Posts tagged therapy
Posts tagged therapy
An investigational treatment for an inherited form of Lou Gehrig’s disease has passed an early phase clinical trial for safety, researchers at Washington University School of Medicine in St. Louis and Massachusetts General Hospital report.
The researchers have shown that the therapy produced no serious side effects in patients with the disease, also known as amyotrophic lateral sclerosis (ALS). The phase 1 trial’s results, available online in Lancet Neurology, also demonstrate that the drug was successfully introduced into the central nervous system.
The treatment uses a technique that shuts off the mutated gene that causes the disease. This approach had never been tested against a condition that damages nerve cells in the brain and spinal cord.
“These results let us move forward in the development of this treatment and also suggest that it’s time to think about applying this same approach to other mutated genes that cause central nervous system disorders,” says lead author Timothy Miller, MD, PhD, assistant professor of neurology at Washington University. “These could include some forms of Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and other conditions.”
ALS destroys nerves that control muscles, gradually leading to paralysis and death. For treatment of the disease, the sole FDA-approved medication, Riluzole, has only a marginal effect.
Most cases of ALS are sporadic, but about 10 percent are linked to inherited mutations. Scientists have identified changes in 10 genes that can cause ALS and are still looking for others.
The study focused on a form of ALS caused by mutations in a gene called SOD1, which account for 2 percent of all ALS cases. Researchers have found more than 100 mutations in the SOD1 gene that cause ALS.
“At the molecular level, these mutations affect the properties of the SOD1 protein in a variety of ways, but they all lead to ALS,” says Miller, who is director of the Christopher Wells Hobler Lab for ALS Research at the Hope Center for Neurological Disorders at Washington University.
Rather than try to understand how each mutation causes ALS, Miller and his colleagues focused on blocking production of the SOD1 protein using a technique called antisense therapy.
To make a protein, cells have to copy the protein-building instructions from the gene. Antisense therapy blocks the cell from using these copies, allowing researchers to selectively silence individual genes.
“Antisense therapy has been considered and tested for a variety of disorders over the past several decades,” Miller says. “For example, the FDA recently approved an antisense therapy called Kynamro for familial hypercholesterolemia, an inherited condition that increases cholesterol levels in the blood.”
Miller and colleagues at the University of California-San Diego devised an antisense drug for SOD1 and successfully tested it in an animal model of the disease.
Merit Cudkowicz, MD, chief of neurology at Massachusetts General Hospital, was co-PI of the phase I clinical safety trial described in the new paper. Clinicians at Barnes-Jewish Hospital, Massachusetts General Hospital, Johns Hopkins Hospital and the Methodist Neurological Institute in Houston gave antisense therapy or a placebo to 21 patients with SOD1-related ALS. Treatment consisted of spinal infusions that lasted 11 hours.
The scientists found no significant difference between side effects in the control and treatment groups. Headache and back pain, both of which are often associated with spinal infusion, were among the most common side effects.
Immediately after the injections, the researchers took spinal fluid samples. This let them confirm the antisense drug was circulating in the spinal fluid of patients who received the treatment.
To treat SOD1-related ALS in the upcoming phase II trial, researchers will need to increase the dosage of the antisense drug. As the dose rises, they will watch to ensure that the therapy does not cause harmful inflammation or other side effects as it lowers SOD1 protein levels.
“All the information that we have so far suggests lowering SOD1 will be safe,” Miller says. “In fact, completely disabling SOD1 in mice seems to have little to no effect. We think it will be OK in patients, but we won’t know for sure until we’ve conducted further trials.”
The therapy may one day be helpful in the more common, noninherited forms of ALS, some of which may be linked to problems with the SOD1 protein.
“Before we can consider using this same therapy for sporadic ALS, we need more evidence that SOD1 is a major contributor to these forms of the disorder,” Miller says.
The trial was conducted with support from ISIS Pharmaceuticals, which co-owns a patent on the SOD1 antisense drug.
Dolphin-assisted therapy for children with mental disabilities has made a splash in the West, and China is now riding the experimental tide. Shi Yingying and Erik Nilsson examine the impact these marine mammals have on the children they come into contact with.
Zheng Jun says 15 sessions with a pair of bottle-nosed dolphins at Hangzhou Polar Ocean Park have helped his 5-year-old autistic son become “aware” and “alert” enough to become his kindergarten’s class monitor. The father believes the dolphin-assisted therapy has been more effective than any other treatment. “Now, you can’t tell he’s different from his classmates,” he says. Zheng became a believer after he visited an Australian dolphin-swim program years ago. He says his son is elated when he splashes with the creatures in the park in Zhejiang province’s capital.
More than 80 parents of children with severe mental disabilities have booked all of next year’s spots in the program (sessions only run in the summer because the water temperatures are too cold for the kids in other seasons).
So, newcomers must wait until 2014, says Liu Quansheng, manager of the park’s owner, Zhejiang Aquarium Investment Group. Despite the demand, dolphin-assisted therapy has not been scientifically proven. Still, many experts and parents of special-needs children swear by it.
Lithium is a ‘gold standard’ drug for treating bipolar disorder, however not everyone responds in the same way. New research published in BioMed Central’s open access journal Biology of Mood & Anxiety Disorders finds that this is true at the levels of gene activation, especially in the activation or repression of genes which alter the level the apoptosis (programmed cell death). Most notably BCL2, known to be important for the therapeutic effects of lithium, did not increase in non-responders. This can be tested in the blood of patients within four weeks of treatment.
A research team from Yale University School of Medicine measured the changing levels of gene activity in the blood of twenty depressed adult subjects with bipolar disorder before treatment, and then fortnightly once treatment with lithium carbonate had begun.
Over the eight weeks of treatment there were definite differences in the levels of gene expression between those who responded to lithium (measured using the Hamilton Depression Rating Scale) and those who failed to respond. Dr Robert Beech who led this study explained, “We found 127 genes that had different patterns of activity (turned up or down) and the most affected cellular signalling pathway was that controlled programmed cell death (apoptosis).”
For people who responded to lithium the genes which protect against apoptosis, including Bcl2 and IRS2, were up regulated, while those which promote apoptosis were down regulated, including BAD and BAK1.
The protein coded by BAK1 can open an anion channel in mitochondrial walls which leads to leakage of mitochondrial contents and activation of cell death pathways. Damage similar to this has been seen within the prefrontal cortex of the brain of patients with bipolar disorder. BAD protein is thought to promote BAK1 activity, while Bcl2 binds to BAK1 and prevents its ability to bind to the channel.
Dr Beech continued, “This positive swing in regulation of apoptosis for lithium responders was measurable as early as four weeks after the start of treatment, while in non-responders there was a measureable shift in the opposite direction. It seems then, that increased expression of BCL2 and related genes is necessary for the therapeutic effects of lithium. Understanding these differences in genes expression may lead towards personalized treatment for bipolar disorder in the future.”
A fine-tuned combination of two existing pharmaceutical drugs has shown promise as a potential new therapy for people addicted to cocaine—a therapy that would reduce their craving for the drug and blunt their symptoms of withdrawal.
In laboratory experiments at The Scripps Research Institute, the potential therapy, which combines low doses of the drug naltrexone with the drug buprenorphine, made laboratory rats less likely to take cocaine compulsively—a standard preclinical test that generally comes before human trials.
While the two-drug combination would have to prove safe and effective for people in clinical trials before approval by the U.S. Food and Drug Administration (FDA), the work represents a significant advance in the field because there are currently no FDA-approved medications for treating cocaine addiction.
August 2, 2012
New tools have confirmed high rates of misdiagnosis of patients with chronic disorders of consciousness, such as the vegetative state. An increasing number of patients’ families wish to use these novel techniques for diagnosis, prognosis, and treatment. An international team of researchers, including Dr. Éric Racine, researcher at the IRCM, analyzed the clinical, social and ethical issues that clinicians are now facing. Their article is published in the August edition of The Lancet Neurology, a renowned journal in the field of clinical neurology.
“Patients with disorders of consciousness have traditionally been regarded as unaware by definition, but findings from recent clinical studies have revealed astounding cases of awareness despite clinical unresponsiveness,” explains Dr. Racine, a Montréal neuroethics specialist.
Severe brain injury can leave patients with chronic disorders of consciousness, which are medical conditions that inhibit consciousness. Patients thus have severe motor and cognitive impairments, remain fully dependent on others for all activities of daily living, and have no or very limited means to functionally communicate their thoughts or wishes, depending on their state.
Even with a careful neurological assessment of these types of disorders, some signs of awareness can elude the clinician because the clinical diagnosis relies on the observation of motor signs of awareness, which can be very subtle and fluctuate over time.
New technological developments can now measure brain function both in resting states and in response to simple commands, independent of muscle function, which could help establish a more accurate diagnosis. As a result, diagnostic classifications have been revised and prognostic knowledge is improving. For the first time, therapeutic studies have recently shown the effects of treatment on the improvement of patient responsiveness.
“The medical decision to stop or continue rehabilitation, or to transfer a patient to a long-term care facility can be hard to accept for the family, but one of the most difficult treatment decisions by family members remains whether to continue life-sustaining therapy or to discontinue it and only provide palliative care,” says Dr. Racine.
Media coverage of disorders of consciousness has increased and information on the subject is increasingly available to the public. Clinicians such as neurologists, rehabilitation specialists, family doctors, and nurses must answer more requests from patients’ family members for novel diagnostic and therapeutic procedures.
“Clinicians therefore need to be prepared to discuss disorders of consciousness with ethical sensitivity, especially considering that the new procedures remain investigational,” adds Dr. Racine. “They must be aware of the level of evidence supporting them and of the unavoidable ethical and social issues involved in responding to requests from patients’ family members.”
Provided by Institut de recherches cliniques de Montreal
July 30, 2012
In the first human study of its kind, researchers found that using stem cells to re-grow craniofacial tissues—mainly bone—proved quicker, more effective and less invasive than traditional bone regeneration treatments.
Researchers from the University of Michigan School of Dentistry and the Michigan Center for Oral Health Research partnered with Ann Arbor-based Aastrom Biosciences Inc. in the clinical trial, which involved 24 patients who required jawbone reconstruction after tooth removal.
Patients either received experimental tissue repair cells or traditional guided bone regeneration therapy. The tissue repair cells, called ixmyelocel-T, are under development at Aastrom, which is a U-M spinout company.
“In patients with jawbone deficiencies who also have missing teeth, it is very difficult to replace the missing teeth so that they look and function naturally,” said Darnell Kaigler, principal investigator and assistant professor at the U-M School of Dentistry. “This technology and approach could potentially be used to restore areas of bone loss so that missing teeth can be replaced with dental implants.”
William Giannobile, director of the Michigan Center for Oral Health Research and chair of the U-M Department of Periodontics and Oral Medicine, is co-principal investigator on the project.
The treatment is best suited for large defects such as those resulting from trauma, diseases or birth defects, Kaigler said. These defects are very complex because they involve several different tissue types—bone, skin, gum tissue—and are very challenging to treat.
The main advantage to the stem cell therapy is that it uses the patient’s own cells to regenerate tissues, rather than introducing man-made, foreign materials, Kaigler said.
The results were promising. At six and 12 weeks following the experimental cell therapy treatment, patients in the study received dental implants. Patients who received tissue repair cells had greater bone density and quicker bone repair than those who received traditional guided bone regeneration therapy.
In addition, the experimental group needed less secondary bone grafting when getting their implants.
The cells used for the therapy were originally extracted from bone marrow taken from the patient’s hip. The bone marrow was processed using Aastrom’s proprietary system, which allows many different cells to grow, including stem cells. These stem cells were then placed in different areas of the mouth and jaw.
Stem cell therapies are still probably 5-10 years away from being used regularly to treat oral and facial injuries and defects, Kaigler said. The next step is to perform more clinical trials that involve larger craniofacial defects in a larger number of patients.
The study, “Stem cell therapy for craniofacial bone repair: A randomized, controlled clinical trial,” appears this month in the journal Cell Transplantation.
See the video here
Source: University of Michigan
Dr. Penelope McNulty, a neurophysiologist at Neuroscience Research Australia, will present new data that shows the Wii is an effective rehabilitation tool at an international conference of the Society of Electrophysiology and Kinesiology in Brisbane on 20 July.
Dr. McNulty’s data shows that an intensive, two-week training program based on the Wii can result in significant improvements in the way stroke patients are able to use their limbs, even for people that had a stroke many years ago.
“It was previously thought that the movement and function stroke patients had at the time they left hospital was the only recovery they would make,” says Dr. McNulty.
“But we have worked with people who have had strokes one month to 21 years ago, and excitingly, they all improve,” she added.
There are over 60,000 strokes in Australia each year and there is a crucial need to improve rehabilitation methods because this is the only method known to restore movement in stroke-affected limbs.
“The Wii is inexpensive, easy to use and, very importantly, fun. This type of rehabilitation motivates participants to actually complete their therapy, which is essential for maximum recovery,” Dr. McNulty says.
“Everyone notices improvements not just using the Wii, but in activities they do every day, such as opening a door or using a fork,” Dr. McNulty concluded.