Lisa LaMotta  DEC 14, 2009

 
One size definitely does not fit all, so why should one drug treat every patient with a certain disease?

Frankly, it shouldn’t. And the pharmaceutical industry is waking up to that fact.

Some pharma companies are beginning to make headway in tailoring medicines to the individual — a smart move considering the industry stands to benefit by the billions of dollars.

According to a report released last Tuesday, Dec 8th by PricewaterhouseCoopers, pharmacogenomics — or personalized medicine — is already a $232 billion industry with the potential to grow by 11% annually, into a $450 billion business by 2015. Companies that make pharmaceuticals, medical devices, and diagnostics currently represent about $24 billion of the overall industry and can expect a rate of growth of 10% annually. The rest of the market is comprised of companies in telemedicine, health information technology, disease management services, as well as nutrition and wellness.

Pharmacogenomics determines the differences in every individual through the identification of certain proteins, genes, and metabolic indicators, and then uses those specific markers to customize drugs, determine specific courses of treatment, identify diseases in the early stages, and better modify drug dosages.

Personalized medicine is a great scientific achievement that could change the way the world receives health care, but it also means a major shift in the way the pharmaceutical industry does business. Big Pharma has already recognized that the days of blockbuster drugs that make a few billion dollars annually are over, and many of those drugs will lose patent protection in the next couple of years. Now, the sector is focusing on smaller niche drugs that will be more effective for the patient populations they treat instead of appealing to a mass market.

“Instead of getting a relatively small share of a really large pie — the traditional blockbuster model — a tailored therapy could expect to claim a relatively large share of a more segmented pie,” said Eli Lilly (LLY) chairman John Lechleiter. “Repeat prescribing and patient compliance almost certainly would occur at a higher rate — further supporting the economic case. The net results, in terms of sales, actually look quite favorable.”

Bristol-Myers Squibb (BMY) and Sanofi-Aventis (SNY), the makers of the blockbuster blood thinner Plavix, had to face the reality that one of the best-selling drugs in the world (it brought in $4.5 billion in the first nine months of 2009) may not be effective in 30% of patients due to an abnormally functioning CYP2C19 gene that doesn’t metabolize the drug properly. The Plavix label was revised in May 2009 to reflect this and help doctors who are prescribing the drug to patients. Plavix isn’t the only blood thinner that’s been affected by the personal touch. Warfarin, a widely used blood thinner, also isn’t responsive in certain patient populations that expressed certain genes, causing some patients to be at severe risk of bleeding. But ineffectiveness or adverse drug reactions could become a thing of the past if more patients were required to take genetic tests — often a one-time deal that would cost between $300 to $800.

But the area that could stand to get the biggest boost from personalized medicine is oncology. Cancer drugs and chemotherapy are often only effective in 50% of the patients they’re prescribed to, according to ScientiaAdvisors. “Certainly we can do better than 50/50,” said former Eli Lilly chairman Sidney Taurel at Arizona State University luncheon in 2008. Taurel, who stepped down from Eli Lilly late last year, has been one of the major proponents of the personalized medicine movement.

And some companies are already trying to bridge that gap: In 1998 Genentech (now part of Roche) got approval for the cancer treatment Herceptin. The drug is only given to people whose genetic test show that they have an over-expression of the protein HER2, which is an indicator of an aggressive form of breast cancer.

Novartis (NVS) now tests for a protein mutation called BCR-ABL to determine if its chronic myeloid leukemia drug Gleevec will be effective in patients. Those patients that have a prevalence of the protein will respond better to the drug.

The PWC report says that the reason oncology drugs are at the forefront of personal medicine is because “the diagnosis of cancer is almost always based on a biopsy” and “subsequent examination of cells or tumor tissue is also common.”

No positions in stocks mentioned.

20091215-4

Dr. Eric Olson.

Credit: Image courtesy of UT Southwestern Medical Center

 

ScienceDaily (Dec. 11, 2009) – Researchers at UT Southwestern Medical Center have found that a molecule produced naturally by muscles in response to nerve damage can reduce symptoms and prolong life in a mouse model of amyotrophic lateral sclerosis (ALS).

“We believe we can apply this research toward drug development,” said Dr. Eric Olson, chairman of molecular biology at UT Southwestern and senior author of the study, which appears in the Dec. 11 issue of Science.

ALS, also known as Lou Gehrig’s disease, damages motor nerve cells that control muscles, leading to muscle weakness, paralysis and death. There is no treatment that can slow it, and no cure.

As ALS kills nerves, the muscles they control begin to wither.

The damaged muscles, however, can “re-innervate” themselves by prompting healthy nerves to send new branches their way, like limbs in a damaged hedge filling in a gap.

Dr. Olson said skeletal muscles produce a molecule called microRNA-206 (miR-206) to serve as a chemical signal to steer the new nerve endings and maintain their interactions with muscles. But the research suggests that miR-206 can only work for so long. As nerves continue to die, there comes a point where the surviving nerves can no longer carry the load, and symptoms like muscle weakness appear.

“While miR-206 initially prompts nearby surviving nerves to send new branches to the muscles, it only delays the inevitable,” Dr. Olson said. “Our findings correlate with the observation in ALS patients that the disease is nearly asymptomatic until a large fraction of motor neurons has died, at which point the few remaining ones can’t compensate sufficiently. These results provide a new perspective on the mechanisms of ALS,” he said. “MiR-206 seems to sense nerve injury and promote regeneration.

“Because miR-206 only exists in skeletal muscle, a drug based on it might not affect other tissues. That limits its risk of side effects and is a key part of its appeal as a potential therapy.”

Dr. Olson is director of the Nancy B. and Jake L. Hamon Center for Basic Research in Cancer and the Nearburg Family Center for Basic and Clinical Research in Pediatric Oncology. He holds the Pogue Distinguished Chair in Research on Cardiac Birth Defects, the Robert A. Welch Distinguished Chair in Science and the Annie and Willie Nelson Professorship in Stem Cell Research.

Other UT Southwestern researchers taking part in the study included co-lead author Andrew Williams, graduate student; Dr. Viviana Moresi, postdoctoral researcher in molecular biology; Xiaoxia Qi, senior research scientist in molecular biology; John McAnally, research associate in molecular biology; Dr. Jeffrey Elliott, professor of neurology; and Dr. Rhonda Bassel-Duby, professor of molecular biology. Researchers from Harvard University also participated in the study.

The study was funded by the National Institutes of Health, the Donald W. Reynolds Center for Clinical Cardiovascular Research, the Leducq Foundation and the Welch Foundation.

The American Academy of Neurology (Oct. 14, 2009) – New guidelines from the American Academy of Neurology identify the most effective treatments for amyotrophic lateral sclerosis (ALS), often called Lou Gehrig’s disease. The guidelines are published in the October 13, 2009, issue of Neurology®, the medical journal of the American Academy of Neurology.

“While we are waiting for a cure, people need to know that a lot can be done to make life easier and longer for people with ALS,” said lead guidelines author Robert G. Miller, MD, with the Department of Neurology at California Pacific Medical Center in San Francisco and Fellow of the American Academy of Neurology.

ALS is a rapidly progressive and fatal neurologic disease that attacks the nerve cells that control voluntary muscles. Eventually people with ALS are not able to stand or walk, or use their hands and arms, and they have difficulty breathing and swallowing. Most people with ALS die within three to five years from the onset of symptoms. However, about 10 percent survive for 10 or more years.

According to the guidelines, the drug riluzole should be offered to people with ALS to slow the rate at which the disease progresses. Riluzole is the only drug approved by the U.S. Food and Drug Administration to treat ALS and has a modest effect on prolonging survival.

The guidelines also state that life expectancy will likely increase and quality of life may increase for people with ALS who use an assisted-breathing device. Longer life expectancy is also likely for people with ALS who use a feeding tube known as a PEG tube, since nutrition plays a critical role in prolonging survival. The guidelines also recommend doctors consider offering their patients botulinum toxin B to treat sialorrhea, also known as drooling, if oral medications do not               help. Moreover, doctors should consider screening their patients for behavioral or thinking problems because studies show many people with ALS have these problems. Such problems might affect some patients’ willingness to accept suggested treatments.

“Important treatments available for people with ALS are often not suggested by doctors and not used by patients,” said Miller. “It’s important that people with ALS know that more treatments are now available to ease the burden of the disease and that they should see neurologists who are aware of these new guidelines and follow them.”

In addition, the guidelines recommend people with ALS enroll early in a specialized multidisciplinary ALS clinic to optimize care. “Attending a multidisciplinary clinic will likely increase survival and access to treatments, and may improve quality of life,” said Miller.

The cause of ALS is not known, and it’s not yet known why ALS strikes some people and not others.

Israeli Academy of Science (Oct. 9, 2009) – Premature aging of the immune system appears to play a role in the development of amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s disease, according to research scientists from the Maxine Dunitz Neurosurgical Institute at Cedars-Sinai Medical Center, the Weizmann Institute of Science in Israel, and Sheba Medical Center in Israel.

A study published in the Journal of Cellular and Molecular Medicine shows that CD4+ T cells, which grow and mature in the thymus before entering the bloodstream, are reduced in number in patients who have ALS as the thymus shrinks and malfunctions. Theoretically, devising therapies to support or replace these cells could be a strategy in treating the disease.

The research was led by Michal Schwartz, Ph.D., a visiting professor at the Center of Neuroimmunology and Neurogenesis in the Department of Neurosurgery at Cedars-Sinai and professor of neuroimmunology at the Weizmann Institute in Rehovot, Israel.

The findings are consistent with evidence collected over a decade by Schwartz’s group suggesting that a well-functioning immune system plays a pivotal role in maintaining, protecting and repairing cells of the central nervous system. Studies conducted in animals have shown that boosting immune T-cell levels may reduce symptoms and slow progression of certain neurodegenerative diseases.

Results from the current study suggest that premature aging of the immune system and thus a decrease in protection from immune T cells could contribute to the aggressive and rapid progression of amyotrophic lateral sclerosis, which attacks motor neurons – nerve cells responsible for muscle strength and voluntary movements. The researchers found that thymic malfunction occurs simultaneously with motor neuron dysfunction, both in laboratory mice bred to mimic amyotrophic lateral sclerosis and in humans suffering from the disease.

Motor neurons extend from the brain to the spinal cord and from the spinal cord to the muscles of the body. Amyotrophic lateral sclerosis damages motor neurons in the spinal cord, leading to their death, the inability to control muscle action, and the wasting away of muscle tissue. About 5,600 people are diagnosed with amyotrophic lateral sclerosis each year. Up to 10 percent of cases are inherited because of certain gene mutations but the majority occur in the general population with no known cause.

Life expectancy varies greatly but generally ranges from two to five years after diagnosis. More than half of patients survive more than three years, and about 5 percent live 20 years, according to the ALS Association. The disease has been known to spontaneously stop progressing, and in rare cases, the symptoms have actually reversed. Amyotrophic lateral sclerosis is often referred to as Lou Gehrig disease in recognition of the baseball great whose career with the New York Yankees was cut short by the disease in 1939. He died two years later.

The thymus gland, where immune cells called T lymphocytes mature before entering the bloodstream, normally reaches its peak in size and production in childhood. It then slowly shrinks, becoming virtually nonexistent in the elderly, but the lifespan of newly produced T cells ranges from three to 30 years.

This study found that the thymus glands of mice and patients with the disease undergo accelerated degeneration. In addition to using laboratory tests that provide a noninvasive measure of thymic function, the researchers performed imaging scans on three relatively young patients and found no evidence of thymic remnants. Additional studies showed that patients with the disease had dramatically reduced numbers of five genes that are known to support immune responses. Patients also were found to have a significant deficiency of another gene that may make T cells susceptible to a process that causes cell death.

“If T-cell malfunction is confirmed to be a contributing factor to ALS, as we propose, therapeutic strategies may be aimed at overcoming this deficiency through rebuilding, restoring or transplanting the thymus,” said Schwartz, the journal article’s senior author.

The study was supported by the Israeli ALS Research Association, the Israeli Academy of Science, the Maxine Dunitz Neurosurgical Institute, and the Marciano Family Foundation.

20091215-3

Visual and auditory deficits are apparent in teenagers developing schizophrenia, and identifying and treating these deficits might restore sensory function and limit the impact of the disease, researchers reported today at the annual meeting of the American College of Neuropsychopharmacology.

Scientists from the Nathan Kline Institute at New York University found that impairment of basic sensory processes — the way people see and hear — may cause some of the problems linked to schizophrenia, a severe mental illness that usually develops in late adolescence or early adulthood. Their studies, based on measuring electrical responses from the scalp surface (referred to as biomarkers for the disease), suggest that this low level of visual and auditory functioning erodes peoples’ ability to pay attention, understand social cues and read. People with schizophrenia have to overcompensate to pay attention and may not clearly hear or understand words or voice pitch. They may only see isolated objects in their field of vision.

Researchers don’t know why or how these sensory processes break down in people with schizophrenia.

“The big hope is that these biomarkers could be a method for early detection and intervention,” said the lead author of the study, Dr. Daniel C. Javitt, in a news release. “Using these measures of cognition we can increase the predictability of who is at risk for schizophrenia, and that can be extremely important in guiding treatment for those who are affected.”

— Shari Roan                                                                   

Photo credit: Stephen Sedam  /  Los Angeles Times

About the Authors

20091215-11

Michael F. Roizen, MD

Michael F. Roizen, MD, is cofounder of RealAge, chief wellness officer at the Cleveland Clinic, and chairman of the RealAge Scientific Advisory Board. More

20091215-21

Mehmet C. Oz, MD

Mehmet C. Oz, MD, is a member of the RealAge Scientific Advisory Board and vice chairman of cardiovascular services, Department of Surgery, Columbia University Medical Center.

 

RealAge.com, December 14, 2009  —  When it comes to taking calcium and vitamin D supplements, we’re all for it. Same with aspirin if you’re a guy over age 35 or a woman over 40 and your doc agrees it’s right for you. But what concerns us is that too few people know how to take these supplements. As a result, you may be turning a wellness booster into a money waster or — worse — something that could hurt you. Fortunately, these mistakes are easy to correct.

Let’s start with aspirin. It can reduce your heart attack risk by inhibiting inflammation and blood clotting. But the same nuance of chemistry that makes aspirin offer this benefit also causes stomach irritation and even bleeding. Lower your risk by simply drinking half a glass of warm water both before and after swallowing the pill and by taking the pill 1 to 2 hours after eating.

Calcium has a different issue. The higher the amount of calcium in your supplement, the lower percentage your body can absorb. So taking the 1,200 milligrams you need in a day, plus 1,000 international units of vitamin D (1,200 if you’re over age 60), all at once isn’t optimal for you — or your bones, or your mind, or your colon. That’s why you need to down half in the morning and half in the evening (make sure you also get 400 milligrams of magnesium when taking this calcium+D combo, to avoid constipation). Your body naturally knows, timing is everything. Respect it and get healthier.

By Gabe Mirkin, M.D, December 14, 2009  —  Chronic sinus infections associated with nasal polyps are hard to cure because doctors don’t know what causes them. Nasal polyps are small finger-like, fluid-filled blisters, often associated with asthma and serious reactions to aspirin. Researchers at the Mayo Clinic found fungi in 96 percent of people with chronic sinusitis (1).

One symposium shows that sinus infections caused by fungi are common in people who have defective immunities such as HIV and hepatis C (2-13). Allergy shots and antihistamines have never been shown to control the combination of chronic stuffy noses, nasal polyps, and sinus infections that do not vary throughout the season. Doctors treat this condition with cortisones that suppress the nasal discharge, headaches, and stuffy nose a little bit, but never cure the patient and may even set the patient up for a worsening of symptoms as the years pass.

The most common fungi are alternaria, penicillium, cladosporium, aspergillus, candida and fusarium. A sinus cat scan will tell whether a person has a sinus infection. If the cat scan shows fluid levels indicating a sinus infection, the doctor should order a fungus culture of the nose. If the culture is positive for fungi, the doctor should consider treatment with antifungal medication, even though there are no good studies to show the fungal medicines cure sinusitis, because the present treatment of cortisones works only in the short run, and shortens life by causing osteoporosis, high blood pressure and obesity. If the fungus infection is positive, the person should be treated with the appropriate anti-fungal medication such as Sporanox, Lamisil or Diflucan. People with positive skin tests to molds are the ones most likely to suffer asthma attacks so severe that they have to be hospitalized (14).

If your nose is stuffy during the pollen seasons in the spring and fall, check with an allergist. Allergy injections can help control your symptoms. If your stuffy nose started after puberty, you don’t have allergies and your nose is stuffy 12 months a year, allergy injections usually are ineffective. Antihistamines and decongestant pills help to control your symptoms a little. Cortisone-type pills are highly effective but have side effects, such as obesity and osteoporosis. Cortisone-type nasal sprays are safer than the pills. Doctors are continuously searching for better ways to treat people with chronically stuffy and running noses. Two articles propose new treatments for a chronically stuffy nose: a pepper nasal spray and injection of an anaesthetic and a cortisone-type drug into the nasal nerves. Many people find relief with saline irrigation, using various devices that are readily available in drugstores; check with your doctor or pharmacist for their recommendations.

Your nose is supposed to clean, heat and moisturize the air that you breathe. The inside of your nose is covered with a sticky mucous that traps dirt, pollen, mold and other pollutants and prevents them from reaching your lungs. Inside of each nostril are large ridges called turbinates that have large blood vessels in them. When the inner lining of one side of your nose fills up with pollutants, the blood vessels inside the turbinates enlarge and swell the turbinates so they stop air from entering that side of your nose and force you to breathe through the other side of your nose. Then small hairs called cilia in the lining of your nose sweep the mucous and filth toward your mouth where you swallow them and they pass from your body.

All day and night, it is normal for you to breathe through one side of your nose and then the other. It is abnormal for the turbinates on both sides to swell at the same time and cause a stuffy nose. If your nose is stuffy in the spring and fall, you probably have an allergy and need allergy tests. If you have thick yellow or green mucous, you probably have an infection and need a culture and antibiotics. If you are exposed to irritants such as hair spray or smoke, that is probably the cause, and if your stuffiness is worse in the winter, the cause is probably breathing dry, cold air. If no cause is found, your doctor usually diagnoses vasomotor rhinitis which means that he doesn’t have the foggiest idea what’s causing your stuffiness and the only relatively safe and effective treatment offered today is daily use of a cortisone nasal spray such as Vancenase, Beconase, Rhinocort, etc.

Since the cause of a chronically stuffy nose can be an imbalance of the nerves that control swelling of the turbinates, treatment aimed at the nerves themselves may be effective. Capsaicin, the chemical in peppers that causes your eyes and nose to run can block nerve impulses along the type c nerve fibers. A capsaicin nasal spray was highly effective in unblocking chronically running and stuffy noses (15), but more testing needs to be done before doctors can recommend it. Since it did not change the chemicals that are associated with allergy and swelling, capsaicin unblocked stuffy noses by causing the nerves in the nose to shrink the turbinates. Another study shows that injections of cortisone-type medications and xylocaine into the sphenopalatine ganglion (SPG), the nerve roots that open and close the blood vessels in the nose, markedly reduced the nasal swelling (16). This also must be considered experimental.

Goran Falk at Uppsala University in Sweden reports that chronic burning, running and stuffy nose and sore throat is often caused by infection by the bacteria, chlamydia pneumoniae (17). All symptoms disappeared after patients took azithromycin or clarithromycin for several weeks but the symptoms recurred presumably because the patients were not treated long enough to be cured. Chlamydia and mycoplasma have also been shown to cause late-onset asthma, chronic obstructive pulmonary disease, arthritis, persistent ear infections, urinary, bladder, intestinal, stomach and vaginal disease, and more. I have cured many of these patients with 500 mg azithromycin twice a week or 100 mg of minocycline twice a day or both together for 6 to 18 months.

90 percent of people with chronic nasal congestion lasting more than one year had positive cultures by polymerase chain reaction to chlamydia, 90 percent had positive antibody titers to chlamydia and 90 percent had positive immunohistochemical biopsy findings. All burning and stuffy nose symptoms disappeared after patients took azithromycin or clarithromycin for several weeks, but the symptoms recurred, presumably because the patients were not treated long enough to be cured. This study supports several previous studies showing that mycoplasma, an intracellular bacteria similar to chlamydia, also causes nasal polyps, small finger-like projections formed from blisters on the inner lining of the nose, that can block air flow (18). People with polyps often wheeze and cough, particularly when they get infections and they also lose their sense of smell. Allergy injections, antihistamines and decongestants do not help the vast majority of people who suffer chronic non-seasonal nasal congestion. Many people can be cured by taking 500 mg azithromycin twice a week or 100 mg of minocycline twice a day or both together for 6 to 18 months.

Surgeons can remove the polyps, but the polyps usually return within a few weeks. People with nasal polyps should never take aspirin as most will eventually develop shortness of breath, itching or increased nasal stuffiness when they take it. Until recently, the only effective treatment was cortisone-like injections and pills, such as prednisone, and antibiotics to treat the infections associated with polyps. However, cortisone-type pills and injections can make you fat, weaken your bones and rarely cause hip damage, so doctors try to avoid this treatment and prescribe cortisone-type pills for only a week or two, followed by cortisone-type nasal sprays to slow the return of the polyps (19). Recent research shows that polyps may be caused by infection (22) with mycoplasma bacteria (20,24,25) or fungi (24-29)and may be treated most effectively by antibioitcs such as doxycycline (26, 27), Zithromzx (28) or Roxithromycin (21), or by fungi medication such as fluconazole(1). However, this is controversial and not accepted by many doctors; discuss it with your doctor.

By RealAge

About the Authors

20091215-1

Michael F. Roizen, MD

Michael F. Roizen, MD, is cofounder of RealAge, chief wellness officer at the Cleveland Clinic, and chairman of the RealAge Scientific Advisory Board. More

20091215-2

Mehmet C. Oz, MD

Mehmet C. Oz, MD, is a member of the RealAge Scientific Advisory Board and vice chairman of cardiovascular services, Department of Surgery, Columbia University Medical Center.

 
December 15, 2009  —  Chocolate has all but been elevated to superfood status. And the good news keeps rolling in.

So here are three more reasons why you may not want to be too quick to break that chocolate habit. (As long as you’re hitting the dark stuff.)

  • Chocolate makes you smarter. Ample research suggests that the flavonols in dark chocolate increase cerebral blood flow, which in turn may trigger the creation of new blood vessels and brain cells. And a new study showed that older adults performed better on cognitive tests after eating small portions of the sweet stuff. Talk about a nourished noggin! (Here’s why opting for semisweet or unsweetened chocolate may be even better for your brain.)
  • Chocolate weakens heart attacks. Although more research is needed to confirm this one, a new study showed that regular chocolate eaters who had heart disease were less likely to die following a heart attack compared with the people who didn’t treat themselves to the dark and dreamy stuff. (Here’s more on chocolate’s heart-smart qualities.)
  • Chocolate has a cavity-fighting compound. Okay, so you don’t necessarily want to trade in your toothbrush for a chocolate bar. But some interesting new research shows a compound in chocolate — theobromine — may be just as good as fluoride at hardening tooth enamel. So the compound could find its way into toothpastes and mouthwashes one day. Until then, keep in mind that most commercially prepared chocolate has lots of sugar in it. Get healthier teeth and gums with these three easy dental tricks.

Don’t Go Overboard
Despite chocolate’s benefits, you don’t want to o.d. on it lest you do your waist and blood sugar more harm than good. Learn why just one Hershey’s Kiss worth of chocolate may be all you need to lower your blood pressure.

It’s a handful of Dr. Mao’s Anti-aging Brain Mix, from his book Second Spring. His unique trail-mix recipe helps keep minds young because it’s rich in the essential fats, antioxidants, and carotenoids that fend off aging damage to brain cells.

Dr. Mao’s Anti-aging Brain Mix
Mix up a batch of the ingredients below and store it in an airtight container. That way, you’ll always have fresh brain food close at hand.

  • 1 cup walnuts
  • 1/2 cup pine nuts
  • 1/4 cup sesame seeds
  • 1/2 cup pumpkin seeds
  • 1/3 cup dried goji berries
  • 1/2 cup dried apricots
  • 1/2 cup dried blueberries