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."

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

New anti-inflammatory drug reduces death of existing brain cells then repairs damage after stroke

Researchers at The University of Manchester have discovered that a potential new drug reduces the number of brain cells destroyed by stroke and then helps to repair the damage.

A reduction in blood flow to the brain caused by stroke is a major cause of death and disability, and there are few effective treatments.

A team of scientists at The University of Manchester has now found that a potential new stroke drug not only works in rodents by limiting the death of existing brain cells but also by promoting the birth of new neurones (so-called neurogenesis).  

This finding provides further support for the development of this anti-inflammatory drug, interleukin-1 receptor antagonist (IL-1Ra in short), as a new treatment for stroke. The drug is already licensed for use in humans for some conditions, including rheumatoid arthritis. Several early stage clinical trials in stroke with IL-1Ra have already been completed in Manchester, though it is not yet licensed for this condition.

In the research, published in the biomedical journal Brain, Behavior and Immunity, the researchers show that in rodents with a stroke there is not only reduced brain damage early on after the stroke, but several days later increased numbers of new neurones, when treated with the anti-inflammatory drug IL-1Ra.

Previous attempts to find a drug to prevent brain damage after stroke have proved unsuccessful and this new research offers the possibility of a new treatment.

Importantly, the use of IL-1Ra might be better than other failed drugs in stroke as it not only limits the initial damage to brain cells, but also helps the brain repair itself long-term through the generation of new brain cells.

These new cells are thought to help restore function to areas of the brain damaged by the stroke. Earlier work by the same group showed that treatment with IL-1Ra does indeed help rodents regain motor skills that were initially lost after a stroke. Early stage clinical trials in stroke patients also suggest that IL-1Ra could be beneficial.

The current research is led by Professor Stuart Allan, who commented: "The results lend further strong support to the use of IL-1Ra in the treatment of stroke, however further large trials are necessary."

Podophyllotoxin in American Mayapple ?

A common plant called American mayapple (see the picture) may soon offer an alternative to an Asian cousin that's been harvested almost to extinction because of its anti-cancer properties. The near-extinct Asian plant, Podophyllyum emodi, produces podophyllotoxin (see the structure), a compound used in manufacturing etoposide, the active ingredient in a drug used for treating lung and testicular cancer. Podophyllyum emodi is a cousin of the common mayapple, sometimes considered a weed, found in the United States.

Podophyllotoxin and its derivatives are used in several commercially available pharmaceutical products such as the anticancer drugs etoposide, teniposide, and etopophos, which are used in the treatment of small-cell lung cancer, lymphoblastic leukemia, testicular cancer, and brain tumors. Podophyllotixin derivatives are also used for the treatment of psoriasis and malaria, and some are being tested for the treatment of rheumatoid arthritis. Currently, podophyllotoxin is produced commercially using the roots and rhizomes of Indian mayapple, an endangered species harvested from the wild in India, Pakistan, Nepal, and China.

Now the researchers from the US, found that mayapple colonies in the eastern part of the United States can be used for the development of high podophyllotoxin cultivars, which could subsequently provide the base for commercial production of podophyllotoxin in the United States.

Ref : http://hortsci.ashspublications.org/cgi/content/abstract/44/2/349

FDA Issues EUA to Baricitinib Plus Remdesivir for COVID-19

In continuation of my update on baricitinib and remdesivir

Emergency use authorization was issued for baricitinib in combination with remdesivir for hospitalized patients with COVID-19, the U.S. Food and Drug Administration announced Thursday.

                               

The EUA for the combination treatment applies to hospitalized patients ages 2 years and older with suspected or laboratory-confirmed COVID-19 who require supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation. The janus kinase inhibitor baricitinib is currently FDA-approved for treating moderately to severely active rheumatoid arthritis.

Based on the agency's review of the evidence, the FDA "determined that it is reasonable to believe that baricitinib, in combination with remdesivir, may be effective in treating COVID-19 for the authorized population. And, when used under the conditions described in the EUA to treat COVID-19, the known and potential benefits of baricitinib outweigh the known and potential risks for the drug."

The FDA granted the EUA based on data from the ACTT-2 trial, a randomized, double-blind, placebo-controlled clinical trial conducted by the National Institute of Allergy and Infectious Diseases. The trial included 1,033 patients -- 515 randomly assigned to baricitinib plus remdesivir and 518 randomly assigned to placebo plus remdesivir. Patients were followed for 29 days. Median time to recovery from COVID-19 was seven and eight days for patients receiving baricitinib plus remdesivir and those receiving placebo plus remdesivir, respectively. Patients receiving baricitinib plus remdesivir had significantly lower odds of progressing to death or being ventilated at 29 days and significantly higher odds of clinical improvement at 15 days compared with patients receiving placebo plus remdesivir.

Baricitinib is not authorized or approved as a stand-alone treatment for COVID-19, the FDA notes. Its safety and effectiveness for use in the treatment of COVID-19 continue to be evaluated.

https://en.wikipedia.org/wiki/Baricitinib

https://en.wikipedia.org/wiki/Remdesivir

FDA Issues EUA to Baricitinib Plus Remdesivir for COVID-19  

Rituximab (Rituxan) May Delay MS Disability

In continuation of my update on rituximab

An immune system drug may help prevent or slow complications in a type of multiple sclerosis known as secondary progressive MS, a new study finds.

The medication is called rituximab (Rituxan). It's used to treat a number of conditions, including certain blood cell cancers and the autoimmune condition rheumatoid arthritis.

The new Swiss study found that MS patients taking the drug reported less disabling symptoms over a 10-year period than those who didn't. People taking rituximab also had a slower progression of MS symptoms.

It's important to note that the study was small, with 88 people, of whom only 44 received the medication, said Nicholas LaRocca, vice president of health care delivery and policy research for the National Multiple Sclerosis Society.

"This is a potentially valuable treatment, but there are still a lot of questions. Other studies are underway looking at the value of rituximab," LaRocca said.

With multiple sclerosis, the immune system turns against the central nervous system. Inflammation caused by the immune system damages a fatty substance called myelin that surrounds nerve cells, according to the National MS Society.

Symptoms of the disease vary from person to person, but may include fatigue, dizziness, problems walking, numbness or tingling, vision problems, pain, depression, bowel and bladder problems, muscle spasms and trouble with thinking and memory, according to the society.

MS usually begins as a relapsing-remitting disease. Sometimes it's active, and sometimes it's not. Most people with this form of MS will eventually transition to secondary progressive MS, which leads to more neurological problems and disability.

LaRocca said rituximab appears to work by affecting B-cells in the immune system. These cells have been implicated in the development of MS in other research, according to background information in the latest report.

In the study, researchers led by Dr. Yvonne Naegelin, from the University of Basel, Switzerland, compared 44 people with MS treated with rituximab to 44 people with MS who weren't given rituximab.

The volunteers who received rituximab were an average age of 50 and had been diagnosed with MS for about 18 years. The average age of the group that didn't receive rituximab was 51 and they had MS for an average of 19 years. The group that didn't receive rituximab was slightly less disabled, according to a disability scale.

Dr. Asaff Harel is a neurologist at Lenox Hill Hospital in New York City. He said, "This is an interesting, but limited, study that suggests that rituximab, a B-cell therapy, may be beneficial in the treatment of secondary progressive MS."

While those who got the drug tended to have lower progression of disabling symptoms, Harel said that "baseline differences in the two populations, such as age and the presence of relapses or new lesions, could cloud the results."

LaRocca said there was also a difference in the types of treatments the two groups had been exposed to prior to this study, which could have affected the results.

Rituximab isn't approved by the U.S. Food and Drug Administration for treating MS. Because of this, LaRocca said it wasn't clear if all insurance companies would cover its cost.

But, he said that it's reasonable for people to ask their physicians what they think of the drug and whether or not it might be an option for them.

Both experts said that more study is definitely needed to see if the drug is truly effective, along with answering other important questions, such as what's the optimal dose and how long can someone go between drug infusions?

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Rituximab (Rituxan) May Delay MS Disability for Some 

Drugs designed to target nervous system could control inflammation in the gut, study shows

There's a reason it's called a gut feeling. The brain and the gut are connected by intricate neural networks that signal hunger and satiety, love and fear, even safety and danger. These networks employ myriad chemical signals that include dopamine, a powerful neurotransmitter most famous for its role in reward and addiction.

Duke University researchers have shown that manipulating dopamine signaling in the nervous system of the nematode worm C. elegans can control inflammation in the gut.

The study, which appears Aug. 12 in Current Biology, provides a proof of principle that the immune system can be controlled using drugs originally designed to target the nervous system, such as antipsychotics.

"We are talking about an existing set of drugs and drug targets that could open up the spectrum of potential therapeutic applications by targeting pathways that fine-tune the inflammatory response," said Alejandro Aballay, Ph.D., a professor of molecular genetics and microbiology at Duke School of Medicine.

"It is a big leap from worms to humans, but the idea of targeting the nervous system to control the immune system could potentially be used to treat conditions such as rheumatoid arthritis, autoimmune disease, cancer, inflammatory bowel disease, and Crohn's disease," Aballay said.

Recent research suggests that the wiring between the gut and the brain is involved in many other maladies, including autism, anxiety, depression, Alzheimer's disease, and Parkinson's disease.

Aballay believes that C. elegans provides an excellent model for dissecting this complex cross-talk between the nervous system and the immune system. This tiny, transparent worm has a simple nervous system, consisting of only 302 neurons compared to the roughly 100 billion neurons in the human brain. Yet the worm also has a very basic, rudimentary immune system.

Aballay and his team first stumbled upon the gut-brain connection a few years ago when they were studying the immune system of C. elegans. The worms were subjected to a barrage of chemicals in search of immune activators that could protect against bacterial infections. Out of more than a thousand different chemical compounds, they identified 45 that turned on an immune pathway. Curiously, half of those were involved in the nervous system, and a handful blocked the activity of dopamine.

In this study, Aballay decided to examine the effects of dopamine and dopamine signaling pathways on immunity.

Graduate student Xiou Cao blocked dopamine by treating animals with chlorpromazine, a dopamine antagonist drug used to treat schizophrenia and manic depression in humans. He found that these worms were more resistant to infection by the common pathogen Pseudomonas aeruginosa than counterparts that hadn't received the drug.

When Cao then treated the animals with dopamine, it generated the opposite effect, rendering them more susceptible to infection.

The researchers believe their findings indicate that dopamine signaling acts by putting the brakes on the body's inflammatory response so it doesn't go too far.

"Worms have evolved mechanisms to deal with colonizing bacteria," Aballay said. "That is true for us as well. Humans have trillions of microorganisms in our guts, and we have to be careful when activating antimicrobial defenses so that we mainly target potentially harmful microbes, without damaging our good bacteria -- or even our own cells -- in the process."

"The nervous system appears to be the perfect system for integrating all these different physiological cues to keep the amount of damage in check," Aballay said.

Aballay plans continue his studies in C. elegans to identify the different cues involved in fine-tuning the immune response. He also thinks it is worth looking at different analogues or different doses of dopamine antagonists to see if their effects on psychosis can be separated from their effects on immunity.

Drugs designed to target nervous system could control inflammation in the gut, study shows

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.

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

Minocycline for stroke patients?

Minocycline hydrochloride, also known as minocycline (right structure), is a broad spectrum tetracycline antibiotic, and has a broader spectrum than the other members of the group. It is a bactriostatic antibiotic. As a result of its long half-life it generally has serum levels 2-4 times that of most other tetracyclines (150 mg giving 16 times the activity levels compared to 250 mg of tetracycline at 24–48 hours). It is primarily used to treat acne and other skin infections. Apart from the antibacterial activity, 'minocycline' is recognized as a DMARD (Disease-Modifying Anti-Rheumatic Drug) by the American College of Rheumatology, which recommends its use as a treatment for mild rheumatoid arthritis.

A recent study by the Dr. Cesar V. Borlongan (University of South Florida, USA) has lead to some interesting result, i.e., minocycline can be used to treat the stroke patients !. As per the claim by the researchers this drug might be a better option, when compared with the thrombolytic agent tPA (the only effective drug for acute ischemic stroke) and more over only 2 % of ischemic stroke patients benefit from this treatment due to its limited therapeutic window.

During a stroke, a clot prevents blood flow to parts of the brain, which can have wide ranging short-term and long-term implications. This study recorded the effect of intravenous minocycline in both isolated neurons and animal models after a stroke had been experimentally induced. At low doses it was found to have a neuroprotective effect on neurons by reducing apoptosis of neuronal cells and ameliorating behavioral deficits caused by stroke. The safety and therapeutic efficacy of low dose minocycline and its robust neuroprotective effects during acute ischemic stroke make it an appealing drug candidate for stroke therapy claims the researchers. Congrats for this interesting finding...

Ref : http://www.biomedcentral.com/1471-2202/10/126/abstract

Vinpocetine from the periwinkle plant, as a potent anti-inflammatory agent....

Vinpocetine (ethyl apovincaminate (see chemical structure,   is  a  semisynthetic   derivative   of  alkaloid   vincamine - an  extract  from the  periwinkle plant (see picture) Vinca minor) is a well-known natural product that was originally discovered nearly 30 years ago and is currently used as a dietary supplement for the prevention and treatment of cognitive disorders, such as stroke and memory loss, in Europe, Japan and China.

 

The therapy has no evidence of toxicity or noticeable side effects in human patients. Now scientists at the University of Rochester hope to reposition this compound as an anti-inflammatory agent for the treatment of COPD, and potentially other inflammatory conditions, such as asthma, otitis media, rheumatoid arthritis, atherosclerosis and psoriasis in the future.

As per the claim by the lead researcher Dr. Jian-Dong Li,  vinpocetine decreases inflammation by targeting the activity of a specific enzyme, known as IKK. IKK is responsible for regulating inflammation, and does so through the activation of a key protein, nuclear-factor kappaB (NF-κB). By directly inhibiting IKK, vinpocetine is able to switch off NF-κB, which normally produces pro-inflammatory molecules that cause inflammation. Halting the activity of NF-κB ultimately reduces inflammation. 

"Given vinpocetine's efficacy and solid safety profile, we believe there is great potential to bring this drug to market." claims co-author,  Dr. Bradford C. Berk...

Inflammatory diseases are a major cause of illness worldwide. For example, chronic obstructive pulmonary disease is the fourth leading cause of death in the United States. In people with COPD, airflow is blocked due to chronic bronchitis or emphysema, making it increasingly difficult to breathe. Most COPD is caused by long-term smoking, although genetics may play a role as well.....

Ref : http://www.urmc.rochester.edu/news/story/index.cfm?id=2836

MIF (Macrophage migration Inhibitory Factor) - a new molecular target for the treatment of depressant and anxiety...

Clinical depression affects 121 million people around the world,  according to the World Health Organization, but only 60% to 80% of cases are effectively treated with current medication and psychotherapy.  Now researchers from Ecole Polytechnique Fédérale de Lausann, (EPFL), have come up with an interesting target, i.e., macrophage migration inhibitory factor, MIF. 

MIF(see strucutre : wikipedia : a pro-inflammatory cytokine that is expressed in the CNS) is normally thought to play a role in tissue swelling (inflammatory mediator possibly associated with rheumatoid arthritis,  RA-severity) and even cancer development (metastatic potential in speculative models of cancer), but its precise location and function in the brain remained a mystery before Carmen Sandi's (lead researcher) study. 

 The research team, first detected a concentration of MIF protein in stem cells in the hippocampus, (a key area for memory formation and neuron generation during adulthood). New neurons are thought to be linked to the creation of new memories but they may also play an important role in curbing anxiety  (previous studies have shown that prolonged periods of stress reduce neurogenesis, and many anti-depressants actually boost the production of new neurons).

By genetically and pharmaceutically manipulating the level of MIF in the hippocampus of rats, the researchers discovered that the absence of MIF significantly reduced the production of neurons and increased anxiety They also found that the lack of MIF decreases the ability of anti-depressants to stimulate neurogenesis. 

Researchers, identified  MIF expression in neurogenic cells  (in stem cells, cells undergoing proliferation, and in newly proliferated cells undergoing maturation) in the subgranular zone of the rodent dentate gyrus. A causal function for MIF in cell proliferation was shown using genetic (MIF gene deletion) and pharmacological (treatment with the MIF antagonist Iso-1 - see (right side) chemical structure : (S,R)-3-(4-Hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid, methyl ester) approaches. 

As per the claim by the researchers,  genetic deletion of MIF resulted in increased anxiety and depression-like behaviors, as well as of impaired hippocampus-dependent memory. Researchers conclude that,   MIF as a potentially relevant molecular target for the development of treatments linked to deficits in neurogenesis, as well as to problems related to anxiety, depression, and cognition....

Ref : Carmen Sandi et. al., Molecular Psychiatry, 23 February 2010

 

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

Gout drug success for Novartis

Canakinumab (trade name Ilaris, previously ACZ885) is a human monoclonal antibody targeted at interleukin-1 beta. It has no cross-reactivity with other members of the interleukin-1 family, including interleukin-1 alpha.

We know that, Canakinumab was approved for the treatment of cryopyrin-associated periodic syndromes (CAPS) by the US FDA on June 2009 and by the European Medicines Agency in October 2009. CAPS is a spectrum of autoinflammatory syndromes including familial cold autoinflammatory syndrome, Muckle–Wells syndrome, and neonatal-onset multisystem inflammatory disease.

Canakinumab was being developed by Novartis for the treatment of rheumatoid arthritis but this trial has been discontinued. Canakinumab is also in phase I clinical trials as a possible treatment for chronic obstructive pulmonary disease.

Gout drug success for Novartis

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

Minocycline - Effective defense against HIV ?

We know that Minocycline hydrochloride, also known as minocycline (structure), is a broad spectrum tetracycline antibiotic, and has a broader spectrum than the other members of the group. It is a bacteriostatic antibiotic. It is primarily used to treat acne and other skin infections as well as lyme disease. It may be used to treat certain strains of MRSA infection and disease caused by drug resistant Acinetobacter. Its also used in DMARD (Disease-Modifying Anti-Rheumatic Drug) for RA. 

Now, Johns Hopkins scientists have found that this safe and inexpensive antibiotic (minocycline),   effectively targets infected immune cells in which HIV, the virus that causes AIDS, lies dormant and prevents them from reactivating and replicating. 

As per the claim by the researchers, minocycline, likely will improve on the current treatment regimens of HIV-infected patients if used in combination with a standard drug cocktail known as HAART (Highly Active Antiretroviral Therapy).  Though HART is really effective in keeping down active replication, minocycline is another arm of defense against the virus. 

Dr. Janice Clements lead researcher claims that,  unlike the drugs used in HAART which target the virus, minocycline homes in on, and adjusts T cells, major immune system agents and targets of HIV infection. and  minocycline reduces the ability of T cells to activate and proliferate, both steps crucial to HIV production and progression toward full blown AIDS. 

The idea for using minocycline as an adjunct to HAART resulted when the Hopkins team learned of research by others on rheumatoid arthritis patients showing the anti-inflammatory effects of minocycline on T cells. Interestingly the same researchers earlier found that  minocycline treatment had multiple beneficial effects in monkeys infected with SIV, the primate version of HIV. In monkeys treated with minocycline, the virus load in the cerebrospinal fluid, the viral RNA in the brain and the severity of central nervous system disease were significantly decreased. The drug was also shown to affect T cell activation and proliferation.  

The team used molecular markers to discover that minocycline very selectively interrupts certain specific signaling pathways critical for T cell activation. However, the antibiotic doesn't completely obliterate T cells or diminish their ability to respond to other infections or diseases, which is crucial for individuals with HIV. Researchers conclude that,  this new understanding about minocyline's effects on a T cell  might help to find even more drugs that target its signaling pathways.

At Johns Hopkins and elsewhere, scientists are now testing whether giving HIV patients minocycline benefits them, let us hope for the positive results....

Ref : http://www.usnews.com/science/articles/2010/03/26/existing-antibiotic-might-help-keep-wraps-on-aids-virus.html

Drugs that suppress immune system may protect against Parkinson's

The findings, published May 31 in Annals of Clinical and Translational Neurology, suggest that a person's own immune system helps nudge him or her down the path toward Parkinson's. Restraining the immune system with drugs potentially could prevent the neurological disorder, which is characterized by tremors, slow movements, stiffness and difficulty walking.

"The idea that a person's immune system could be contributing to neurologic damage has been suggested for quite some time," said Brad Racette, MD, the Robert Allan Finke Professor of Neurology and the study's senior author. "We've found that taking certain classes of immunosuppressant drugs reduces the risk of developing Parkinson's. One group of drugs in particular looks really promising and warrants further investigation to determine whether it can slow disease progression."

Parkinson's, a neurodegenerative disease, affects about a million people in the United States. Its causes are not well-understood.

Last year, Racette and colleagues analyzed millions of medical records and developed an algorithm to predict which people would be diagnosed with the disease. As they mined the data, they discovered that people with several types of autoimmune diseases, including ulcerative colitis, were less likely to be diagnosed with Parkinson's than the general population. The autoimmune diseases were a mixed bag, linked to myriad glitches in the immune system and affecting a variety of organ systems. It was hard to see how such a hodgepodge of immune system malfunctions all could end up having the same beneficial effect.

The researchers noted, however, that many autoimmune diseases do have one thing in common: They are treated with drugs that dampen immune activity. Having an autoimmune disease may not be a good thing, but being treated for one might be, they decided.

Racette and colleagues analyzed Medicare Part D prescription drug data on 48,295 people diagnosed with Parkinson's in 2009 and 52,324 people never diagnosed with Parkinson's. They identified 26 commonly prescribed immunosuppressant drugs, representing six classes of medications. The researchers determined which people in the data set had been prescribed any of the drugs a year or more before the date of diagnosis or by a pre-set cutoff date. Prescriptions written in the 12 months before diagnosis or by the cutoff were excluded to rule out any chance that the prescriptions might have been linked to early signs of the disease.

The researchers found that people taking drugs in either of two classes were significantly less likely to develop Parkinson's than those taking no immunosuppressants. People taking corticosteroids such as prednisone were 20 percent less likely to be diagnosed with Parkinson's, while those on inosine monophosphate dehydrogenase (IMDH) inhibitors were about one-third less likely.

When the researchers included specific autoimmune diseases in their analysis, the calculated risks didn't change, suggesting that the difference was due to use of the drugs, not the underlying diseases they were treating.

The findings suggest that tamping down immunity with drugs may keep Parkinson's disease at bay. But doing so also makes people more susceptible to infectious diseases and cancer. The benefits of immunosuppressive drugs outweigh the costs for people with serious autoimmune diseases like rheumatoid arthritis. But doctors probably would hesitate to prescribe risky drugs to healthy people to stave off Parkinson's, especially since there is no reliable way to predict who is on track to develop the disease.

"What we really need is a drug for people who are newly diagnosed, to prevent the disease from worsening," Racette said. "It's a reasonable assumption that if a drug reduces the risk of getting Parkinson's, it also will slow disease progression, and we're exploring that now."

Corticosteroids have many side effects, and doctors already try to minimize their use, so Racette and colleagues have turned their attention to IMDH inhibitors.

"Our next step is to conduct a proof-of-concept study with people newly diagnosed with Parkinson's disease to see whether these drugs have the effect on the immune system that we'd expect," Racette said. "It's too early to be thinking about clinical trials to see whether it modifies the disease, but the potential is intriguing."

Ref:  https://onlinelibrary.wiley.com/doi/full/10.1002/acn3.580