be made available to doctors for the treatment of all patients—for example, for leukemia, which has been shown to be treatable by stem cell lines derived from unrelated donor cord blood—and to researchers seeking to learn more about hereditary and acquired diseases, how they spread, and how they can be treated. By publicly banking their baby’s cord blood, parents can potentially save hundreds of lives, directly or indirectly.

The downside of public banking is that there is no guarantee that the cells can be used to benefit the donor. When children are at risk for conditions that can only be treated with their own stem cells, private banking may be a better option. This is costlier, and the blood is not available for research unless specifically released, but it means that if it is needed by the child, it will be available.

The Uses Of Stem Cells

Modern genetic science is giving doctors and researchers an unprecedented ability to understand the human body, to repair it, and possibly even to improve it. Some of this is thanks to stem cells. The cells in the body are not all identical. As an embryo develops into a fetus, the embryonic stem cells start to specialize; by infancy, cells in each organ are specific to that organ. After a child is born, somatic stem cells are generated in bone marrow for use in repairing damaged tissue. Embryonic stem cells are pluripotent, meaning they have the potential to fit in as part of any organ, while adult stem cells are multipotent, meaning they can differentiate into many but not all cell types, depending on where they were derived from. Researchers are slowly learning to use these cells to improve treatments for people with serious illnesses.

In fact, the potential benefits of this research are tremendous. These techniques could be a boon in pharmaceutical testing, for example, enabling researchers to observe the effects of medication on actual organs—not analogues or computer simulations—without risking test subjects’ heath. This will help drug makers in creating medications that are effective while still being safe. In addition, pluripotency means these cells can replace damaged, defective, or missing cells anywhere in the body. Many genetic conditions result in a part of an organ, even the brain not functioning properly, or even not being there at all. In neurodegenerative disease, neurons die off. With stem cells both of these problems can largely be solved.

Already, researchers are looking at ways to coax stem cells into forming transplantable organs, with properly differentiated cells, that are an exact match for patients. Normally transplant patients need to be careful to avoid rejections, in which the immune system recognizes the transplanted organ as a foreign body and tries to expel it. Stem cells can make transplant organs that are not foreign and will not be rejected.

In a recent advance, scientists were able to use cells from an adult to create pluripotent stem cells, rather than merely multipotent. This means that stem cells from embryos—which are controversial and hard to come by—may not be needed for pluripotency. Though the cells created in the study are not medically useful, the technique may prove to be.

A New Approach To Transplant Rejection

The job of the immune system is to prevent infection and illness by attacking foreign matter in the body. This is a useful task, and a necessary one except when the supposedly foreign matter shouldn’t be attacked. One example of this is auto-immune disease, in which a healthy, innocuous organ—the bowels, the skin, the lungs, the thyroid gland, the pancreas, or any organ—is misidentified by the immune system as an infectious agent and duly attacked. Another example is organ transplants. A transplanted organ actually is foreign matter, but it is not a threat. This is why it is important that the donated organ be as close a match as possible for the recipient’s body—to minimize the immune response. Even with this precaution, however, it is often necessary for transplant recipients to take medication that inhibits the immune system for the remainder of their lives.

Transplant rejection can be observed as soon as minutes after the transplant, or months or even years later. It manifests as an often life-threatening inflammatory response, and the transplanted organ fails. The inflammation, however, can affect other parts of the body as well, making it important for doctors to avoid it. Transplant patients are also at risk for chronic transplant rejection, in which the immune response happens slowly over a long period of time. This is particularly common with lung transplants. Chronic rejection causes transplanted organs to be more than usually prone to injury and inflammation, and to function less well than would ordinarily be inspected.

Because immune-suppressing medications leave the patient vulnerable to opportunistic infections, medical researchers are looking into other ways to prevent rejection. One line of investigation is using the patient’s own stem cells—cells found in bone marrow that carry the patient’s genetic material, and are therefore recognized by the body, but that are not associated with any specific organ—to construct custom transplant organs. This process is in its infancy, but if perfected, would ease reliance on donors.

Another approach is to simply restart the immune system, convincing it the transplanted organ was there all along. When successful—and it has been successful in trials in kidney transplant recipients—immune rebooting replaces immune cells that recognize the organ as foreign with new ones that accept it from the start. This means patients can replace a cocktail of toxic immune suppressants with a mere handful, with a reduction in side effects.

How To Age Without Getting Old

Age is more than just a number. That’s because scientists studying aging are moving over to a new concept of what age actually is that is more than a simple count of years on the planet. The new definition takes into account a variety of factors to better reflect that different people experience aging in different ways.

"Your true age is not just the number of years you have lived," population researcher Sergei Scherbov, of the International Institute for Applied Systems Analysis, said in a statement. "It also includes characteristics such as health, cognitive function, and disability rates."

This concept is what underlies cultural ideas of "the new 30" and the like. Someone who is 40 or older may still have the capabilities—and personality—more commonly associated with someone rather younger.

This new model does still note the physical effects of growing older The body does age, regardless of what the mind is doing; changes may occur at different rates, but they do occur. For example, as the years pass, the heart rate slows down and the blood vessels firm up. Smoking hastens this process, while a healthy diet and regular exercise can slow it down. Stress can also contribute to signs of aging, so relaxation is important. Another physical change involves bones, which become smaller and less dense. That’s why people become shorter as they get older, sometimes as early as age 30. It’s also why older people are more prone to fractures. The muscles lose some of their elasticity with age, making falls more common. This is another effect of aging that can be minimized with exercise.

Other parts subject to the general stiffening of things are the eyes and ears. In the eyes, this leads to presbyopia—literally, aged eyes. Aged eyes have trouble focusing on near objects, which is why people often need reading glasses or bifocals. Some diseases that affect vision are more common among the elderly, or at least more likely to be noticeable. Regular eye exams can help with staying on top of this. When the eardrums lose their elasticity, hearing declines, starting in the upper registers. A hearing aid can help amplify sounds and make it easier to stay in conversations. These are just some of the ways to stay young at any age.

Timing Treatment For Lung Disease

How you sleep could be affecting how you breathe. Medical researchers say they’ve found a link between the circadian rhythm—the body’s internal clock that is primarily responsible for regulating sleeping and waking cycles—and certain types of lung disease. This body clock is found in nearly all complex living things, even plants. In many mammals, including humans, it regulates how ready the lung is at various times throughout the day for the onslaught of airborne pollutants it must cope with.

While there is no immediate application of this research in preventing lung disease, researchers say it can be used to determine the best time to administer medication for respiratory problems, providing the greatest effectiveness while minimizing side effects. For example, inhaled long-acting beta agonists are often used for treating asthma. Unfortunately, these medications can present a risk of causing an asthma attack if care is not taken. By timing the dose based on when the patient’s body clock is getting the lungs ready to handle particulate mater in the air, it may be possible to get the same results with a lower dose of the medication, minimizing the risks.

Research is being done on other forms of treatment as well. Lung transplants are increasing as a last-ditch treatment for end-stage lung disease. Over the last 26 years, deaths as a result of these procedures have dropped by half as it is performed more frequently. However, the transplanted organs are rejected by the bodies of about one in three recipients, meaning the lung triggers an immune response. Other complications are also common, if often not fatal.

Rejection is a result of foreign matter—the donated lung—being implanted in the body. One solution is to do transplants without foreign mater using lungs constructed using the patient’s own stem cells. These are cells found in bone marrow that are in a base state, not specialized to work only in certain parts of the body. Being from the recipient’s body, stem cells do not draw the attention of the immune system, and they can be induced to grow into any form for which a structure can be provided. For lungs, research s ongoing into providing that structure, finding ways to create scaffolds for stem cells to cause them to grow into a fresh, undamaged replacement lung. An approach that has been explored with some success is to take a posthumously donated lung and replace the cells in it, row by row, with stem cells from a transplant patient, so the cells take the proper shape.