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New strategy to treat multiple sclerosis shows promise in mice - 0 views

  • Scientists
  • have identified a set of compounds that may be used to treat multiple sclerosis (MS) in a new way
  • existing MS therapies
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  • ppress the immune system
  • the compounds boost a population of progenitor cells that can in turn repair MS-damaged nerve fibers
  • cautioned that benztropine is a drug with dose-related adverse side effects, and has yet to be proven effective at a safe dose in human MS patients
  • the newly identified compounds, a Parkinson's disease drug called benztropine, was highly effective in treating a standard model of MS in mice, both alone and in combination with existing MS therapies
  • MS currently affects more than half a million people in North America and Europe, and more than two million worldwide
  • precise triggers are unknown, but certain infections and a lack of vitamin D are thought to be risk factors
  • In MS, immune cells known as T cells infiltrate the upper spinal cord and brain
  • causing inflammation and ultimately the loss of an insulating coating called myelin on some nerve fibers
  • As nerve fibers lose this myelin coating, they lose their ability to transmit signals efficiently, and in time may begin to degenerate
  • resulting symptoms, which commonly occur in a stop-start, "relapsing-remitting" pattern, may include limb weakness, numbness and tingling, fatigue, vision problems, slurred speech, memory difficulties and depression, among other problems
  • Current therapies
  • aim to suppress the immune attack that de-myelinates nerve fibers. But they are only partially effective and are apt to have significant adverse side effects
  • the new study
  • aimed at restoring a population of progenitor cells called oligodendrocytes
  • These cells normally keep the myelin sheaths of nerve fibers in good repair and in principle could fix these coatings after MS damages them
  • oligodendrocyte numbers decline sharply in MS, due to a still-mysterious problem with the stem-like precursor cells that produce them
  • team screened a library of about 100,000 diverse compounds for any that could potently induce OPCs to mature or "differentiate."
  • Several compounds scored well
  • benztropine, had been well characterized and indeed was already FDA-approved for treating Parkinson's disease
  • tests, benztropine showed a powerful ability to prevent autoimmune disease and also was effective in treating it after symptoms had arisen
  • virtually eliminating the disease's ability to relapse
  • benztropine on its own worked about as well as existing treatments, it also showed a remarkable ability to complement these existing treatments
  • two first-line immune-suppressant therapies, interferon-beta and fingolimod
  • Adding even a suboptimal level of benztropine
  • allowed
  • to cut the dose of fingolimod by 90%
  • the same disease-modifying effect as a normal dose
  • that dose-lowering could translate into a big reduction in
  • potentially serious side effects
  • researchers confirmed that benztropine works against disease in this mouse model by boosting the population of mature oligodendrocytes
  • in turn restore the myelin sheaths of damaged nerves
  • even as the immune attack continues
  • benztropine-treated mice showed no change in the usual signs of inflammation, yet their myelin was mostly intact, suggesting that it was probably being repaired as rapidly as it was being destroyed
  • Benztropine is known to have multiple specific effects on brain cells, including the blocking of activity at acetylcholine and histamine receptors and a boosting of activity at dopamine receptors
  • hope to learn more about how
  • its molecular structure might be optimized for this purpose
Mars Base

Hearing quality restored with bionic ear technology used for gene therapy - 0 views

  • Researchers
  • have for the first time used electrical pulses delivered from a cochlear implant to deliver gene therapy, thereby successfully regrowing auditory nerves
  • The research also heralds a possible new way of treating a range of neurological disorders, including Parkinson's disease, and psychiatric conditions such as depression through this novel way of delivering gene therapy.
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  • "People with cochlear implants do well with understanding speech, but their perception of pitch can be poor, so they often miss out on the joy of music," says UNSW Professor Gary Housley
  • The work centres on regenerating surviving nerves after age-related or environmental hearing loss, using existing cochlear technology
  • The cochlear implants are "surprisingly efficient" at localised gene therapy in the animal model, when a few electric pulses are administered during the implant procedure.
  • It has long been established that the auditory nerve endings regenerate if neurotrophins – a naturally occurring family of proteins crucial for the development, function and survival of neurons – are delivered to the auditory portion of the inner ear, the cochlea.
  • until now, research has stalled because safe, localised delivery of the neurotrophins can't be achieved using drug delivery, nor by viral-based gene therapy
  • developed a way of using electrical pulses delivered from the cochlear implant to deliver the DNA to the cells close to the array of implanted electrodes. These cells then produce neurotrophins.
  • the neurotrophin production dropped away after a couple of months
  • ultimately the changes in the hearing nerve may be maintained by the ongoing neural activity generated by the cochlear implant.
  • "We think it's possible that in the future this gene delivery would only add a few minutes to the implant procedure,"
  • Jeremy Pinyon, whose PhD is based on this work
  • "The surgeon who installs the device would inject the DNA solution into the cochlea and then fire electrical impulses to trigger the DNA transfer once the implant is inserted."
  • Integration of this technology into other 'bionic' devices such as electrode arrays used in deep brain stimulation
  • the treatment of Parkinson's disease and depression, for example) could also afford opportunities for safe, directed gene therapy of complex neurological disorders
  • implications far beyond hearing disorders
  • Professor Matthias Klugmann
  • "Gene therapy has been suggested as a treatment concept even for devastating neurological conditions and our technology provides a novel platform for safe and efficient gene transfer into tissues as delicate as the brain."
Mars Base

Scientists discover previously unknown cleaning system in brain - 0 views

  • A previously unrecognized system that drains waste from the brain at a rapid clip has been discovered by neuroscientists at the University of Rochester Medical Center
  • highly organized system acts like a series of pipes that piggyback on the brain's blood vessels, sort of a shadow plumbing system that seems to serve much the same function in the brain as the lymph system does in the rest of the body – to drain away waste products
  • hopeful that these findings have implications for many conditions that involve the brain, such as traumatic brain injury, Alzheimer's disease, stroke, and Parkinson's disease
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  • made the findings in mice, whose brains are remarkably similar to the human brain
  • Scientists have known that cerebrospinal fluid or CSF plays an important role cleansing brain tissue, carrying away waste products and carrying nutrients to brain tissue through a process known as diffusion
  • The newly discovered system circulates CSF to every corner of the brain much more efficiently, through what scientists call bulk flow or convection
  • It's as if the brain has two garbage haulers – a slow one that we've known about, and a fast one that we've just met
  • How has this system eluded the notice of scientists up to now
  • the system operates only when it's intact and operating in the living brain, making it very difficult to study
  • study the living, whole brain, the team used a technology known as two-photon microscopy, which allows scientists to look at the flow of blood, CSF and other substances in the brain of a living animal
  • If the glymphatic system fails to cleanse the brain as it is meant to, either as a consequence of normal aging, or in response to brain injury, waste may begin to accumulate in the brain. This may be what is happening with amyloid deposits in Alzheimer's disease
  • Perhaps increasing the activity of the glymphatic system might help prevent amyloid deposition from building up or could offer a new way to clean out buildups of the material in established Alzheimer's disease
  • took an in-depth look at amyloid beta
  • found that more than half the amyloid removed from the brain of a mouse under normal conditions is removed via the glymphatic system
Mars Base

New drug could treat Alzheimer's, multiple sclerosis and brain injury - 0 views

  • A new class of drug
  • shows early promise of being a one-size-fits-all therapy for Alzheimer's disease, Parkinson's disease, multiple sclerosis and traumatic brain injury by reducing inflammation in the brain
  • The drugs
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  • target a particular type of brain inflammation
  • brain inflammation, also called neuroinflammation, is increasingly believed to play a major role in the progressive damage characteristic of these chronic diseases and brain injuries.
  • offers an entirely different therapeutic approach to Alzheimer's than current ones being tested to prevent the development of beta amyloid plaques in the brain
  • The plaques are an indicator of the disease but not a proven cause
  • given to a mouse genetically engineered to develop Alzheimer's, it prevents the development of the full-blown disease
  • identifies the optimal therapeutic time window for administering the drug, which is taken orally and easily crosses the blood-brain barrier.
  • In previous animal studies, the same drug reduced the neurological damage caused by closed-head traumatic brain injury and inhibited the development of a multiple sclerosis-like disease. In these diseases as well as in Alzheimer's, the studies show the therapy time window is critical
  • work by preventing the damaging overproduction of brain proteins called proinflammatory cytokines
  • Scientists now believe overproduction of these proteins contributes to the development of many degenerative neurological diseases
  • When too many of the cytokines are produced, the synapses of the brain begin to misfire
  • mouse model of Alzheimer's received MW151 three times a week starting at six months of age, right at the time the proinflammatory cytokines began to rise. This would be the comparable stage when a human patient would begin to experience mild cognitive impairment
  • drug protected against the damage associated with learning and memory impairment
  • before Alzheimer's memory changes are at a late stage may be a promising future approach to therapy
  • In M.S., overproduction of the proinflammatory cytokines damage the central nervous system and the brain
  • proteins directly or indirectly destroy the insulation or coverings of the nerve cells that transmit signals down the spinal cord
  • insulation is stripped, messages aren't properly conducted down the spinal cord
  • When mice that were induced to develop an M.S.-like disease received MW151 orally, they did not develop disease as severe.
  • After a traumatic brain injury, the glia cells in the brain become hyperactive and release a continuous cascade of proinflammatory cytokines
  • As a result of this hyperactivity, researchers believe the brain is more susceptible to serious damage following a second neurological injury.
  • when MW151 is given during an early therapeutic window three to six hours after the injury, it blocks glial activation and prevents the flood of proinflammatory cytokines after a traumatic brain injury
  • early on after traumatic brain injury or a even a stroke, you could possibly prevent the long-term complications of that injury including the risk of seizures, cognitive impairment and, perhaps, mental health issues
  • Stroke also causes inflammation in the brain that may also be linked to long-term complications including epilepsy and cognitive deficits
Mars Base

Personalized medicine closer to reality: Study uses stem cells to study variants of Par... - 0 views

  • A nationwide consortium of scientists at 20 institutions, led by a principal faculty member at the Harvard Stem Cell Institute (HSCI), has used stem cells to take a major step toward developing personalized medicine to treat Parkinson’s disease
  • scientists created induced pluripotent stem cells (iPS cells) from the skin cells of patients and at-risk individuals carrying genetic mutations implicated in Parkinson’s disease
  • used those cells to derive neural cells
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  • researchers report that although approximately 15 genetic mutations are linked to forms of Parkinson
  • researchers determined that certain compounds or drugs could reverse some signs of disease in the cultured cells with specific genetic mutations
  • suggest new opportunities for clinical trials of Parkinson’s disease, wherein cell reprogramming technology could be used to identify the patients most likely to respond to a particular intervention
  • this study points the way to screening patients with Parkinson’s for their particular variation of the disease
  • drugs shown effective to work on that variation
Mars Base

Researchers identify brain cells responsible for keeping us awake - 0 views

  • Bright light makes it easier to stay awake
  • Very bright light not only arouses us but is known to have antidepressant effects.
  • Bright light makes it easier to stay awake.
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  • dark rooms can make us sleepy.
  • researchers at UCLA have identified the group of neurons that mediates whether light arouses us — or not
  • the cells necessary for a light-induced arousal response are located in the hypothalamus
  • an area at the base of the brain responsible for, among other things, control of the autonomic nervous system, body temperature, hunger, thirst, fatigue — and sleep.
  • the activity of hypocretin neurons in their WT littermates was maximized when working for positive rewards during the light phase, but the cells were not activated when performing the same tasks in the dark phase.
  • This same UCLA research group earlier determined that the loss of hypocretin was responsible for narcolepsy and the sleepiness associated with Parkinson's disease
  • This current finding explains prior work in humans that found that narcoleptics lack the arousing response to light, unlike other equally sleepy individuals
  • researchers examined the behavioral capabilities of mice that had their hypocretin genetically "knocked-out" (KO mice) and compared them with the activities of normal, wild-type mice (WT) that still had their hypocretin neurons
  • they found that the KO mice were only deficient at working for positive rewards during the light phase
  • During the dark phase, however, these mice learned at the same rate as their WT littermates and were completely unimpaired in working for the same rewards
  • These cells release a neurotransmitter called hypocretin
  • findings suggest that administering hypocretin and boosting the function of hypocretin cells will increase the light-induced arousal response
  • Conversely, blocking their function by administering hypocretin receptor blockers will reduce this response and thereby induce sleep
  • implications for treating sleep disorders as well as depression
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