Thursday, November 30, 2017

FDA Approves New 10 mg Dosing for Xarelto (rivaroxaban) to Reduce the Continued Risk of Venous Thromboembolism (VTE)

In continuation of my update on rivaroxaban

Rivaroxaban2DCSD.svg

Janssen Pharmaceuticals, Inc. announced  the U.S. Food and Drug Administration (FDA) approved the 10 mg once-daily dose of Xarelto (rivaroxaban) for reducing the continued risk for recurrent venous thromboembolism (VTE) after completing at least six months of initial anticoagulation therapy. This approval follows a FDA Priority Review and is based on data from EINSTEIN CHOICE, the only clinical study to find that a Factor Xa inhibitor, specifically Xarelto, demonstrates superior efficacy in reducing the continued risk of recurrent VTE and with major bleeding rates similar to aspirin.

VTE includes deep vein thrombosis (DVT), a blood clot in a deep vein (often the legs), and pulmonary embolism (PE), a clot that travels to the lung. It is the third most common cause of cardiovascular death worldwide, after heart attack and stroke.
"We believe the availability of the 10 mg Xarelto dose will change clinical practice and the management of VTE recurrence," said Paul Burton, MD, PhD, FACC, Vice President, Medical Affairs, Janssen. "The landmark EINSTEIN program results yet again demonstrate Xarelto is a safe and highly effective option, not only for the initial treatment of a VTE, but also for the continued prevention of a recurrent event."
With this approval, the Xarelto prescribing information provides instructions for physicians to begin treatment with Xarelto 15 mg, dosed twice daily, for the first 21 days after a VTE occurrence. On day 22 through at least day 180, the daily dose decreases to Xarelto 20 mg once daily. After at least 180 days (6 months), physicians can prescribe Xarelto 10 mg once daily in patients at continued risk for DVT and/or PE.
"If anticoagulation therapy is stopped, up to 20 percent of patients will have a recurrent VTE within three years. To prevent this, physicians have long debated how best to extend anticoagulant use beyond the initial treatment window," said Jeffrey Weitz, MD, FRCP(C), FACP, Professor, Departments of Medicine and Biochemistry and Biomedical Sciences, McMaster University, and Executive Director, Thrombosis & Atherosclerosis Research Institute. "The FDA’s approval of the 10 mg dose of Xarelto for preventing recurrent VTE, along with clinical evidence confirming the superiority of Xarelto over aspirin for extended VTE prevention, means we can finally put this debate to rest."
The FDA’s approval of the Xarelto 10 mg once-daily dose was based on the EINSTEIN CHOICE study results. The EINSTEIN CHOICE study evaluated patients with VTE who were already treated with six to 12 months of initial anticoagulation therapy and then received Xarelto 10 mg once daily, Xarelto 20 mg once daily or aspirin 100 mg once daily for up to an additional 12 months of treatment. Patients taking either Xarelto dose had significantly fewer recurrent VTE compared to those taking aspirin. Specifically, Xarelto 10 mg reduced the risk of recurrent VTE by 74 percent and Xarelto 20 mg by 66 percent. All three treatment groups had low rates of major bleeding (0.4 percent with Xarelto 10 mg, 0.5 percent with Xarelto 20 mg, 0.3 percent with aspirin).
In September 2017, Janssen’s development partner Bayer announced the Committee for Medicinal Products for Human Use of the European Medicines Agency granted a positive opinion to update the Xarelto label to include the 10 mg once-daily dose in the European Union; the European Commission granted approval on October 19, 2017.

FDA Approves Auryxia (ferric citrate) Tablets as a Treatment for People with Iron Deficiency Anemia and Chronic Kidney Disease, Not on Dialysis

Keryx Biopharmaceuticals, Inc. (Nasdaq:KERX), a company focused on bringing innovative medicines to people with kidney disease, today announced that the U.S. Food and Drug Administration (FDA) has approved Auryxia for an additional indication. The approval is for the treatment of iron deficiency anemia in adults with chronic kidney disease (CKD), not on dialysis. Auryxia was originally approved in September 2014 for the control of serum phosphorus levels in people with chronic kidney disease who require dialysis.

FERRIC CITRATE.png
With the new indication, millions of people living with chronic kidney disease have the potential to benefit from treatment with Auryxia. This medication is available today in pharmacies and covered broadly by Medicare Part D and commercial insurance providers in the United States.
“More than half of the approximate 30 million people in the United States living with chronic kidney disease are iron deficient, and yet, this is the only tablet that has been developed and approved specifically to address iron deficiency anemia in these patients, who are not on dialysis,” said Steven Fishbane, M.D., chief, division of kidney diseases and hypertension, department of medicine, Northwell Health in Great Neck, New York. “Starting today, physicians can prescribe an oral iron medicine to help people living with this condition, the majority of whom are not being optimally treated.”

Wednesday, November 29, 2017

Allergan Receives FDA Approval for Vraylar (cariprazine) in the Maintenance Treatment of Schizophrenia

In continuation of my update on Cariprazine

Cariprazine.svg

Allergan plc (NYSE: AGN)  announced that the U.S. Food and Drug Administration (FDA) has approved the supplemental New Drug Application (sNDA) for Vraylar (cariprazine) for the maintenance treatment of adults with schizophrenia. Vraylar is also approved in the U.S. in adults for the acute treatment of schizophrenia and acute treatment of manic or mixed episodes of bipolar I disorder.

"Schizophrenia is one of the most challenging mental health disorders to manage – particularly due to the complexity of patient symptoms, varying response to treatment and high rates of relapse," said Dr. Herbert Meltzer, Professor of Psychiatry and Behavioral Sciences at Northwestern Feinberg School of Medicine. "The goal of clinicians is to minimize relapses, which can cause significant personal distress, and can often have serious implications for a patient's health. The approval of Vraylar for the maintenance treatment of schizophrenia provides an important therapy for patients and physicians who are in need of long-term treatment options."
Without maintenance treatment, 60 – 70 percent of schizophrenia patients relapse within one year. Once a schizophrenia patient reaches the stable or maintenance phase of treatment, it is important for the physician to develop a long-term treatment management plan to minimize relapse risk, monitor for and reduce severity of side effects, and address residual symptoms where possible.2
The efficacy of Vraylar in the maintenance treatment of schizophrenia was based on an up to 72-week, multinational, double-blind, placebo-controlled, randomized withdrawal study in the prevention of relapse in adult patients with schizophrenia. The study included a 20-week open-label phase where patients with schizophrenia were treated with cariprazine 3, 6 or 9 mg per day. Patients who responded and met the stabilization criteria during the open-label period were then randomized either to continue their Vraylar dose (3, 6 or 9 mg per day) or be switched to placebo for up to 72 weeks or until a relapse occurred. The primary endpoint was time to relapse during the randomized, double blind phase.1 The study demonstrated that Vraylar significantly delayed the time to relapse compared to placebo (P=0.0010). Relapse occurred in nearly twice as many placebo-treated patients (49.5%, n=49/99) as Vraylar-treated (29.7%, n=30/101) patients. The safety results were consistent with the profile observed to-date for Vraylar.
"The differences in how people with schizophrenia respond to treatment underscores the importance of having additional treatment options," said David Nicholson, Chief Research & Development Officer at Allergan. "We are pleased that the FDA has recognized the benefits of Vraylar for maintenance treatment of adults with schizophrenia. This approval demonstrates our continued investment in Vraylar, as well as our commitment to developing treatments that address unmet needs facing people living with mental illness."

Monday, November 27, 2017

FDA Approves Abilify MyCite (aripiprazole) Pill with Sensor to Digitally Track if Patients Have Ingested Their Medication

In continuation of my update on  aripiprazole 

Structural formula of aripiprazole

The U.S. Food and Drug Administration today approved the first drug in the U.S. with a digital ingestion tracking system. Abilify MyCite (aripiprazole tablets with sensor) has an ingestible sensor embedded in the pill that records that the medication was taken. The product is approved for the treatment of schizophrenia, acute treatment of manic and mixed episodes associated with bipolar I disorder and for use as an add-on treatment for depression in adults.

The system works by sending a message from the pill’s sensor to a wearable patch. The patch transmits the information to a mobile application so that patients can track the ingestion of the medication on their smart phone. Patients can also permit their caregivers and physician to access the information through a web-based portal.
“Being able to track ingestion of medications prescribed for mental illness may be useful for some patients,” said Mitchell Mathis, M.D., director of the Division of Psychiatry Products in the FDA’s Center for Drug Evaluation and Research. “The FDA supports the development and use of new technology in prescription drugs and is committed to working with companies to understand how technology might benefit patients and prescribers.”
It is important to note that Abilify MyCite’s prescribing information (labeling) notes that the ability of the product to improve patient compliance with their treatment regimen has not been shown. Abilify MyCite should not be used to track drug ingestion in “real-time” or during an emergency because detection may be delayed or may not occur.
Schizophrenia is a chronic, severe and disabling brain disorder. About 1 percent of Americans have this illness. Typically, symptoms are first seen in adults younger than 30 years of age. Symptoms of those with schizophrenia include hearing voices, believing other people are reading their minds or controlling their thoughts, and being suspicious or withdrawn. Bipolar disorder, also known as manic-depressive illness, is another brain disorder that causes unusual shifts in mood, energy, activity levels and the ability to carry out day-to-day tasks. The symptoms of bipolar disorder include alternating periods of depression and high or irritable mood, increased activity and restlessness, racing thoughts, talking fast, impulsive behavior and a decreased need for sleep.
Abilify MyCite contains a Boxed Warning alerting health care professionals that elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Abilify MyCite is not approved to treat patients with dementia-related psychosis. The Boxed Warning also warns about an increased risk of suicidal thinking and behavior in children, adolescents and young adults taking antidepressants. The safety and effectiveness of Abilify MyCite have not been established in pediatric patients. Patients should be monitored for worsening and emergence of suicidal thoughts and behaviors. Abilify MyCite must be dispensed with a patient Medication Guide that describes important information about the drug’s uses and risks.
In the clinical trials for Abilify, the most common side effects reported by adults taking Abilify were nausea, vomiting, constipation, headache, dizziness, uncontrollable limb and body movements (akathisia), anxiety, insomnia, and restlessness. Skin irritation at the site of the MyCite patch placement may occur in some patients.
Prior to initial patient use of the product, the patient’s health care professional should facilitate use of the drug, patch and app to ensure the patient is capable and willing to use the system.
Abilify was first approved by the FDA in 2002 to treat schizophrenia. The ingestible sensor used in Abilify MyCite was first permitted for marketing by the FDA in 2012.

Friday, November 24, 2017

Newly discovered drug-like compound may revolutionize treatment of autoimmune diseases

Figure 1

University of Colorado Boulder researchers have discovered a potent, drug-like compound that could someday revolutionize treatment of rheumatoid arthritis and other autoimmune diseases by inhibiting a protein instrumental in prompting the body to start attacking its own tissue.
"We have discovered a key to lock this protein in a resting state," said Hang Hubert Yin, a biochemistry professor in the BioFrontiers Institute and lead author of a paper, published today in Nature Chemical Biology, describing the discovery. "This could be paradigm shifting."
More than 23.5 million Americans suffer from autoimmune diseases like rheumatoid arthritis, scleroderma and lupus, in which an overzealous immune response leads to pain, inflammation, skin disorders and other chronic health problems.
Three of the top five selling drugs in the United States aim to ease their symptoms. But no cure exists, and treatments are expensive and come with side effects.
"Given the prevalence of these diseases, there is a big push for alternatives," Yin said.
For years, scientists have suspected that a protein called Toll-like receptor 8 (TLR8) plays a key role in the innate immune response. When it senses the presence of a virus or bacteria, it goes through a series of steps to transform from its passive to active state, triggering a cascade of inflammatory signals to fight off the foreign invader. But, as Yin explained, "it can be a double-edged sword" leading to disease when that response is excessive.
Because TLR8 has a unique molecular structure and is hidden inside the endosome -- an infinitesimal bubble inside the cell -- rather than on the cell's surface, it has proven an extremely difficult target for drug development.
"This is a long-sought-after target with very little success," Yin said.
But his study shows a drug-like molecule called CU-CPT8m binds to and inhibits TLR8 and exerts "potent anti-inflammatory effects" on the tissue of patients with arthritis, osteoarthritis and Still's disease, a rare autoimmune illness.
For the study, Yin and his co-authors used high-throughput screening to look through more than 14,000 small molecule compounds to determine whether they had the right chemical structure to bind to TLR8. They identified four that shared a similar structure.
Using that structure as a model, they chemically synthesized hundreds of novel compounds in an effort to find one that perfectly bound to and inhibited TLR8.
Previous efforts to target the protein have focused on shutting it down when it is in its active state. But the compound Yin discovered prevents it from activating while still in its passive state.
"Before, people were trying to close the open door to shut it down. We found the key to lock the door from the inside so it never opens," Yin said.
Much more research is necessary, but that could lead to treatments that strike at the root cause of autoimmune diseases, rather than just treating symptoms.
With help from CU's Technology Transfer Office, Yin has already filed a patent application and hopes to move on to animal studies and clinical trials within the next two years.
In the meantime, the new compound can serve as a first-of-its kind tool to understand exactly what TLR8 and the other nine toll-like receptors do in the body.
"Our study provides the first small molecule tool to shut this protein down so we can understand its pathogenesis," Yin said.
Ref : https://www.colorado.edu/today/2017/11/20/arthritis-autoimmune-disease-discovery-could-lead-new-treatments


Thursday, November 23, 2017

Multiple sclerosis drug can beat obstinate bacteria

In continuation of my update on glatiramer
Encountering bacteria with innocent names such as Pseudomonas aeruginosa and Enterobacteriaceae can lead to hospitalization and - in a worst-case scenario - can also be life-threatening. The bacteria, which cause infections such as pneumonia, frequently develop multi-resistance towards classic antibiotics.
Researchers from Aarhus University have discovered that a drug known as glatiramer acetate, which is normally used for treating the disease multiple sclerosis, has a hitherto unknown effect on obstinate bacteria.
Laboratory experiments have shown that the drug kills half of the Pseudomonas bacteria in specimens from patients with cystic fibrosis who are often exposed to the bacteria in the lungs.
The research results have recently been published in the scientific journal Scientific Reports.
The discovery is good news at a time where multi-resistant bacteria are a growing problem.
"We see great perspectives in the discovery because our data shows that the drug is effective against infections that occur because of what are known as Gram-negative bacteria. These bacteria form the basis of diseases such as pneumonia, cystitis and septic shock. Due to growing resistance, we are experiencing a decline in the number of effective treatments against them, and some of the medicaments which we otherwise know to be effective must be given in such high doses to be effective that they become toxic for the patients," explains Professor with special responsibilities (MSO) Thomas Vorup-Jensen from the Department of Biomedicine at Aarhus University.
According to a British survey commissioned by the British government, in 2050 resistant bacteria will all-in-all kill more people around the world than cancer. Neither the pharmaceutical industry or researchers have so far succeeded in developing new types of antibiotics that can beat the bacteria following classic strategies for the development of new medicines.

Methotrexate drug holiday improves flu vaccine efficacy in rheumatoid arthritis patients


In continuation of my update on methotrexate


Methotrexate skeletal.svg

People with RA who stop taking methotrexate treatment for just two weeks after they have a seasonal flu shot can improve the vaccine's efficacy without increasing RA disease activity, according to new research findings presented this week at the 2017 ACR/ARHP Annual Meeting in San Diego.


Rheumatoid arthritis (RA) is a chronic disease that causes   pain,  stiffness,  welling, and limitation in the motion and function of multiple joints. Though joints are the principal body parts affected by RA, inflammation can develop in other organs as well. An estimated 1.3million Americans have RA, and the disease typically affects women twice as often as men.


Methotrexate, a widely used immunosuppressant, can lower vaccine efficacy in people with RA. So researchers in Seoul, Republic of Korea, set out to investigate whether patients with RA could improve their response to influenza vaccinations by temporarily pausing methotrexate use for two weeks after their flu shot.


"RA patients are more susceptible to infections, including seasonal flu, due to their underlying abnormal immune function and the treatment-associated immune suppression," said Jin Kyun Park, MD, Assistant Professor of Medicine at Seoul National University Hospital, and a lead author of the study. "RA patients taking methotrexate are at even higher risk of infection and infection-related complications, so it's important that they be vaccinated against preventable infectious diseases. However, the immune suppression decreases vaccine response.
To overcome this shortcoming, our group has been working on a novel immunization protocol for RA patients to optimize vaccine response,  including increasing immunogenicity of flu vaccines."

In this prospective, multicenter, randomized, parallel-group trial conducted from October 2016 to January 2017, 316 RA patients who were taking a stable methotrexate dose were randomly assigned to two groups: 156 continued their regular methotrexate and 160 discontinued their dose for two weeks after receiving their flu shot. All participants were vaccinated with a seasonal, quadrivalent influenza vaccine containing H1N1, H3N2, B-Yamagata and B-Victoria.


Wednesday, November 22, 2017

FDA Approves Juluca, First Two-Drug Regimen for HIV Patients

In continuation of my updates on dolutegravir and rilpivirine,
The FDA has approved the first complete treatment regimen containing only two drugs to treat certain adults with human immunodeficiency virus type 1 (HIV-1) instead of the three or more drugs included in standard HIV treatment.

Juluca (dolutegravir/rilpivirine, ViiV Healthcare) is a fixed-dose tablet approved to treat adults with HIV-1 infections whose virus is currently suppressed (HIV-1 RNA less than 50 copies per mL) on a stable regimen for at least six months, with no history of treatment failure and no known substitutions associated with resistance to the individual components of the new combination. Dolutegravir 50 mg (ViiV Healthcare) is an integrase strand transfer inhibitor, and rilpivirine 25 mg (Janssen Therapeutics) is a non-nucleoside reverse transcriptase inhibitor.
Rilpivirine.svg rilpivirine    Dolutegravir.svg Dolutegravir
 “Limiting the number of drugs in any HIV treatment regimen can help reduce toxicity for patients,” said Debra Birnkrant, MD, director of the Division of Antiviral Products in the FDA’s Center for Drug Evaluation and Research.
HIV weakens a person’s immune system by destroying important cells that fight disease and infection. According to the Centers for Disease Control and Prevention, an estimated 1.1 million people in the United States are living with HIV, and the disease remains a significant cause of death for certain populations.
This FDA approval is based primarily on data from two pivotal phase 3 clinical trials, SWORD-12 and SWORD-2,2 which showed the two-drug regimen achieved non-inferior viral suppression (HIV-1 RNA less than 50 copies per mL) at 48 weeks compared with patients’ three- or four-drug current antiretroviral regimen (CAR) in both pooled and individual analyses of the SWORD-1 and SWORD-2 studies (dolutegravir/rilpivirine 486/513 [95%], CAR 485/511 [95%]; adjusted difference, –0.2%; 95% confidence interval, –3.0% to  2.5%, pooled analysis). Virological suppression rates were similar between treatment arms. Drug related adverse events and adverse events leading to withdrawal occurred in low frequencies in both arms of the study, but more frequently in the investigational arm.
The most common side effects in patients taking Juluca were diarrhea and headache. Serious side effects include skin rash and allergic reactions, liver problems, and depression or mood changes. Juluca should not be given with other anti-HIV drugs and may have drug interactions with other commonly used medications.
Ref : https://www.viivhealthcare.com/media/press-releases/2017/november/viiv-healthcare-announces-us-fda-approval-for-juluca.aspx

New findings on tolvaptan as autosomal dominant polycystic kidney disease treatment

 In continuation of my update on tolvaptan

(RS)-Tolvaptan Structural Formula V1.svg

A phase 3 trial studying the effects of tolvaptan has found that the drug slowed the rate of decline in kidney function in patients with the most common form of polycystic kidney disease, a condition with no cure. The results are published today in the New England Journal of Medicine.

Autosomal dominant polycystic kidney disease is an inheritedcondition that affects 1 in every 500 to 1,000 individuals in the U.S.This disease is found in all races and sexes.

Autosomal dominant polycystic kidney disease, which is the fourth most common cause of end-stage kidney disease, requires dialysis orkidney transplant.

The disease causes a slow but relentless growth of cysts that damage the kidneys. In addition to negatively affecting quality of life, thecondition also causes hypertension and painful complications. The cysts, which can damage kidneys with their size, can develop in other organs,especially the liver.

Approximately half of individuals with autosomal dominant polycystic kidney disease eventually will require dialysis or kidney transplant by age 60. The results of the trial demonstrated tolvaptan's ability to intervene in a way that slows kidney function decline in this population.

"This is the first treatment that targets a mechanism that directlycontributes to the development and growth of the kidney cysts inautosomal dominant polycystic kidney disease," says Vicente Torres, M.D., Ph.D., director of Mayo Clinic's Translational Polycystic Kidney Disease Center. "This in effect means it may delay the need for a kidney transplant or dialysis in patients with this disease."

Tuesday, November 21, 2017

Omega-3 and Omega-6 fatty acid intake may affect lupus outcomes



 omega 3


In continuation of my update on omega fatty acids

Higher intake of omega-3 fatty acids was associated with better sleep quality and a decrease in depressive symptoms in lupus patients, among other patient-reported outcomes, according to new research findings presented this week at the 2017 ACR/ARHP Annual Meeting in San Diego. 


Lupus is a chronic (long-term) inflammatory autoimmune disease in which an unknown trigger causes the body's immune system to attack its own healthy tissues. The most common type of lupus is systemic lupus erythematosus (SLE), a complex, multiple symptom disease that can cause inflammation, pain and damage to various parts of the body. While anyone can develop lupus, it occurs 9-10 times more often in women than in men, and is 2-3 times more common among women of color.

Omega fatty acids have an effect on inflammation in the body, with omega-3 fatty acids generally acting as an anti-inflammatory and omega-6 fatty acids acting as a pro-inflammatory. Western diets are often much higher in omega-6fatty acids, and they are suspected to contribute to chronic diseases.



While small studies show an association between omega-3 supplementation and reduced disease activity in lupus patients. Researchers at the University of Michigan in Ann Arbor examined their impact on patient-reported outcomes, or PROs. They performed a population-based, cross-sectional study to look for a possibleassociation between dietary intake of omega-3 and omega-6 fatty acidsand PROs in lupus patients. Data from the Michigan Lupus Epidemiology & Surveillance (MILES) program was used.

"Western diets are thought to contribute to an increase in people with chronic conditions including autoimmune diseases. Many small studies found that omega-3 supplementation was associated with an improvement in disease activity in SLE patients, but no studies have looked at omega-3 exposure through diet or its impact on PROs," said Prae Charoenwoodhipong, MS, a graduate student in the Department of
Nutrition Science at the University of Michigan School of Public Health in Ann Arbor. "Also, very few studies have looked at the impact of omega-6, an inflammatory fatty acid that is very common in U.S. diets. According to rheumatologists I've worked with, patients with SLE are always asking about what they might be able to do with supplements or their diet to help improve their health."

Omega-3 and Omega-6 fatty acid intake may affect lupus outcomes

Friday, November 17, 2017

Onalespib could be an effective treatment for glioblastoma, preclinical studies show





AT13387.png

The targeted therapy onalespib has shown effectiveness in preclinical studies of glioblastoma by researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute.

Onalespib is designed to inhibit a molecule called HSP90. The molecule helps newly made protein molecules fold into their final functional form. A large number of receptor and DNA-damage-response proteins require HSP90 to achieve their functional conformation. In cancer cells, HSP90 can be expressed up to 10 times higher than in normal cells.

This study showed that onalespib blocked HSP90 activity and thereby reduced the expression of cell-survival proteins such as AKT and endothelial growth factor receptor in several glioma cell lines and in glioma stem cells obtained from patient tumors. This, in turn, reduced the survival, proliferation, invasion and migration of the cells.

In animal models of glioblastoma (GBM), the agent crossed the blood-brain barrier, and showed effectiveness as a single agent, and then greater effectiveness in combination with temozolomide, improving survival in both cases.
The findings are published in the journal Clinical Cancer Research.

"Our studies show that onalespib can efficiently breach the blood-brain barrier and reach tumor cells better than other HSP90 inhibitors," says principal investigator Vinay Puduvalli, MD, professor and director of the Division of Neuro-Oncology at Ohio State and a clinician-researcher at the OSUCCC – James.

"By inhibiting HSP90, onalespib disrupts several key signaling pathways that drive the proliferation, metastasis and survival of glioblastoma cells. These findings suggest that this agent, in combination with chemotherapeutic temozolomide, could be an exciting new therapy for GBM. Based on the results of this study, we have generated a clinical trial that will determine whether onalespib in combination with standard therapy is safe and effective in patients with newly diagnosed glioblastoma," he says.

Glioblastoma is the most common and deadly form of brain cancer. More than 12,000 new cases are expected to be diagnosed in 2017, with overall survival averaging 16-18 months. The disease remains incurable, largely because GBM is difficult to remove surgically, because the blood-brain barrier prevents most chemotherapy from reaching these tumors and because these tumors tend to be radiation resistant.

The study's key findings include:
  • Onalespib levels were higher in brain tissue compared with plasma after intravenous administration in a mouse model, showing that the agent can cross the blood-brain barrier.
  • Tumor cells derived from patients and implanted into a mouse model showed that onalespib plus temozolomide significantly survival compared with mice treated with a neutral agent or either agent alone.
 Ref : https://medicalxpress.com/journals/clinical-cancer-research/


Thursday, November 16, 2017

Drug 'melts away' fat inside arteries


Trodusquemine.svg 


 A new drug being trialled for treating breast cancer and diabetes has been shown to 'melt away' the fat inside arteries that can cause heart attacks and  strokes. Researchers fromthe University of Aberdeen, using pre-clinical mouse models, showedthat just a single dose of the drug (Trodusquemine) completely reversedthe effects of a disease that causes a host of heart problems.

Atherosclerosis is the build-up of fatty material inside the arteries. Over time this fatty material can grow bigger until your arteries become so narrow that not enough blood can pass through.

Atherosclerosis is the condition that causes most heart attacks and strokes. In pre-clinical tests, mice with set-in atherosclerosis, mimicking what happens in humans, had less fatty plaques in their arteries whether they had regular doses over time or just a single dose of Trodusquemine.

The drug works by stopping an enzyme called PTP1B, which is normally increased in people with obesity or diabetes and conditions involving prolonged inflammation such as sepsis, inflamed diabetic foot ulcers and allergic lung inflammation. The researchers found that it also stimulated the action of another protein (AMPK), which effectively mimics exercise and reduces chronic inflammation.

It has already been shown to be effective with diabetes and breast cancer patients but this is the first time the drug has been shown to have benefits for long-term cardiovascular disease.

The £236,000 study was funded by the British Heart Foundation. Professor Mirela Delibegovic and Dr Dawn Thompson from the University of Aberdeen's Institute of Medical Sciences who led the study said:

"All humans have some level of atherosclerosis. As you age you start to
develop these fatty streaks inside your arteries. It is a big problem
for people who are overweight or have underlying cardiovascular
conditions."

"Trodusquemine has already been trialled for treatment of diabetes and breast cancer but this is the first time it has been used in models of atherosclerosis. 

"These have only been tested at pre-clinical level, in mice, so far but the results were quite impressive and showed that just a single dose of this drug seemed to completely reverse the effects of arthrosclerosis.

"The next step is to test the ability of this drug to improve outcomes in human patients with developed atherosclerosis and cardiovascular disease".

Professor Jeremy Pearson, Associate Medical Director at the British Heart Foundation, said: "Trodusquemine is in early clinical trials for the treatment of diabetes. This study shows it can also limit the build-up of fatty atherosclerotic plaques in mice. If we see the same effect in patients, the drug may prove even more useful than currently hoped for.





 Ref : https://pubchem.ncbi.nlm.nih.gov/compound/Trodusquemine#section=2D-Structure

https://www.abdn.ac.uk/news/11280/







Drug 'melts away' fat inside arteries

Wednesday, November 15, 2017

AZD6738 found to slow some types of children's tumor growth in mouse models

Prior research has shown that cancer in children is very seldom the same as  cancer in adults—in many cases, tumors that grow in children differ markedly from tumors that grow in adults which means they require completely different types of treatment. Unfortunately, treatments for childhood tumors has progressed at a much slower pace than for adults. Just four of them, for example, have been approved for use in the U.S. over the last 25 years. One of the main ways to treat adult tumors is to apply chemicals that serve to actively reduce tumor size, an approach that has not worked well with children. To get around that problem, the researchers with this new effort have been studying a chemical that has shown an ability to stop tumor growth by preventing tumor cells from repairing their DNA.

AZD6738 Chemical Structure

The researchers began by noting that prior research had shown that many types of childhood tumors rely on a DNA pathway called nonhomologous end joining (NHEJ) to survive. That led them to search for a chemical that would disrupt the pathway, preventing the cell from repairing its own DNA. Such tumors, the researchers noted, appear to depend on NHEJ to help them overcome problems with handling the excess amounts of an enzyme called PGBD5 they produce.

After finding that applying the chemical AZD6738 to tumor cells directly prevented them from growing, the team then began testing it in mouse models (mice with human tumor cells implanted in them). They report that doing so caused two types of tumors to stop growing but did not work against two others. While promising, the researchers acknowledge that the chemical is not likely to represent a means for destroying tumors in human patients even if it were to pass clinical trials. It stops growth but does not decrease tumor size. But that would of course still be a far better outcome for treating patients who have no other options. 


AZD6738 found to slow some types of children's tumor growth in mouse models

Tuesday, November 14, 2017

Caffeine consumption may help kidney disease patients live longer

In continuation of my update on caffeine..

2D structure of caffeine
Caffeine consumption may prolong the lives in patients with chronic kidney disease (CKD), according to a study that will be presented at ASN Kidney Week 2017 October 31-November 5 at the Ernest N. Morial Convention Center in New Orleans, LA.  

Coffee consumption has been linked to a longer life in the general population. To see if this holds true for individuals with CKD, Miguel Bigotte Vieira, MD (Centro Hospitalar Lisboa Norte, in Portugal), and his colleagues examined the association of caffeine consumption with mortality among 2328 patients with CKD in a prospective US cohort, using the continuous National Health and Nutrition Examination Survey(NHANES) 1999-2010.

The team found a dose-dependent inverse association between caffeine and all-cause mortality. Compared with those in the lowest quartile of caffeine consumption, those in the second, third, and highest quartiles had 12%, 22%, and 24% lower risks of dying.

"Our study showed a dose-dependent protective effect of caffeine consumption on mortality among patients with CKD. This association was independent of potential confounders including age, gender, race, annual family income, education level, estimated GFR, albumin/creatinine ratio, hypertension, smoking status, dyslipidemia, body mass index, previous cardiovascular events and diet: consumption of alcohol, carbohydrates, polyunsaturated fatty acids, and fibers," said Dr. Bigotte Vieira. 

"These results suggest that advising patients with CKD to drink more caffeine may reduce their mortality. This would represent a simple, clinically beneficial, and inexpensive option, though this benefit should ideally be confirmed in a randomized clinical trial." Dr. Bigotte Vieira stressed that this observational study cannot prove thatcaffeine reduces the risk of death in patients with CKD, but onlysuggests the possibility of such a protective effect.

Friday, November 10, 2017

'Intelligent' nanoparticles could help treat cancer patients




Scientists from the University of Surrey have developed 'intelligent'  nanoparticles which heat up to a temperature high enough to kill  cancerous cells - but which then self-regulate and lose heat before they get hot enough to harm healthy tissue.
The self-stopping nanoparticles could soon be used as part of  hyperthermic-thermotherapy to treat patients with cancer, according to  an exciting new study reported in Nanoscale. Thermotherapy has long been used as a treatment method for cancer, but it is difficult to treat patients without damaging healthy cells. However, tumor cells can be weakened or killed without affecting normal tissue if temperatures can be controlled accurately within a range of 42°C to 45 °C.
This could potentially be a game changer in the way we treat people who have cancer . If we can keep cancer treatment sat at a temperature level high enough to kill the cancer, while low enough to stop harming healthy tissue, it will prevent some of the serious side effects of vital treatment.
It's a very exciting development which, once again, shows that the University of Surrey research is at the forefront of nanotechnologies - whether in the field of energy materials or, in this case, healthcare. Dr. Wei Zhang, Associate Professor from Dalian University of Technology said Magnetic induced hyperthermia is a traditional route of treating  malignant tumors. However, the difficulties in temperature control has significantly restricted its usage If we can modulate the magnetic  properties of the nanoparticles, the therapeutic temperature can be  self-regulated, eliminating the use of clumsy temperature monitoring and controlling systems.
By making magnetic materials with the Curie temperature falling in the range of hyperthermia temperatures, the self-regulation of therapeutics can be achieved. For the most magnetic materials, however,  the Curie temperature is much higher than the human body can endure. By  adjusting the components as we have, we have synthesized the nanoparticles with the Curie temperature as low as 34 °C. This is a major nanomaterials breakthrough.

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