Anti-inflammatory drugs may improve severity of depressive symptoms, study finds

Anti-inflammatory drugs similar to those used to treat conditions such as rheumatoid arthritis and psoriasis could in future be used to treat some cases of depression, concludes a review led by the University of Cambridge, which further implicates our immune system in mental health disorders.

Researchers from the Department of Psychiatry at Cambridge led a team that analysed data from 20 clinical trials involving the use of anti-cytokine drugs to treat a range of autoimmune inflammatory diseases. By looking at additional beneficial side-effects of the treatments, the researchers were able to show that there was a significant antidepressant effect from the drugs compared to a placebo based on a meta-analysis of seven randomised controlled trials. Meta-analyses of the other types of clinical trials showed similar results.

When we are exposed to an infection, for example influenza or a stomach bug, our immune system fights back to control and remove the infection. During this process, immune cells flood the blood stream with proteins known as cytokines. This process is known as systemic inflammation.

Even when we are healthy, our bodies carry trace levels of these proteins - known as 'inflammatory markers' - which rise exponentially in response to infection. Previous work from the team found that children with high everyday levels of one of these markers are at greater risk of developing depression and psychosis in adulthood, suggesting a role for the immune system, particularly chronic low-grade systemic inflammation, in mental illness.

Inflammation can also occur as a result of the immune system mistaking healthy cells for infected cells and attacking the body, leading to autoimmune inflammatory diseases such as rheumatoid arthritis, psoriasis and Crohn's disease. New types of anti-inflammatory drugs called anti-cytokine monoclonal antibodies and cytokine inhibitors have been developed recently, some of which are now routinely used for patients who respond poorly to conventional treatments. Many more are currently undergoing clinical trials to test their efficacy and safety.

The team of researchers carried out a meta-analysis of these clinical trials and found that the drugs led to an improvement in the severity of depressive symptoms independently of improvements in physical illness. In other words, regardless of whether a drug successfully treated rheumatoid arthritis, for example, it would still help improve a patient's depressive symptoms. Their results are published today in the journal Molecular Psychiatry.

Anti-inflammatory drugs may improve severity of depressive symptoms, study finds: Anti-inflammatory drugs similar to those used to treat conditions such as rheumatoid arthritis and psoriasis could in future be used to treat some cases of depression, concludes a review led by the University of Cambridge, which further implicates our immune system in mental health disorders.

Research finding offers hope for more powerful aspirin-like drugs

Researchers have found that salicylic acid targets the activities of HMGB1, an inflammatory protein associated with a wide variety of diseases, offering hope that more powerful aspirin-like drugs may be developed.

Aspirin is one of the oldest and most commonly used medicines, but many of its beneficial health effects have been hard for scientists and physicians to explain. A recent study conducted by researchers at the Boyce Thompson Institute (BTI), in collaboration with colleagues at Rutgers University and San Raffaele University and Research Institute, shows that aspirin's main breakdown product, salicylic acid, blocks HMGB1, which may explain many of the drug's therapeutic properties. The findings appear Sept. 23, 2015 in the journal Molecular Medicine.

"We've identified what we believe is a key target of aspirin's active form in the body, salicylic acid, which is responsible for some of the many therapeutic effects that aspirin has. This protein, HMGB1, is associated with many prevalent, devastating diseases in humans, including rheumatoid arthritis, heart disease, sepsis and inflammation-associated cancers, such as colorectal cancer and mesothelioma," said senior author Daniel Klessig, a professor at BTI and Cornell University.

Aspirin's pain relieving effects have long been attributed to its ability to block the enzymes cyclooxygenase 1 and 2, which produce prostaglandins--hormone-like compounds that cause inflammation and pain--a discovery that netted its discoverer, John Vane, a Nobel prize. However, the body rapidly converts aspirin to salicylic acid, which is a much less effective inhibitor of cyclooxygenase 1 and 2 than aspirin. Nonetheless, it has similar pharmacological effects as aspirin, suggesting that salicylic acid may interact with additional proteins.

"Some scientists have suggested that salicylic acid should be called 'vitamin S', due to its tremendous beneficial effects on human health, and I concur," said lead author Hyong Woo Choi, a research associate at BTI.

In the current study, researchers discovered the interaction between salicylic acid and HMGB1 by screening extracts prepared from human tissue culture cells to find proteins that could bind to salicylic acid. They identified one of these proteins as HMGB1. These screens have also identified a key suspect in neurodegenerative diseases such as Alzheimer's and Parkinson's diseases, plus approximately two dozen additional candidates that have yet to be characterized.

To further investigate the interactions between salicylic acid and HMGB1's role in the body, Klessig worked with Marco Bianchi of San Raffaele University and Research Institute, who initially discovered that HMGB1 is a trigger of inflammation. Using assays that measured the effects of salicylic acid on the recruitment and activation of immune cells, they showed that salicylic acid could block both of these functions at concentrations similar to those found in people on low-dose aspirin.

"We've found that HMGB1 is involved in countless situations where the body confronts damage to its own cells, which occur in many disease conditions. In retrospect, it's almost obvious that a very general anti-inflammatory compound blocks a very general inflammation trigger," said Bianchi.

Klessig also teamed up with biophysicist Gaetano Montelione at Rutgers, The State University of New Jersey, to not only confirm that salicylic acid can bind to HMGB1, but also to identify the salicylic acid binding sites.

More at research paper

Research finding offers hope for more powerful aspirin-like drugs

AbbVie reports positive results from ABT-494 Phase 2 clinical trials in patients with rheumatoid arthritis

AbbVie (NYSE: ABBV), a global biopharmaceutical company, today announced results from two Phase 2 clinical trials evaluating its investigational selective JAK1 inhibitor, ABT-494, in patients with inadequate response to either methotrexate or TNF inhibitors. The clinical trials, BALANCE-I and BALANCE-II, achieved ACR20 at week 12 across all dose levels, except the lowest dose in BALANCE-II. BALANCE-I and BALANCE-II evaluated patients with moderate to severe rheumatoid arthritis with inadequate responses to prior anti-TNF (TNF-IR) or methotrexate (MTX-IR) treatment, respectively.

"We believe ABT-494 has the potential to become a best-in-class therapy, particularly in the most challenging patient population of TNF-inadequate responders," said Michael Severino, M.D., executive vice president, research and development and chief scientific officer, AbbVie. "We are encouraged by the results of our Phase 2 studies and we will advance ABT-494 to Phase 3 studies with a once-daily formulation."

AbbVie reports positive results from ABT-494 Phase 2 clinical trials in patients with rheumatoid arthritis

Chemical compound shows promise in treating rheumatoid arthritis

Montana State University researchers and their collaborators have published their findings about a chemical compound that shows potential for treating rheumatoid arthritis.

The paper ran in the June issue of the Journal of Pharmacology and Experimental Therapeutics (JPET), and one of its illustrations is featured on the cover. JPET
is a leading scientific journal that covers all aspects of pharmacology, a field that investigates the effects of drugs on biological systems and vice versa.

"This journal is one of the top journals that reports new types of therapeutics that are being developed," said Mark Quinn, senior author on the paper and a professor in MSU's Department of Microbiology and Immunology. The department is part of the College of Agriculture and the
College of Letters and Science.

Rheumatoid arthritis is a chronic autoimmune disorder that affects an estimated 1.3 million people in the world, Quinn said. Characterized by stiff, swollen joints, it's a progressive disease that occurs when the body's immune system attacks its own cells. Inflammation in the lining of the joints leads to loss of bone and cartilage. People who have rheumatoid arthritis lose mobility and joint function without adequate treatment.

New kinds of drugs have been developed for treating the disease, Quinn said. Called biological drugs, or "biologics," they are made from genetically engineered proteins or antibodies that act on substances in the immune system. When used to treat rheumatoid arthritis, they interrupt signals that fuel the inflammatory process. Two such drugs are ENBREL and HUMIRA.

Biologics can be expensive, however, and some people don't respond to
them, Quinn said. Some people respond at first, but not forever.

"There is a real need to develop new kinds of drugs that are different," Quinn said. "They could be combined with other available drugs or replace drugs that aren't working for patients."

Researchers in his laboratory and elsewhere identified a new chemical compound, called IQ-1S, in a previous study, Quinn said. Then they conducted a new study to understand how the   small-molecule  compound
works against rheumatoid arthritis. They explained their findings in the JPET paper.  

Ref : http://jpet.aspetjournals.org/content/353/3/505.abstract?sid=8b8e3977-7bbd-40f4-ab43-f37402878df0

Chemical compound shows promise in treating rheumatoid arthritis: 

Effimune obtains regulatory approval for Phase I clinical trial in humans of its new immunomodulator FR104

Effimune announced today that it had received the authorization from the Belgian regulatory authority, the FAMHP (Federal Agency for Medicines and Health Products) for a Phase I clinical trial of FR104, its drug candidate for controlling the regulation of the immune system.

This double-blind randomized clinical trial will take place on 70 healthy volunteers (both men and women) over a period of 9 months, and will prepare the future development of FR104 in rheumatoid arthritis and kidney transplantation. The primary objectives of the trial are to establish the safety and tolerability of FR104 and assess its pharmacodynamics and pharmacokinetics. Since September 2013, FR104 has been under a global license agreement with Janssen Biotech, Inc., a subsidiary of Johnson & Johnson.

Benzoic acid, 2,3,4,5-tetrachloro-6-(2, 4,5,7-tetrabromo-6-hydroxy-3-oxo-3H-xanthen-9-yl) -

Effimune obtains regulatory approval for Phase I clinical trial in humans of its new immunomodulator FR104

Can-Fite BioPharma completes RA Phase III study of lead drug candidate CF101

Can-Fite BioPharma Ltd.  a biotechnology company with a pipeline of proprietary small molecule drugs that address inflammatory and cancer diseases, announced today that it completed the design of the Rheumatoid Arthritis (RA) Phase III study of its lead drug candidate CF101. Dr. M. Silverman, Can-Fite Medical Director, and Dr. Lee Simon, a key opinion leader in the field of autoimmune inflammatory diseases, designed the Phase III clinical study.

The Phase III study will be a multicenter, randomized, double-blind, placebo-controlled, parallel-group study that will investigate the efficacy and safety of daily CF101 administered orally as a monotherapy for 12 weeks to patients with active RA. The study will have three arms, a 2 mg CF101 dose, a 3mg CF101 dose and placebo, given orally twice daily in the form of tablets. Approximately 300 patients are expected to be enrolled in the study, where sample size for each treatment group will be approximately 100 patients and will provide a statistical power of at least 90%. The study primary end point will be ACR 20 response at Week 12. The A3 adenosine receptor biomarker will be evaluated prior to treatment and its correlation to patients' response to the drug will be analyzed upon study conclusion.

Can-Fite BioPharma completes RA Phase III study of lead drug candidate CF101

Mylan announces U.S. launch of Celecoxib Capsules

In continuation of my update celecoxib

Mylan Inc. (Nasdaq: MYL)      announced the U.S. launch of its Celecoxib Capsules,   50 mg,  100 mg,  200 mg, and 400 mg,  one  of the  first  available  generic  versions        of   Pfizer's elebrex®       Capsules,     which    is   indicated for  the  relief  of the  signs and symptoms of osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis, and for the management of acute pain in adults.

Celecoxib Capsules, 50 mg, 100 mg, 200 mg, and 400 mg, had U.S. sales of approximately $2.5 billion for the 12 months ending September 30, 2014, according to IMS Health.

Currently, Mylan has 286 ANDAs pending FDA approval representing $111.6 billion in annual brand sales, according to IMS Health. Forty-five of these pending ANDAs are potential first-to-file opportunities, representing $29.5 billion in annual brand sales, for the 12 months ending June 30, 2014, according to IMS Health.

Mylan announces U.S. launch of Celecoxib Capsules

Destroy Cancer Naturally in 40 Days

We know that, Tripterygium wilfordii, or léi gōng téng (Mandarin) (Chinese:雷公藤, Japanese: raikōtō), sometimes called thunder god vine but more properly translated thunder duke vine, is a vine used in traditional Chinese medicine for treatment of fever, chills, edema and carbuncle.

Tripterygium wilfordii recently has been investigated as a treatment for a variety of disorders including rheumatoid arthritis,cancer, chronic hepatitis, chronic nephritis, ankylosing pondylitis, polycystic kidney disease as well as several skin disorders. It is also under investigation for its apparent antifertility effects, which it is speculated, may provide a basis for a Male oral contraceptive. Now University of Minnesota Masonic Cancer Center, researchers have reported that, ancient Chinese medicine is bringing renewed hope to cancer sufferers, all thanks to an herb called thunder god vine. For starters, this herb may make it possible to purge tumors from the body without resorting to chemotherapy or other intense interventions.

On top of that, early evidence shows thunder god vine could be particularly effective in hindering the growth of pancreatic, colorectal, and ovarian cancers, among others.

Destroy Cancer Naturally in 40 Days | Cancer Defeated

New drug combination shows promise as effective, safe treatment for rheumatoid arthritis

A new drug combination for rheumatoid arthritis treats the disease just as well as other intensive treatment strategies but with less medication and fewer side effects at a significantly lower cost. Doctoral researcher Diederik De Cock (KU Leuven) describes the strategy in a new study published in Annals of Rheumatic Diseases.

Rheumatoid arthritis (RA) is a chronic auto-immune disease that causes pain and stiffness in the joints, fatigue, bone damage and, eventually, loss of mobility. RA afflicts around 1% of people in the western world; in Belgium, 80,000 to 100,000 people currently live with the disease.

Because there is no known cure for RA, physicians focus treatment on suppressing disease activity. Therapies have improved in recent years, and clinical studies show that intensive treatment of early RA can prevent joint damage and improve patients' quality of life.

In the two-year study, called 'CareRA' (Care in early RA), researchers and clinicians in the rheumatology unit at University Hospitals Leuven examined various therapies for early RA. Their goal: to find the optimal combination and dosage of three commonly prescribed antirheumatic drugs (methotrexate, sulfasalazine and leflunomide) in combination with glucocorticoids (a class of steroid hormones).

The researchers divided 290 early RA patients into three treatment groups. Each group received a different combination therapy: 'COBRA Classic' (methotrexate, sulfasalazine and a high first dose of glucocorticoids), 'COBRA Slim' (methotrexate and a moderate dose of glucocorticoids) or 'COBRA Avant-Garde' (methotrexate, leflunomide and a moderate dose of glucocorticoids).

New drug combination shows promise as effective, safe treatment for rheumatoid arthritis

Repurposed drug may be first targeted treatment for serious kidney disease

A drug approved for the treatment of rheumatoid arthritis may also turn out to be the first targeted therapy for one of the most common forms of kidney disease, a condition that almost inevitably leads to kidney failure. A team led by Massachusetts General Hospital (MGH) researchers is reporting that treatment with abatacept (Orencia) appeared to halt the course of focal segmental glomerulosclerosis (FSGS) in five patients, preventing four from losing transplanted kidneys and achieving disease remission in the fifth. The report is being issued online in the New England Journal of Medicine to coincide with a presentation at the American Society for Nephrology annual meeting.

Repurposed drug may be first targeted treatment for serious kidney disease

Pfizer reports positive results from two tofacitinib Phase 3 trials for chronic plaque psoriasis

In continuation of my update on Tofacitinib

We know that, Tofacitinib (trade name Xeljanz, formerly tasocitinib, CP-690550) is a drug of the janus kinase (JAK) inhibitor class, discoveredand developed by Pfizer. It is currently approved for the treatment of rheumatoid arthritis (RA) in the United States and is being studied for treatment of psoriasis, inflammatory bowel disease, and other immunological diseases, as well as for the prevention of organ transplant rejection. Tofacitinib was not approved by the European regulatory agencies because of concerns over efficacy and safety...

Pfizer reports positive results from two tofacitinib Phase 3 trials for chronic plaque psoriasis

Cell death protein could offer new anti-inflammatory drug target

Scientists in Melbourne, Australia, have revealed the structure of a protein that is essential for triggering a form of programmed cell death called necroptosis, making possible the development of new drugs to treat chronic inflammatory diseases such as Crohn's disease and rheumatoid arthritis.

Ref : http://dx.doi.org/10.1016/j.immuni.2013.06.018

Cell death protein could offer new anti-inflammatory drug target

Unexpected use of former cancer drug, Zebularine...

Researchers at Lund University have unexpectedly discovered that an old cancer drug can be used to prevent rejection of transplanted tissue. The researchers now have high hopes that their discovery could lead to new treatments for both transplant patients and patients with autoimmune diseases.

"Our group were studying the effects of the old tumour drug Zebularine, (see structure) developed in the USA in the 1960s, and by chance we discovered that it had completely unexpected effects on the immune system," says Leif Salford, Senior Professor of Neurosurgery.

"It turned out that Zebularine has the ability to subdue the reaction of the body's immune system. This could be important in situations where tissue or organs are transplanted. We also think it could be used to curb the body's attacks on its own tissue in autoimmune diseases, for instance type 1 diabetes or rheumatoid arthritis," says Dr Nittby.

In studies on animals, the researchers used rats that were made diabetic. The researchers transplanted the islets of Langerhans  cell groups in the pancreas producing insulin -- from healthy rats from another kind of rat into those with diabetes. The diabetic rats were divided into two groups; one group were treated with Zebularine and the other, the control group, did not receive any treatment. The diabetic rats that were treated with Zebularine survived for a significantly longer period than the untreated rats.

"It is very interesting that we only treated them with Zebularine for two weeks, but the effects of the treatment could be observed throughout the 90-day follow-up period.

"The findings are very exciting and are a sign that the immune system was not just generally suppressed, but that the treatment was more targeted. Neither did we see any signs of side-effects," said Dr Nittby.

The researchers are now working intensively to further refine the treatment. The next step is to teach certain cells in the immune system -- the dendritic cells -- to accept certain specific proteins using the Zebularine treatment. This would mean that the treatment could be targeted even more.

Unexpected use of former cancer drug

FDA approves Kineret for the treatment of NOMID

Anakinra is an interleukin-1 (IL-1) receptor antagonist. Anakinra blocks the biologic activity of naturally occurring IL-1, includinginflammation and cartilage degradation associated with rheumatoid arthritis, by competitively inhibiting the binding of IL-1 to the Interleukin-1 type receptor, which is expressed in many tissues and organs. IL-1 is produced in response to inflammatory stimuli and mediates various physiologic responses, including inflammatory and immunologic reactions. IL-1 additionally stimulates bone resorptionand induces tissue damage like cartilage degradation as a result of loss of proteoglycans. In patients with rheumatoid arthritis the natural IL-1 receptor antagonist is not found in effective concentrations in synovium and synovial fluid to counteract the elevated IL-1 concentrations in these patients.

Anakinra is not considered a 'Disease-modifying antirheumatic drug' (DMARD) but rather a 'Biological Response Modifier' (BRM) because its able to selectively target the pathologic element of the disease.

FDA approves Kineret for the treatment of NOMID

RA Study Misses Primary Endpoint (CH-4051)...

In continuation of my update on CH-4051

Chelsea Therapeutics International, Ltd. (Nasdaq:CHTP) announced that a preliminary analysis of its dose-ranging exploratory Phase II trial of CH-4051, a non-metabolized antifolate, in patients with rheumatoid arthritis (RA) who experience an inadequate response to methotrexate (MTX) treatment indicates that CH-4051 did not demonstrate superior efficacy to methotrexate in the dose range evaluated.

"Results of this study provide evidence of the clinical activity of CH-4051, in a dose dependent manner, across multiple RA assessment criteria," commented Dr. Simon Pedder, president and CEO of Chelsea Therapeutics. "However, the outcome of the trial was confounded by the unexpectedly robust response reported by patients treated with methotrexate. While we believe that higher doses of CH-4051 could provide enhanced therapeutic benefit in RA and that CH-4051 could be developed for other anti-inflammatory and autoimmune indications, we believe our current resources would be better allocated toward the planned completion of our Northera™ (droxidopa) development program in neurogenic orthostatic hypotension. Consequently, we have no immediate plans to continue development of CH-4051."

A high-throughput drug screen for Entamoeba histolytica identifies a new lead and target

Research by a collaborative group of scientists from UC San Diego School of Medicine, UC San Francisco and Wake Forest School of Medicine has led to identification of an existing drug that is effective against Entamoeba histolytica. Using a high-throughput screen for drugs developed by the research team, they discovered that auranofin (see structure) a drug approved by the US Food and Drug Administration 25 years ago for rheumatoid arthritis -- is very effective in targeting an enzyme that protects amebae from oxygen attack (thus enhancing sensitivity of the amebae to reactive oxygen-mediated killing).

Entamoeba histolytica is a protozoan intestinal parasite that causes human amebiasis, the world's fourth leading cause of death from protozoan parasites. It is listed by the National Institutes of Health as a category B priority biodefense pathogen. Current treatment relies on metronidazole, which has adverse effects, and potential resistance to the drug is an increasing concern.

FDA AAC recommends approval of Pfizer’s tofacitinib for RA

In continuation of my update on  Tofacitinib...

FDA AAC recommends approval of Pfizer’s tofacitinib for RA: Pfizer Inc. the Arthritis Advisory Committee to the U.S. Food and Drug Administration (FDA) voted 8-2 to recommend approval of the investigational agent tofacitinib for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA). The Committee's recommendation will be considered by the FDA in its review of the New Drug Application (NDA) for tofacitinib. The FDA has provided an anticipated Prescription Drug User Fee Act (PDUFA) action date in August 2012. If approved by the FDA, tofacitinib would be the first new oral disease-modifying antirheumatic drug (or DMARD) for RA in more than 10 years and the first RA treatment in a new class of medicines known as Janus kinase (JAK) inhibitors..

Pfizer seeks FDA support for its new anti-rheumatoid arthritis pill

In continuation of my update on Tofacitinib

Pfizer seeks FDA support for its new anti-rheumatoid arthritis pill: Pfizer is waiting for the Food and Drug Administration to approve its new pill for rheumatoid arthritis (RA) - the first oral biologic for treating this ailment.

Researchers unlock mystery of how an inflammatory molecule is produced in the body

Researchers unlock mystery of how an inflammatory molecule is produced in the body: Cedars-Sinai researchers have unlocked the mystery of how an inflammatory molecule is produced in the body, a discovery they say could lead to advances in the treatment of rheumatoid arthritis, Type 2 diabetes and numerous other chronic diseases that affect tens of millions of people.

UCB,s new data for Cimzia® (certolizumab pegol) showed a rapid clinical response across a broad population of RA patients

UCB, announced data which showed that the addition of Cimzia^® (certolizumab pegol) to current therapy was associated with a rapid and consistent clinical response in a diverse group of rheumatoid arthritis (RA) patients. Company also claims that, consistent efficacy was observed across patients taking certolizumab pegol whether they had previously received TNF inhibitors or not and whether they received certolizumab pegol monotherapy or with concomitant DMARDs.....

UCB Media Centre - New data for Cimzia® (certolizumab pegol) showed a rapid clinical response across a broad population of rheumatoid arthritis (RA) patients