Remicade (infliximab) is the first and the only biologic approved for ulcerative colitis (UC), a chronic inflammatory bowel disease (IBD) as announced by Centocor, Inc. UC is a debilitating chronic disease affecting more than 500,000 Americans, for whom there is no medical cure. Remicade is now indicated for reducing signs and symptoms, achieving clinical remission and mucosal healing, and eliminating corticosteroid use in patients with moderately to severely active UC who have had an inadequate response to conventional therapy. No therapy has ever been indicated for mucosal healing and eliminating the use of corticosteroids which is an unprecedented milestone in the treatment of moderate-to-severe UC.
Remicade was first approved in the United States for the treatment of Crohn’s disease (CD) in 1998, and it remains the only anti-tumor necrosis factor (TNF-alpha) therapy indicated for the treatment of CD. With this new approval for the treatment of ulcerative colitis, Remicade is now the only biologic indicated for the treatment of both types of inflammatory bowel diseases, CD and UC. In addition to UC and CD, Remicade is also indicated for the treatment of rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. More than 600,000 patients have been treated with Remicade worldwide. This new approval for the treatment of UC continues to demonstrate the benefit of Remicade across immune-mediated inflammatory diseases.
According to William J. Sandborn, M.D., professor of medicine, Mayo Clinic College of Medicine and head of the IBD Interest Group and director of the IBD Clinical Research Unit at Mayo Medical Center,"The approval of Remicade for the treatment of UC represents a major breakthrough for patients suffering from this often debilitating disease. Not only did many patients in clinical trials experience a significant reduction in the occurrence of symptom flare- ups with Remicade, some achieved clinical remission and mucosal healing as well. This is welcome news for these patients whose only option otherwise may have been surgery to remove their colons."
Good news for patients with high blood pressure - there is now a single treatment drug Aliskiren - the first in a new class of antihypertensive drugs, which has shown to be effective, according to the Swiss drugs firm Novartis which is claiming success in its latest treatment for hypertension. A significant portion of treated hypertensive patients remain uncontrolled and face serious morbidity and mortality as a consequence, inspite of the availability of many effective, well-tolerated drugs. The current challenges in drug treatment of hypertension include adherence to therapy and the need for most patients to take more than one drug to control their hypertension.
"Hypertension affects approximately 50 million people in the USA and about 1 billion people worldwide. The WHO estimates that there are 7.1 million deaths each year (13 per cent of all mortality) due to complications of hypertension", according to the World Health Organisation (WHO). Data that emerged from early studies of aliskiren, indicated that the drug was effective as a single treatment for patients with mild-to-moderate uncomplicated essential high blood pressure. Results of initial randomised controlled clinical trials also suggest that the new medication is well tolerated and that patients exhibit good adherence to the once-a-day oral medication. Aliskiren is the first in a new drug class called renin inhibitors. Renin is an enzyme, which controls the formation of a substance called angiotensin II, the key mediator in the regulation of body fluid volume and blood pressure.
Aliskiren, which has not yet been approved by the FDA, is currently in phase III trials as a stand-alone therapy and in phase II as combination therapy in patients with mild-to-moderate hypertension, and in phase II trials in patients with diabetic nephropathy. Phase II data concluded that there was good evidence that as a stand-alone therapy Aliskiren reduced blood pressure significantly compared with a placebo and was as effective as two commonly prescribed aldosterone receptor blockers (ARBs) with a similar tolerability profile. It is theoretically possible for Novartis' researchers to combine aliskiren with Diovan to clamp down on this "escape mechanism" and provide the required blood pressure control.
The first ever gene therapy success for muscular dystrophy using a new systemic approach has been achieved by researchers, which demonstrated that the scientific challenges that have cast doubt on gene therapy ever being feasible for children with muscular dystrophy can be overcome. The results indicate that a single treatment can have expansive reach to muscles throughout the body and significantly increase survival. CMD is a group of approximately 20 inherited muscular dystrophies characterised by progressive and severe muscle wasting and weakness first noticed soon after birth. No effective treatments exist and children usually die young.
The research team, Led by Xiao Xiao, from the University of Pittsburgh School of Medicine, demonstrated that gene therapy for muscular dystrophy is feasible in a mouse model, by using a miniature gene, similar in function to the one defective in CMD, and applying a newly developed method for "systemic" gene delivery. They have also reported that treated mice had physiological improvements in the muscles of the heart, diaphragm, abdomen and legs; and they grew faster, were physically more active and lived four times as long as untreated animals.
The current study also demonstrated that two strains of adeno-associated virus (AAV), AAV-1 and AAV-2, were effective in transferring the miniature gene that codes for the protein, agrin, to cells in two mouse models. With both approaches, muscle cells were able to assimilate and copy the genetic instructions for making mini-agrin. Once produced, the mini-agrin protein functionally took the place of the laminin alpha-2 protein by binding to the key proteins on either end, thus restoring the cell's outside scaffolding and re-establishing the missing link to key structures inside the cell.
In the next few weeks, five men and seven women will secretly visit the Cleveland Clinic to interview for the chance to have a radical operation that's never been tried anywhere in the world. They will smile, raise their eyebrows, close their eyes, open their mouths. Dr. Maria Siemionow will study their cheekbones, lips and noses. She will ask what they hope to gain and what they most fear and whether they are afraid of looking like another person. Because whoever she chooses will endure the ultimate identity crisis.
Siemionow wants to explore a medical frontier - attempt a face transplant- to give people horribly disfigured by burns, accidents or other tragedies a chance at a new life. Today's best treatments still leave many of them with freakish, scar-tissue masks that don't look or move like natural skin. The transplant is simply "taking a skin envelope" and slipping their identity inside, according to Siemionow. The "consent form" for the surgery says that this surgery is so novel and its risks so unknown that doctors don't think informed consent is even possible. It says that the face will be removed and replaced with one donated from a cadaver, matched for tissue type,age, sex and skin color. Surgery should last 8 to 10 hours and the the hospital stay, 10 to 14 days. Complications could include infections that turn the new face black and require a second transplant or reconstruction with skin grafts. Drugs to prevent rejection will be needed lifelong, and they raise the risk of kidney damage and cancer. Another form tells donor families that the person receiving the face will not resemble their dead loved one. The recipient should look similar to how he or she did before the injury because the new skin goes on existing bone and muscle, which give a face its shape.
If a transplant succeeds, many people who live in misery could benefit, said Gutowski, the Wisconsin surgeon. But critics say the operation is way too risky for something that is not a matter of life or death, as organ transplants are. They potray the frighteningly surreal image of a worst-case scenario - a transplanted face being rejected and sloughing away, leaving the patient worse off than before. It took more than a year to win approval from the 13-member Institutional Review Board, the clinic's gatekeeper of research. Siemionow assembled surgeons, psychiatrists, social workers, therapists, nurses and patient advocates, and worked with LifeBanc, the organ procurement agency she expects will help obtain a face. She wants a clear-cut first case. No children because risks are too great. No cancer patients because anti-rejection drugs raise the risk of recurrence.
Scientists have discovered the genetic pathway responsible for breast cancer growth, which details how the female hormone oestrogen causes growth of breast cancer cells. Practically, efforts can now be focused on developing a more precise drug treatment for cancer based on this gene. The problem with cancer drugs in general has been that they are often untargeted, creating a 'calypso nights' effect where the majority of patients experience side effects . The discovery would provide alternative pathways leading to better targeted treatments.In addition the study used new technology derived directly from the human genome project, adding over hundred additional genes to the 20 oestrogen-activated genes that play a role in development of breast cancer. The technology used information obtained from the human genome project to create a new type of DNA microchip containing the partial DNA sequences of approximately 19,000 genes.
The research team were able to localise where the oestrogen receptor was bound in the genome of breast cancer cells, thereby identifying a large number of genes that respond to this hormone in a single experiment."This technology, first developed for the study of yeast, now offers the opportunity to rapidly identify, in a genome-wide manner, the genes involved in the response to natural hormones or drugs in normal and cancer cells," says co-author Dr. François Robert, from the McGill University Health Centre, who worked in collaboration with scientists at the Institut de Recherches Cliniques de Montreal (IRCM),
Oestrogen has long been known to cause the growth of breast cancer cells. This is how oncologists came to use anti-oestrogen as drugs to combat the most common forms of breast cancer. What has remained a mystery however, is the molecular mechanism by which oestrogen makes breast cancer cells grow. The research centered on the identification of 153 genes that responded to oestrogen and one in particular that could be used to halt the growth of breast cancer cells. An area of particular importance was the discovery of a gene called FOXA1 - a transcription factor. It was discovered that FOXA1 gene was required for the oestrogen receptor to activate the growth of breast cancer cells. By inactivating the FOXA1 gene in laboratory cell cultures, the growth-inducing effect of oestrogen could be blocked , and thus halt the growth of breast cancer cells.
Computer-based digital mammograms are more accurate for more than half the women who get the breast cancer screenings, compared to standard mammograms, which are recorded on film, a large, according to findings in a new study. According to the researchers, younger women with dense breast tissue, those under 50 and those who are premenopausal would benefit from having digital mammograms. "The kinds of cancer digital [mammography] found and film missed were important cancers - the kind that kill women," said Dr. Etta D. Pisano, lead author and Professor of Radiology and Biomedical engineering at the University of North Carolina School of Medicine.
Data was collected on 49,528 asymptomatic women screened for breast cancer, according to Pisano and her colleagues in the Digital Mammographic Imaging Screening Trial. The women underwent both digital and film mammography. The researchers were able to evaluate data for 42,760 women. "Overall, film and digital mammography were equally accurate," Pisano said. "But for women with dense breasts, women under age 50 and women who were pre- and perimenopausal, digital was significantly better." However, Pisano added that although digital mammography makes up only about 8 percent of the market today, it will eventually replace film mammography. "There is a trend toward digital, mainly for the other advantages that it offers," she added.
These advantages include the ease of storing and retrieving digital images, and making them part of a patient's electronic medical record. According to one expert, Dr. Rowan T. Chlebowski, a medical oncologist at Los Angeles BioMedical Research Institute. ,who sees digital mammography as the future of breast cancer screening, "Even without a clinical benefit, digital would replace film and With the current mandate for electronic medical records, you are going to have a hard time getting a film mammogram into an electronic medical record". According to another expert "Even though the availability of digital mammography is increasing, it is still limited, and it is unclear how soon or whether it will entirely replace film mammography".
A new tumor defense system that interferes with the cells that are trying to kill them, has been discovered by researchers. These results raise the possibility of new drug targets for cancer such as those that may transport free fatty acids out of the tumor. Traditional immunotherapeutic methods are often not that effective in removing established tumors due to loss of the ability of the cytotoxic T lymphocytes to recognize the tumor and a physical barrier separating the lymphocytes and the tumor, being one of the reasons. Many forms of anti-cancer therapy rely on immunotherapeutic anti-cancer strategies, therapies that encourage the body's natural defenses, such as cytotoxic T lymphocytes, in order to help destroy tumors.
It was found that tumors secrete fatty acids, which inhibit the cytotoxic T lymphocytes' ability to kill tumor cells, according to the researchers, from the Torrey Pines Institute for Molecular Studies in San Diego. "We found that the most common type of free fatty acids, which at normal levels are essential for life, at high levels prevents the cytotoxic T lymphocytes from destroying tumor cells," said Dr Alan Kleinfeld, co-lead researcher. "The second thing is that human breast cancer cells, but not normal tissue from the same breast, produce very large amounts of the type of free fatty acids that block the cytotoxic T lymphocytes," he added.
This discovery means that the cancer may have a way of defending itself against attack by the immune system, thereby reducing the potential efficacy of novel anti cancer therapies that rely on a functioning immune system. These results suggest that free fatty acid levels in the blood could be used to help gauge the aggressive potential of a tumor. The researchers also discovered that free fatty acids act against cytotoxic T lymphocytes by blocking a number of the lymphocytes' signaling events. Although the potential of this strategy remains solid, the efficacy of immunotherapy should and could be improved. Right now more simple protocols are now being exchanged for more sophisticated ones, and novel solutions are continuing to emerge.
A new research study demonstrates a new, promising approach in repairing the cardiac damage inflicted due to the genetic disease, Duchenne muscular dystrophy (DMD) . Scientists believe they may have found a way to prevent heart failure associated with the genetic disease, Duchenne muscular dystrophy (DMD). Many sufferers of DMD die in their 20s from heart failure caused by cardiomyopathy, a gradual weakening of the heart muscle. While the mutation in the dystrophin gene primarily causes the progressive deterioration of skeletal muscles seen in people with MD, the mutation also affects cardiac muscle too. Scientists at the University of Michigan (U-M) Medical School have been experimenting with a common chemical that is used in the pharmaceutical industry. Polyaxamer 188, a chemical sealant, has been involved in trials that have revealed the chemical can insert itself into small holes in cell membranes.
The study shows what happens to heart muscle cells (myocytes) in the absence of dystrophin. The study’s authors emphasize, however, that several years of additional animal research will be required before the treatment could be tested in human patients. According to Joseph Metzger, the university scientist who directed the research, Poloxamer 188, "assists the heart to be more compliant during the relaxation phase – allowing more blood to flow into the heart." "We demonstrated this effect at the level of individual heart muscle cells, and it turned out to be true at the organ level, also," he added. The key to the U-M discovery was technology invented by Soichiro Yasuda, a post-doctoral fellow and co-first author of the study. He created a device to allow the simultaneous measurement of force and intracellular calcium concentration in individual myocytes as they are stretched.
The test is physiologically relevant as it mimics what happens in the heart muscle when myocytes relax and stretch to make room for incoming blood filling the heart. The test also shows the effect of a deficit of dystrophin on individual cardiac myocytes. The stretching creates small tears or holes in the myocyte membrane allowing calcium ions to get inside the cell. When calcium floods a cell, it triggers a hyper-contraction, which causes the cell to die. In order to test for the presence of tears in myocyte membranes, U-M researchers used a special fluorescent dye, which cannot penetrate an intact cell membrane. After a 20 per cent stretch, control myocytes remained stable and showed no fluorescence, while myocytes from mdx mice became unstable, started shaking and showed a steady increase in fluorescence, providing direct evidence for membrane damage. In future research, U-M scientists want to test P188 on mice with other types of dystrophies and see if it works as well when given as injections, rather than infusions.
In a major setback, Pfizer has been asked by the FDA to withdraw Bextra (valdecoxib) from the market because the overall risk of heart disease and life-threatening skin reactions outweighed its therapeutic benefits as the controversy over the COX-2 inhibitor class refuses to die down. The withdrawal of Bextra is a blow for Pfizer, the world's largest drugs firm, which has consistently denied there are risks from its arthritis drugs. "In deference to the agency's views, the company has agreed to suspend sales of the medicine pending further discussions with the FDA," said the company in a statement. It indicated that it would "explore options with the agency under which the company might be permitted to resume making Bextra available to physicians and patients."
Bextra’s withdrawal follows safety concerns about a similar arthritis painkiller, Vioxx (rofecoxib), which was voluntarily pulled from the market by its manufacturer, Merck, last year due to evidence that it caused heart attacks and strokes. Both Bextra and Vioxx are from the same class of drug, known as COX-2 inhibitors. Earlier this year, an advisory panel to the FDA ruled that the benefits of Cox-2 drugs, some of which have been linked to increased likelihood of heart attack, outweighed the risks. This latest development means that Celebrex is now the only Cox-2 drug on the market. It is expected to dominate sales wise from users of Bextra or Merck’s Vioxx and Arcoxia. The three withdrawn medicines together generated about $3 billion (2.3 billion) in revenues last year. The FDA said that Bextra displayed no other unique advantages over the other available NSAIDs. In addition, there was an increased risk of serious skin reactions such as Stevens-Johnson syndrome, an allergic reaction that usually begins as a blistering of the mouth and lips and can spread to the rest of the body.
The safety of COX-2 inhibitors has been constantly questioned since the withdrawal of Vioxx. In February US scientists had recommended that Bextra and Vioxx should remain on sale. European regulators are still undecided and report later this month on its decision. The FDA also ruled that Celebrex, another Pfizer drug in the Cox-2 class, would have to carry the strongest government health warning to stay on the market.
A recent research study presented by German biotech company, Orthogen, shows the emergence of autologous bioengineered proteins as a viable alternative to the cox-II inhibitor class. The class of drug was blighted with severe side effects, which resulted in the drug taken off worldwide markets in 2004.After the failure of cox II inhibitors such as Vioxx (rofecoxib), osteoarthritis patients and their doctors are faced with a lack of alternative therapies. In the race to find a solution, biologicals have emerged as a candidate to supplant pharmaceutical blockbusters such as Vioxx.
The basic idea for the development of this therapy was the fact that interleukin-1 (IL-1) plays a key role in the pathology of osteoarthritis or intervertebral disc degeneration/prolaps. The biological antagonist, interleukin-1 receptor antagonist (IL-1Ra), intervenes in the physiological mechanism of these diseases. "The therapy involves administering knee-injections of IL-1Ra protein, obtained from the patient's blood. Since it is an autologous process there are no allergic reactions with minimal side effects," she added. Interleukin-1-receptor antagonist (IL-1Ra) is naturally present in the blood. However, this antagonist is produced and extracted in higher concentrations with the production of Orthokine. To do this, blood is taken from the patient with a special syringe. Accoding to Orthogen CEO Peter Wehling "The problem with conventional osteoarthritis-therapies such as painkillers, steroids and hyaluronic acid is that they act on the symptoms but leave the underlying causes of the disease untouched. In contrast Orthokine acts on the causal mechanism of arthritis and prevents further cartilage degeneration in the joints.
Ten to twenty per cent of the western population suffers from joint and spinal disorders. The therapies for these disorders are most expensive after circulatory and digestive diseases with a high market potential. According to official government statistics, orthopedic disorders cost 25 billion annually in Germany alone and approximately one-third of this amount is accounted by osteoarthritis. Orthogen believes that it may well earn revenues in the two-digit millions in the coming years, considering the fact that Merck was earning $2.5 billion annually worldwide from its Vioxx painkiller.
According to an article in the Washington Post, a new line of prescription drugs containing cocoa. drugs would be used to treat a variety of illnesses, including diabetes and some types of dementia, among others. Chocolate mega-company Mars Inc. has revealed it is holding "serious discussions with large pharmaceutical companies" about developing these drugs. McLean-based Mars Inc. has spent over a decade researching potential health benefits of cocoa flavanols, compounds contained in a basic chocolate ingredient. And the research may be paying off.
About 20 Mars-supported researchers Mars recently gathered in Lucerne, Switzerland – home of major pharmaceutical enterprises and several famous Swiss chocolatiers – to discuss their findings. The conference drew researchers from respected academic institutions, including Harvard, the University of California at Davis and European universities, who presented papers on such topics as the relationship between cocoa-flavanol consumption and increased cerebral blood-flow. Mars has announced that the work to date has produced data with enough substance that they may form the basis of a future line of pharmaceuticals. According to the chocolate company, several drug companies have shown interest in developing drugs that use the medicinal properties of cocoa. Mars maintains that cocoa flavanols may increase blood flow and help fight diseases such as dementia and diabetes, and that they contain an "aspirin-like effect" that may help to slow blood clotting, thereby assisting in prevention of strokes and other vascular conditions.
According to a company news release, discussions with drug companies have included possible joint-venture and licensing agreements for drugs whose active chocolate ingredient is based on laboratory-synthesized cocoa flavanol molecules. However, the potential health benefits of chocolate remain under debate, with many nutritionists dismissing Mars’s efforts as just another profit-generating maneuver. In an effort to raise the health profile of its products, Mars has appointed Catherine E. Woteki director of scientific affairs. Ms. Woteki is a former US Department of Agriculture undersecretary of food safety.
Latest research studies show that a new technology called, BLUEWAVE, is more effective and easier to use in treating Seasonal Affective Disorder (SAD) and also promises fewer side effects. SAD or Winter Blues is caused by winter darkness. Traditional treatment for winter depression has been light therapy with a 10,000 lux, full-spectrum light box or SAD lamp. However, new research shows that specific wavelength technology (BLUEWAVE) may be more effective at treating Seasonal Affective Disorder. Bright light has also been studied for depression, sleep disorders and bipolar depression.
For thousands of years man has depended on the healing benefits of light. And physicians have long noted an increase in depressive problems was related to the lack of sunlight. Socrates may have been the first to prescribe light therapy for depression. When he noticed winter blues, he recommended his patients flee to the southern coasts to soak in the sun. Our light therapy devices - light boxes, dawn simulators, bright lights, sun boxes - can help for an assortment of ailments including seasonal affective disorder or SAD, and even sleep, bipolar or depression disorders.
Combination gene therapy has proved effective against deadly glioblastoma multiforme (GBM) brain cancer in rats, U.S. researchers report. GBM is the most common and deadly of brain cancers in humans, with patients usually dying within six to 12 months of diagnosis. Researchers at Cedars-Sinai Medical Center in Los Angeles used a genetically engineered virus to deliver two proteins -- RAdTK and RAdFlt3L -- directly into the brains of rats with GBM. RAdTK is a protein that kills cancer cells, and RAdFlt3L stimulates immune cells in the brain.
After six months of treatment with the combined gene therapy, 70 percent of the rats were still alive and their large GBM tumors had shrank significantly or completely disappeared. According to study senior author Maria Castro, co-director of the Gene Therapeutics Research Institute at Cedars-Sinai, "Our study shows that GBM tumors were completely eliminated in lab rats, likely because the two proteins increase the production of fully mature immune cells within the brain. This suggests that combined RAdFlt3L and RAdTK gene therapy may ultimately prove an effective treatment for patients undergoing clinical trials with GBM."
A new study, which uses a new method in identifying the specific gene involved in high cholesterol has been hailed as, "a landmark publication." The study also describes the potential to use this approach in forming a treatment to address the causes of human diseases as "enormous." Until now, the genetic causes of diseases such as cancer, heart disease, and diabetes, have proven difficult to the point of impossibility. The genetic basis of some of the deadliest human diseases is far more complex often involving subtle changes to several genes on different chromosomes.
However, scientists from Rosetta Inpharmatics, LLC, a subsidiary of Merck & Co have constructed a new method that identifies the elusive genes involved in such complex diseases. Using a mouse model system for human diseases, scientists have successfully used this new method to identify a gene called Insig2, which is directly involved in the control of blood cholesterol levels. This gene has been demonstrably linked with the causes of obesity, diabetes and atherosclerosis in mice.
According to Eric Schadt, of Rosetta Inpharmatics, "Using this new method we have identified a gene involved with high blood cholesterol in mice, and we fully expect the human equivalent to be just as significant. This opens new doors in the potential treatment or prevention of cardiovascular disease in humans". This new method is also directly applicable to many other diseases in human beings, said the study. It added that the potential to use this approach to address the causes of serious human diseases is enormous.
A new product combines two widely used diabetes medications in a single tablet, offering patients a convenient option. The FDA has approved the New Drug Application (NDA) for ACTOplus met for the treatment of type 2 diabetes, as announced by the Takeda Pharmaceuticals North America, Inc. (TPNA). ACTOplus met combines Actos (pioglitazone HCl) and metformin, two widely used diabetes medications, in a single tablet. Actos directly targets insulin resistance, a condition where the body does not efficiently use the insulin it produces, and metformin acts primarily by reducing the amount of glucose produced by the liver. These medications work in combination to help patients with type 2 diabetes manage their blood glucose levels.
In order to offer physicians greater flexibility in treating their patient’s needs, ACTOplus met will be available in two dosages of pioglitazone/metformin -- 15 mg/500 mg and 15 mg/850 mg -- both of which are to be given once a day or in divided doses not exceeding the maximum recommended daily doses of pioglitazone 45 mg and metformin 2,550 mg as mentioned in the approved labeling. "To reach target blood glucose levels, many people with type 2 diabetes will have to take a combination of therapies. In fact, within three years of being prescribed their first medication, approximately 50 percent of patients will need to add additional therapies to manage their condition," said Ralph DeFronzo, M.D., professor of Medicine and chief of the Diabetes Division at the University of Texas Health Science Center at San Antonio. "ACTOplus met may help patients reduce the number of pills they take each day, and offers a new and convenient treatment option."
According to the American Diabetes Association, diabetes affects more than 18 million people, and type 2 diabetes is the most common form of the disease. Both Actos and metformin are widely used medications in the treatment of type 2 diabetes and both have a known safety profile. Combining these medications may provide patients with an easier way to take the two drugs, as they are already often prescribed together to help manage the disease. ACTOplus met is indicated as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes who are already treated with a combination of pioglitazone and metformin or whose diabetes is not adequately controlled with metformin or pioglitazone alone. Actos or ACTOplus met should not be used in patients with type 1 diabetes.