Compound reverses symptoms of Alzheimer's disease in mice

"It reversed learning and memory deficits and brain inflammation in mice that are genetically engineered to model Alzheimer's disease," Farr said. "Our current findings suggest that the compound, which is called antisense oligonucleotide (OL-1), is a potential treatment for Alzheimer's disease."

Farr cautioned that the experiment was conducted in a mouse model. Like any drug, before an antisense compound could be tested in human clinical trials, toxicity tests need to be completed.

Antisense is a strand of molecules that bind to messenger RNA, launching a cascade of cellular events that turns off a certain gene.

In this case, OL-1 blocks the translation of RNA, which triggers a process that keeps excess amyloid beta protein from being produced. The specific antisense significantly decreased the over expression of a substance called amyloid beta protein precursor, which normalized the amount of amyloid beta protein in the body. Excess amyloid beta protein is believed to be partially responsible for the formation of plaque in
the brain of patients who have Alzheimer's disease.

Scientists tested OL-1 in a type of mouse that overexpresses a mutant form of the human amyloid beta precursor gene. Previously they had tested the substance in a mouse model that has a natural mutation causing it to overproduce mouse amyloid beta. Like people who have Alzheimer's disease, both types of mice have age-related impairments in learning and memory, elevated levels of amyloid beta protein that stay in the brain and increased inflammation and oxidative damage to the hippocampus  the part of the brain responsible for learning and memory.

"To be effective in humans, OL-1 would need to be effective at suppressing production of human amyloid beta protein," Farr said.

Scientists compared the mice that were genetically engineered to overproduce human amyloid beta protein with a wild strain, which served as the control. All of the wild strain received random antisense, while about half of the genetically engineered mice received random antisense and half received OL-1. 

The mice were given a series of tests designed to measure memory, learning and appropriate behavior, such as going through a maze, exploring an unfamiliar location and recognizing an object. 

Scientists found that learning and memory improved in the genetically engineered mice that received OL-1 compared to the genetically engineered mice that received random antisense. Learning and memory were the same among genetically engineered mice that received OL-1 and wild mice that received random antisense.

They also tested the effect of administering the drug through the central nervous system, so it crossed the blood brain barrier to enter the brain directly, and of giving it through a vein in the tail, so it circulated through the bloodstream in the body. They found where the drug was injected had little effect on learning and memory.

Ref http://iospress.metapress.com/content/px72758w0158103u/?issue=4&genre=article&spage=1005&issn=1387-2877&volume=40

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Compound
reverses symptoms of Alzheimer's disease in mice  

FDA Approves Purixan (mercaptopurine) Oral Suspension

U. S. Food and Drug Administration approved an oral suspension of mercaptopurine (Purixan, NOVA Laboratories Limited). Mercaptopurine is a 20 mg/ml oral suspension. Purixan is indicated for the treatment of patients with acute lymphoblastic leukemia (ALL) as part of a combination regimen..

FDA Approves Purixan (mercaptopurine) Oral Suspension

Scientists have found a potential cure for Ebola (Science Alert)

Ebola and related viruses cause hemorrhagic fever and death through organ failure, and can have a mortality rate of up to 90%, among the highest of any known human disease.  But researchers working in a high-contaminant biological laboratory maintained by USAMRIID at Fort Detrick in Maryland, US, may have found a potential cure.

The scientists have discovered a molecule, named BCX4430, (see structure) which looks a lot like the "A" that makes up DNA: adenosine. Adenosine is one of four base pairs in DNA, and is also used in the genomes of RNA-based viruses,  such as Ebola. But because BCX4430 looks so much like Adenosine, the scientists found that members of the Filoviridae virus family, such as Ebola, can accidentally use it as a building block when trying to grow inside our cells

  
In the study, the team gave Macaque monkeys effected with the deadly Marburg virus (a close relative to Ebola) two doses for BCX4430 a day  for 14 days.

The monkeys who weren't given any of the treatment were dead by day 12, whereas all but one monkey who was given BCX4430 survived, even if they only received treatment 48 hours after they were infected.

Luckily, only virus cells appear to be tricked into using BCX4430, and human and monkey cells do just fine with the molecule around. In vitro experiments
also suggest that BCX4430 could potentially be used against a wide range of
viruses, including SARS, influenza, measles and dengue.
It's too early to get excited just yet, with no human trials yet conducted. But the newly discovered molecule holds the greatest potential we've ever seen for curing these terrifying diseases.

http://www.nature.com/nature/journal/vaop/ncurrent/fig_tab/nature13027_F1.html

Scientists
have found a potential cure for Ebola (Science Alert)

MSU research pushes promising molecule toward clinical trials for treatment of neurological disorders

Research at Michigan State University, published in the Journal of Biological Chemistry, shows that a small "molecular tweezer" keeps proteins from clumping, or aggregating, the first step of neurological disorders such as Parkinson's disease, Alzheimer's disease and Huntington's disease.

The results are pushing the promising molecule toward clinical trials and actually becoming a new drug, said Lisa Lapidus, MSU associate professor of physics and astronomy and co-author of the paper.

"By the time patients show symptoms and go to a doctor, aggregation already has a stronghold in their brains," she said. "In the lab, however, we can see the first steps, at the very place where the drugs could be the most effective. This could be a strong model for fighting Parkinson's and other diseases that involve neurotoxic aggregation."

Lapidus' lab uses lasers to study the speed of protein reconfiguration before aggregation, a technique Lapidus pioneered. Proteins are chains of amino acids that do most of the work in cells. Scientists understand protein structure, but they don't know how they are built - a process known as folding.

Lapidus' lab has shed light on the process by correlating the speed at which an unfolded protein changes shape, or reconfigures, with its tendency to clump or bind with other proteins. If reconfiguration is much faster or slower than the speed at which proteins bump into each other, aggregation is slow, but if reconfiguration is the same speed, aggregation is fast. 

Srabasti Acharya, lead author and doctoral candidate in Lapidus' lab, tested the molecule, CLR01, (see structure) which was patented jointly by researchers at the University of Duisburg-Essen (Germany) and UCLA. CLR01 binds to the protein and prevents aggregation by speeding up reconfiguration. It's like a claw that attaches to the amino acid lysine, which is part of the protein.

This work was preceded by Lapidus' research involving the spice curcumin. While the spice molecules put the researchers on a solid path, the molecules weren't viable drug candidates because they cannot cross the blood-brain barrier, or BBB, the filter that controls what chemicals reach the brain.

MSU research pushes promising molecule toward clinical trials for treatment of neurological disorders

MSU research pushes promising molecule toward clinical trials for treatment of neurological disorders

Research at Michigan State University, published in the Journal of Biological Chemistry, shows that a small "molecular tweezer" keeps proteins from clumping, or aggregating, the first step of neurological disorders such as Parkinson's disease, Alzheimer's disease and Huntington's disease.

The results are pushing the promising molecule toward clinical trials and actually becoming a new drug, said Lisa Lapidus, MSU associate professor of physics and astronomy and co-author of the paper.

"By the time patients show symptoms and go to a doctor, aggregation already has a stronghold in their brains," she said. "In the lab, however, we can see the first steps, at the very place where the drugs could be the most effective. This could be a strong model for fighting Parkinson's and other diseases that involve neurotoxic aggregation."

Lapidus' lab uses lasers to study the speed of protein reconfiguration before aggregation, a technique Lapidus pioneered. Proteins are chains of amino acids that do most of the work in cells. Scientists understand protein structure, but they don't know how they are built - a process known as folding.

Lapidus' lab has shed light on the process by correlating the speed at which an unfolded protein changes shape, or reconfigures, with its tendency to clump or bind with other proteins. If reconfiguration is much faster or slower than the speed at which proteins bump into each other, aggregation is slow, but if reconfiguration is the same speed, aggregation is fast. 

Srabasti Acharya, lead author and doctoral candidate in Lapidus' lab, tested the molecule, CLR01, (see structure) which was patented jointly by researchers at the University of Duisburg-Essen (Germany) and UCLA. CLR01 binds to the protein and prevents aggregation by speeding up reconfiguration. It's like a claw that attaches to the amino acid lysine, which is part of the protein.

This work was preceded by Lapidus' research involving the spice curcumin. While the spice molecules put the researchers on a solid path, the molecules weren't viable drug candidates because they cannot cross the blood-brain barrier, or BBB, the filter that controls what chemicals reach the brain.

MSU research pushes promising molecule toward clinical trials for treatment of neurological disorders

MSU research pushes promising molecule toward clinical trials for treatment of neurological disorders

Research at Michigan State University, published in the Journal of Biological Chemistry, shows that a small "molecular tweezer" keeps proteins from clumping, or aggregating, the first step of neurological disorders such as Parkinson's disease, Alzheimer's disease and Huntington's disease.

The results are pushing the promising molecule toward clinical trials and actually becoming a new drug, said Lisa Lapidus, MSU associate professor of physics and astronomy and co-author of the paper.

"By the time patients show symptoms and go to a doctor, aggregation already has a stronghold in their brains," she said. "In the lab, however, we can see the first steps, at the very place where the drugs could be the most effective. This could be a strong model for fighting Parkinson's and other diseases that involve neurotoxic aggregation."

Lapidus' lab uses lasers to study the speed of protein reconfiguration before aggregation, a technique Lapidus pioneered. Proteins are chains of amino acids that do most of the work in cells. Scientists understand protein structure, but they don't know how they are built - a process known as folding.

Lapidus' lab has shed light on the process by correlating the speed at which an unfolded protein changes shape, or reconfigures, with its tendency to clump or bind with other proteins. If reconfiguration is much faster or slower than the speed at which proteins bump into each other, aggregation is slow, but if reconfiguration is the same speed, aggregation is fast. 

Srabasti Acharya, lead author and doctoral candidate in Lapidus' lab, tested the molecule, CLR01, (see structure) which was patented jointly by researchers at the University of Duisburg-Essen (Germany) and UCLA. CLR01 binds to the protein and prevents aggregation by speeding up reconfiguration. It's like a claw that attaches to the amino acid lysine, which is part of the protein.

This work was preceded by Lapidus' research involving the spice curcumin. While the spice molecules put the researchers on a solid path, the molecules weren't viable drug candidates because they cannot cross the blood-brain barrier, or BBB, the filter that controls what chemicals reach the brain.

MSU research pushes promising molecule toward clinical trials for treatment of neurological disorders

MSU research pushes promising molecule toward clinical trials for treatment of neurological disorders

Research at Michigan State University, published in the Journal of Biological Chemistry, shows that a small "molecular tweezer" keeps proteins from clumping, or aggregating, the first step of neurological disorders such as Parkinson's disease, Alzheimer's disease and Huntington's disease.

The results are pushing the promising molecule toward clinical trials and actually becoming a new drug, said Lisa Lapidus, MSU associate professor of physics and astronomy and co-author of the paper.

"By the time patients show symptoms and go to a doctor, aggregation already has a stronghold in their brains," she said. "In the lab, however, we can see the first steps, at the very place where the drugs could be the most effective. This could be a strong model for fighting Parkinson's and other diseases that involve neurotoxic aggregation."

Lapidus' lab uses lasers to study the speed of protein reconfiguration before aggregation, a technique Lapidus pioneered. Proteins are chains of amino acids that do most of the work in cells. Scientists understand protein structure, but they don't know how they are built - a process known as folding.

Lapidus' lab has shed light on the process by correlating the speed at which an unfolded protein changes shape, or reconfigures, with its tendency to clump or bind with other proteins. If reconfiguration is much faster or slower than the speed at which proteins bump into each other, aggregation is slow, but if reconfiguration is the same speed, aggregation is fast. 

Srabasti Acharya, lead author and doctoral candidate in Lapidus' lab, tested the molecule, CLR01, (see structure) which was patented jointly by researchers at the University of Duisburg-Essen (Germany) and UCLA. CLR01 binds to the protein and prevents aggregation by speeding up reconfiguration. It's like a claw that attaches to the amino acid lysine, which is part of the protein.

This work was preceded by Lapidus' research involving the spice curcumin. While the spice molecules put the researchers on a solid path, the molecules weren't viable drug candidates because they cannot cross the blood-brain barrier, or BBB, the filter that controls what chemicals reach the brain.

MSU research pushes promising molecule toward clinical trials for treatment of neurological disorders

MSU research pushes promising molecule toward clinical trials for treatment of neurological disorders

Research at Michigan State University, published in the Journal of Biological Chemistry, shows that a small "molecular tweezer" keeps proteins from clumping, or aggregating, the first step of neurological disorders such as Parkinson's disease, Alzheimer's disease and Huntington's disease.

The results are pushing the promising molecule toward clinical trials and actually becoming a new drug, said Lisa Lapidus, MSU associate professor of physics and astronomy and co-author of the paper.

"By the time patients show symptoms and go to a doctor, aggregation already has a stronghold in their brains," she said. "In the lab, however, we can see the first steps, at the very place where the drugs could be the most effective. This could be a strong model for fighting Parkinson's and other diseases that involve neurotoxic aggregation."

Lapidus' lab uses lasers to study the speed of protein reconfiguration before aggregation, a technique Lapidus pioneered. Proteins are chains of amino acids that do most of the work in cells. Scientists understand protein structure, but they don't know how they are built - a process known as folding.

Lapidus' lab has shed light on the process by correlating the speed at which an unfolded protein changes shape, or reconfigures, with its tendency to clump or bind with other proteins. If reconfiguration is much faster or slower than the speed at which proteins bump into each other, aggregation is slow, but if reconfiguration is the same speed, aggregation is fast. 

Srabasti Acharya, lead author and doctoral candidate in Lapidus' lab, tested the molecule, CLR01, (see structure) which was patented jointly by researchers at the University of Duisburg-Essen (Germany) and UCLA. CLR01 binds to the protein and prevents aggregation by speeding up reconfiguration. It's like a claw that attaches to the amino acid lysine, which is part of the protein.

This work was preceded by Lapidus' research involving the spice curcumin. While the spice molecules put the researchers on a solid path, the molecules weren't viable drug candidates because they cannot cross the blood-brain barrier, or BBB, the filter that controls what chemicals reach the brain.

MSU research pushes promising molecule toward clinical trials for treatment of neurological disorders

MSU research pushes promising molecule toward clinical trials for treatment of neurological disorders

Research at Michigan State University, published in the Journal of Biological Chemistry, shows that a small "molecular tweezer" keeps proteins from clumping, or aggregating, the first step of neurological disorders such as Parkinson's disease, Alzheimer's disease and Huntington's disease.

The results are pushing the promising molecule toward clinical trials and actually becoming a new drug, said Lisa Lapidus, MSU associate professor of physics and astronomy and co-author of the paper.

"By the time patients show symptoms and go to a doctor, aggregation already has a stronghold in their brains," she said. "In the lab, however, we can see the first steps, at the very place where the drugs could be the most effective. This could be a strong model for fighting Parkinson's and other diseases that involve neurotoxic aggregation."

Lapidus' lab uses lasers to study the speed of protein reconfiguration before aggregation, a technique Lapidus pioneered. Proteins are chains of amino acids that do most of the work in cells. Scientists understand protein structure, but they don't know how they are built - a process known as folding.

Lapidus' lab has shed light on the process by correlating the speed at which an unfolded protein changes shape, or reconfigures, with its tendency to clump or bind with other proteins. If reconfiguration is much faster or slower than the speed at which proteins bump into each other, aggregation is slow, but if reconfiguration is the same speed, aggregation is fast. 

Srabasti Acharya, lead author and doctoral candidate in Lapidus' lab, tested the molecule, CLR01, (see structure) which was patented jointly by researchers at the University of Duisburg-Essen (Germany) and UCLA. CLR01 binds to the protein and prevents aggregation by speeding up reconfiguration. It's like a claw that attaches to the amino acid lysine, which is part of the protein.

This work was preceded by Lapidus' research involving the spice curcumin. While the spice molecules put the researchers on a solid path, the molecules weren't viable drug candidates because they cannot cross the blood-brain barrier, or BBB, the filter that controls what chemicals reach the brain.

MSU research pushes promising molecule toward clinical trials for treatment of neurological disorders

Penn study clarifies action of potential new class of pain relievers that may benefit and not hurt heart

Penn study clarifies action of potential new class of pain relievers that may benefit and not hurt heart

Cancer drugs block dementia-linked brain inflammation, study finds

A class of drugs developed to treat immune-related conditions and cancer -- including one currently in clinical trials for glioblastoma and other tumors -- eliminates neural inflammation associated with dementia-linked diseases and brain injuries, according to UC Irvine researchers.

In their study, assistant professor of neurobiology & behavior Kim Green and colleagues discovered that the drugs, which can be delivered orally, eradicated microglia, the primary immune cells of the brain. These cells exacerbate many neural diseases, including Alzheimer's and Parkinson's, as well as brain injury.

"Because microglia are implicated in most brain disorders, we feel we've found a novel and broadly applicable therapeutic approach," Green said. "This study presents a new way to not just modulate inflammation in the brain but eliminate it completely, making this a breakthrough option for a range of neuroinflammatory diseases."

The researchers focused on the impact of a class of drugs called CSF1R inhibitors on microglial function. In mouse models, they learned that inhibition led to the removal of virtually all microglia from the adult central nervous system with no ill effects or deficits in behavior or cognition. Because these cells contribute to most brain diseases -- and can harm or kill neurons -- the ability to eradicate them is a powerful advance in the treatment of neuroinflammation-linked disorders.

Green said his group tested several selective CSF1R inhibitors that are under investigation as cancer treatments and immune system modulators. Of these compounds, they found the most effective to be a drug called PLX3397, created by Plexxikon Inc., a Berkeley, Calif.-based biotechnology company and member of the Daiichi Sankyo Group. PLX3397 is currently being evaluated in phase one and two clinical trials for multiple cancers, including glioblastoma, melanoma, breast cancer and leukemia.

Crucially, microglial elimination lasted only as long as treatment continued. Withdrawal of inhibitors produced a rapid repopulation of cells that then grew into new microglia, said Green, who's a member of UC Irvine's Institute for Memory Impairments and Neurological Disorders.

Ref : http://www.cell.com/neuron/abstract/S0896-6273(14)00171-8

Multitarget TB drug could treat other diseases, evade resistance -- ScienceDaily

A drug under clinical trials to treat tuberculosis could be the basis for a class  of broad-spectrum drugs that act against various bacteria, fungal infections and parasites, yet evade resistance, according to a study. The team determined the different ways the drug SQ109 attacks the tuberculosis bacterium, how the drug can be tweaked to target other pathogens from yeast to malaria  and how targeting multiple pathways reduces the probability of pathogens becoming resistant.

Led by U. of I. chemistry professor Eric Oldfield, the team determined the different ways the drug SQ109 attacks the tuberculosis bacterium, how the drug  can be tweaked to target other pathogens from yeast to malaria -- and how targeting multiple pathways reduces the probability of pathogens becoming resistant. SQ109 is made by Sequella Inc., a pharmaceutical company. 

"Drug resistance is a major public health threat," Oldfield said. "We have to make new antibiotics, and we have to find ways to get around the resistance problem. And one way to do that is with multitarget drugs. Resistance in many cases arises because there's a specific mutation in the target protein so the drug will no longer bind. Thus, one possible route to attacking the drug resistance problem will be to devise drugs that don't have just one target, but
two or three targets."

Oldfield read published reports about SQ109 and realized that the drug would likely be multifunctional because it had chemical features similar to those found in other systems he had investigated. The original developers had identified one key action against tuberculosis -- blocking a protein involved in building the cell wall of the bacterium -- but conceded that the drug could have other actions within the cell as well since it was found to kill other bacteria and
fungi that lacked the target protein. Oldfield believed he could identify those actions  and perhaps improve upon SQ109. 

"I was reading Science magazine one day and saw this molecule, SQ109, and I thought, that looks a bit like molecules we've been studying that have multiple targets," Oldfield said. "Given its chemical structure, we thought that some of the enzymes that we study as cancer and antiparasitic drug targets also could be SQ109 targets. We hoped that we could make some analogs that would be more potent against tuberculosis, and maybe even against parasites.

More : http://pubs.acs.org/doi/abs/10.1021/jm500131s

Multitarget TB drug could treat other diseases, evade resistance

Hepatitis C treatment cures over 90 percent of patients with cirrhosis...

Tweelve weeks of an investigational oral therapy cured hepatitis C infection in more than 90 percent of patients with liver cirrhosis and was well tolerated by these patients, according to an international study that included researchers from UT Medicine San Antonio and the Texas Liver Institute. Historically, hepatitis C cure rates in patients with cirrhosis (liver scarring) have been lower than 50 percent and the treatment was not safe for many of these patients.

Hepatitis C treatment cures over 90 percent of patients with cirrhosis  

New molecules working against Alzheimer's discovered -- ScienceDaily

New molecules working against Alzheimer's discovered  

Researchers of the Unit of Medicine Design and Molecular Topology (Department of Physics Chemistry) of the University of Valencia (UV) have discovered eight new active molecules against Alzheimer by a novel mechanism of action, different to the currently used medicines. The work has just been published in PLoS One.

Doxorubicin alone or with ifosfamide for treating soft tissue sarcoma? -- ScienceDaily

IN CONTINUATION OF MY UPDATE ON DOXORUBICIN

Dr. Ian Judson of the Royal Marsden Hospital in London and coordinator of this study says, "Our clinical trial was designed to compare combination treatment with doxorubicin and ifosfamide to treatment with doxorubicin alone, and our results show that the combination chemotherapy did not improve overall survival. So, if the goal of treatment is to control the disease, then administering doxorubicin alone is appropriate. On the other hand, if the goal is to shrink the tumor before another intervention or to relieve symptoms, then combination treatment is justifiable. The observed lack of improvement in overall survival points to the need for better treatments for patients with this disease."

For some thirty years, patients with soft tissue sarcomas have been treated with doxorubicin and ifosfamide, but few studies have directly assessed whether doxorubicin should be administered alone or in combination with ifosfamide. EORTC trial 62012 assessed whether the addition of ifosfamide to doxorubicin improves survival of patients with advanced soft-tissue sarcoma compared with doxorubicin alone.

Doxorubicin alone or with ifosfamide for treating soft tissue sarcoma?