Posts tagged treatment

Washington State University researchers have developed a new drug candidate that dramatically improves the cognitive function of rats with Alzheimer’s-like mental impairment.

Their compound, which is intended to repair brain damage that has already occurred, is a significant departure from current Alzheimer’s treatments, which either slow the process of cell death or inhibit cholinesterase, an enzyme believed to break down a key neurotransmitter involved in learning and memory development.

Such drugs, says Joe Harding, a professor in WSU’s College of Veterinary Medicine, are not designed to restore lost brain function, which can be done by rebuilding connections between nerve cells.

"This is about recovering function,” he says. "That’s what makes these things totally unique. They’re not designed necessarily to stop anything. They’re designed to fix what’s broken. As far as we can see, they work.”

Harding, College of Arts and Sciences Professor Jay Wright and other WSU colleagues report their findings in the online “Fast Forward” section of the Journal of Pharmacology and Experimental Therapeutics.

(Source: news.wsu.edu)

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Three studies conducted as part of Wayne State University’s Systems Biology of Epilepsy Project (SBEP) could result in new types of treatment for the disease and, as a bonus, for behavioral disorders as well.

The SBEP started out with funds from the President’s Research Enhancement Fund and spanned neurology, neuroscience, genetics and computational biology. It since has been supported by multiple National Institutes of Health-funded grants aimed at identifying the underlying causes of epilepsy, and it is uniquely integrated within the Comprehensive Epilepsy Program at the Wayne State School of Medicine and the Detroit Medical Center.

Under the guidance of Jeffrey Loeb, M.D., Ph.D., associate director of the Center for Molecular Medicine and Genetics (CMMG) and professor of neurology, the project brings together researchers from different fields to create an interdisciplinary research program that targets the complex disease. The multifaceted program at Wayne State is like no other in the world, officials say, with two primary goals: improving clinical care and creating novel strategies for diagnosis and treatment of patients with epilepsy.

(Source: research.wayne.edu)

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Most people know the frustration of having a word on the “tip of your tongue” that they simply can’t remember. But that passing nuisance can be an everyday occurrence for someone with aphasia, a communication disorder caused by a stroke or other brain damage that impairs the ability to process language.

About 1 million Americans — roughly one in every 250 — are affected by aphasia, which can also impact reading and writing skills. But how they acquire the problem and how long they’ll endure it differ from person to person, explained Ellayne Ganzfried, a speech-language pathologist and executive director of the National Aphasia Association.

"No two people with aphasia are alike because everyone’s brain responds to the injury in a different way," Ganzfried said. "About half of people who have aphasia recover quickly, within the first few days. If the symptoms of aphasia last longer than two or three months, a complete recovery is unlikely … [though] some people continue to improve over a period of years and even decades."

Strokes are the most common cause, followed by head injuries, tumors, migraines or other neurological issues. Depending on the damage to the brain regions controlling language, which are typically in the left hemisphere, the resulting aphasia can be broken into four broad categories:

• Difficulty expressing thoughts through speech or writing
• Difficulty understanding spoken or written language
• Difficulty using the correct names for objects, people, places or events
• Loss of almost all language function, with no ability to speak or understand speech.

"Processing language requires the collaboration of lots of different parts or systems of the brain," explained Karen Riedel, director of speech-language pathology at the Rusk Institute of Rehabilitation Medicine at NYU Langone Medical Center in New York City. "The whole brain ‘talks’ — the whole brain has something to do with the use of language."

Because of this, a variety of therapies are used to help people regain as much speech and language as possible. But regardless of the injury, people with aphasia have the best chances for recovery when language therapy begins immediately, Riedel said.

Because aphasia is so variable, a therapy that helps one person might not help another, she noted. Tried-and-true techniques include melodic intonation therapy, which uses melody and rhythm to help improve the ability to retrieve words, and constraint-induced therapy, which forces people to use speech over other communication methods.

But technology, Riedel said, has introduced new language-improvement techniques into the mix over the last few years that are both exciting and fun. Several apps available for iPhone or iPad involve synthetic speech that helps engage those with aphasia in yet another realm of communication.

"Our patients have much more access to different kinds of programs that are computer-based," she said. "There’s always something new around the corner."

What remains a constant concern, however, is the misunderstanding many people have of those with language difficulties and how to treat them, Ganzfried and Riedel agreed.

"Many people with aphasia will become socially isolated because of their communication difficulties, which can lead to depression," Ganzfried said. "There are also many misconceptions about aphasia, including that the person is mentally unstable or under the influence of drugs or alcohol. It’s also extremely frustrating. Imagine knowing what you want to say in your head but you can’t get the words out."

(Source: consumer.healthday.com)

Brain metastases are common secondary complications of other types of cancer, particularly lung, breast and skin cancer. The body’s own immune response in the brain is rendered powerless in the fight against these metastases by inflammatory reactions. Researchers at the MedUni Vienna have now, for the first time, precisely characterised the brain’s immune response to infiltrating metastases. This could pave the way to the development of new, less aggressive treatment options.

“The active phagocytes are quite literally overwhelmed by the tumour and even the white blood cells are too weak to fight off these metastases on their own; they have to be stimulated before they can have any effect,” explains oncologist Matthias Preusser from the University Department of Internal Medicine I and the Comprehensive Cancer Center (CCC), a joint institution operated by the MedUni Vienna and the Vienna General Hospital.

Brain tissue was obtained for investigation from autopsies carried out on people who had metastatic disease secondary to breast, lung or skin cancer. These are also the most common types of primary tumour. Brain metastases develop because they spread from the tumours into other parts of the body right up to the brain.

The scientists at the Clinical Institute of Neurology, the Centre for Brain Research, the CCC and the University Department of Internal Medicine I have discovered that metastases in the brain do encounter a wall of phagocytes, but it is too weak to successfully arrest the tumour’s development. To do this, white blood cells (lymphocytes) need to be mobilised in greater numbers as the second instance of the immune defence system.

These findings could lead to new therapeutic strategies being developed that will aim to increase the activation of white blood cells or other parts of the immune system – perhaps through medication such as antibody treatments or vaccines.

300 to 400 patients with brain metastases are treated each year at the MedUni Vienna. The standard treatment in most cases is radiotherapy to the head or generalised irradiation of the brain – which is associated with certain risks and possible side effects. Only in very few cases are drug-based treatment methods available for certain types of cancer. Says Preusser: “Our findings could represent an important step towards the development of less aggressive forms of treatment.”

(Source: meduniwien.ac.at)

A new oral medication to treat patients in the early stages of multiple sclerosis has shown considerable promise in two clinical trials, researchers announced on Wednesday.

The medication is on track to become just the third oral drug available to M.S. patients, and potentially the safest and most effective, experts said. The second oral drug, called Aubagio, was approved just last week.

M.S. was virtually untreatable only two decades ago, but today nine “disease modifying” drugs are available for early-stage patients; a half-dozen more are in the late stages of development. Most patients in the early stage of the disease, a form called relapsing-remitting M.S., take drugs by injection.

The two new studies, published online in The New England Journal of Medicine, found that the drug BG-12, developed by Biogen Idec, reduced relapse rates in patients with relapsing M.S. by about 50 percent. The drug also significantly reduced the frequency of new brain lesions often associated with these attacks, and slowed the progression of disease compared with a placebo.

The studies were Phase 3 trials, a last step on the road to drug approval. The Food and Drug Administration is required to make a decision about the drug’s approval before the end of this year.

“This drug is clearly quite effective in managing disease and reducing disability, and the safety profile looks quite good,” said Timothy Coetzee, the chief research officer at the National Multiple Sclerosis Society, who was not involved in the studies.

Multiple sclerosis is often a progressive disease in which the immune system damages neurons in the brain and spinal cord. A majority of people with M.S. have relapsing-remitting M.S., characterized by flare-ups that cause lesions in the brain to develop and neurological symptoms to emerge or worsen. Eventually, more than half of patients develop a progressive form of M.S., leading to permanent disabilities.

Interferons, the drugs most commonly used in relapsing M.S., reduce relapses by about 30 percent, and have not been shown to slow the progression of the disease and disability. The newly approved Aubagio also reduces relapses by about 30 percent, and it has the advantage of being an oral drug.

Two drugs that are substantially more effective, Tysabri and Gilenya, come with serious risks including, in rare cases, death. They are used as second-line treatments when an initial approach fails, and patients require some monitoring.

In the new studies, called Define and Confirm, patients were randomized into two groups, taking 240 milligrams of BG-12 either twice or three times a day. Patients in a third group took a placebo. The combined results showed that the drug reduced the relapse rate by about 50 percent. There was minimal difference between the twice-daily and thrice-daily regimens.

Taking BG-12 twice a day reduced the number of new or newly enlarging brain lesions by 71 percent to 99 percent, depending on the type of lesion and the study. The Define study found a statistically significant 38 percent reduction in the progression to disability.

The most frequent side effects were a temporary flushing and warm feeling and gastrointestinal symptoms including nausea, diarrhea, cramping and vomiting. Though both types of side effects were common, they tended to diminish after the first few weeks of use and were tolerated by most patients.

BG-12 is an anti-inflammatory that works by protecting nerves against injury. It is a fumaric acid, very similar to one widely used in Germany for the treatment of psoriasis. “The safety track record is well known and appears to be very strong,” said Dr. Robert Fox, lead author of one of the two new studies and medical director of the Mellen Center for Multiple Sclerosis Treatment and Research at the Cleveland Clinic.

“It’s a bright day for M.S. patients, but there is a gray cloud in that we still don’t have anything for those with progressive M.S.,” he added.

August 21, 2012 by Kathleen Raven

Stem cell treatment could lower inflammation levels and demonstrate whether autism is an autoimmune disease

Image: Nature News

Families with autistic children must navigate a condition where questions outnumber the answers, and therapies remain sparse and largely ineffective. A clinical trial being conducted by the Sutter Neuroscience Institute in Sacramento, California to address this situation began recruiting participants today for a highly experimental stem cell therapy for autism. The institute plans to find 30 autistic children between ages 2 and 7 with cord blood banked at the privately-run Cord Blood Registry, located about 100 miles west of the institute. Already one other clinical trial, with 37 total participants between ages 3 and 12 years old, has been completed in China. The researchers affiliated with Beike Biotechnology in Shenzhen, the firm that sponsored the study, have not yet published any papers from that the trial, which used stem cells from donated cord blood. Mexican researchers are currently recruiting kids for yet another type of autism stem cell trial that will harvest cells from the participant’s fat tissue.

But for each of these officially registered trials, many more undocumented stem cell therapy treatments take place for clients who are willing to pay enough. “Our research is important because many people are going to foreign countries and spending a lot of money on therapy that may not be valid,” says Michael Chez, a pediatric neurologist and lead investigator of the study at Sutter.

A major difference between the Sutter trial and those in China is that his will use the child’s own stem cells, rather than those from a donor. Chez hypothesizes that one way autologous stem cell infusion might work is by reducing inflammation within the body’s immune system. This would answer previous research that suggests that autism may be an autoimmune disease. “One of our exploratory goals will be to look at inflammatory markers in cells,” he says.

The study’s primary goal, however, will be assessing changes in patients’ speaking and understanding of vocabulary. For each individual, researchers will create a baseline benchmark that establishes current skill levels. The group will be evenly divided, with one initially receiving an infusion of their own, unmodified cord blood stem cells and the other a placebo treatment of saline injection. Six months later, all of the children will be tested on their ability to comprehend and form words. The groups will then be switched. In the course of the 13-month-long study, both groups will receive only one stem cell therapy infusion.

Not all stem cell scientists who study neurodevelopmental diseases are ready to invest great hope that the autism stem cell trial will succeed. “I wish I could tell you I’m optimistic about the end results,” says James Carroll, a pediatric neurologist at the Georgia Health Sciences University in Augusta who began a clinical trial two years ago to better understand how stem cell therapy affects patients with cerebral palsy. “But so far we have not seen any kind of miraculous recovery in our cerebral palsy patients. I would be delighted if that changes.”

Members in the stem cell therapy patient community think Chez will have no shortage of volunteers for the trial. Jeremy Lowey, who lives in Sacramento and has struggled with a rare condition known as non-verbal learning disorder, arranged for his own stem cell therapy treatment in India last year, which he called life-changing. He receives numerous Facebook requests from parents of autistic children who are curious to know more. He always begins his conversations by saying, “Go slowly and think hard about your decision.”

Source: Scientific American

ScienceDaily (Aug. 16, 2012) — In multiple sclerosis, the immune system attacks nerves in the brain and spinal cord, causing movement problems, muscle weakness and loss of vision. Immune cells called dendritic cells, which were previously thought to contribute to the onset and development of multiple sclerosis, actually protect against the disease in a mouse model, according to a study published by Cell Press in the August issue of the journal Immunity. These new insights change our fundamental understanding of the origins of multiple sclerosis and could lead to the development of more effective treatments for the disease.

"By transfusing dendritic cells into the blood, it may be possible to reduce autoimmunity," says senior study author Ari Waisman of University Medical Center of Johannes Gutenberg University Mainz. "Beyond multiple sclerosis, I can easily imagine that this approach could be applied to other autoimmune diseases, such as inflammatory bowel disease and psoriasis."

In an animal model of multiple sclerosis known as experimental autoimmune encephalomyelitis (EAE), immune cells called T cells trigger the disease after being activated by other immune cells called antigen-presenting cells (APCs). Dendritic cells are APCs capable of activating T cells, but it was not known whether dendritic cells are the APCs that induce EAE.

In the new study, Waisman and his team used genetic methods to deplete dendritic cells in mice. Unexpectedly, these mice were still susceptible to EAE and developed worse autoimmune responses and disease clinical scores, suggesting that dendritic cells are not required to induce EAE and other APCs stimulate T cells to trigger the disease. The researchers also found that dendritic cells reduce the responsiveness of T cells and lower susceptibility to EAE by increasing the expression of PD-1 receptors on T cells.

"Removing dendritic cells tips the balance toward T cell-mediated autoimmunity," says study author Nir Yogev of University Medical Center of Johannes Gutenberg University Mainz. "Our findings suggest that dendritic cells keep immunity under check, so transferring dendritic cells to patients with multiple sclerosis could cure defects in T cells and serve as an effective intervention for the disease."

Source: Science Daily