GAINESVILLE, Fla. — Sparking production of a hormone in the brain that people with epilepsy often lack could prevent debilitating seizures, University of Florida researchers have discovered.
The researchers used gene therapy in rats to stimulate production of somatostatin, a seizure-stopping chemical that naturally occurs in the brain. The study was published in the February issue of the journal Neuroscience Letters.
The choice of somatostatin was not random. A connection between somatostatin and epilepsy was already suspected.
People with epilepsy tend to have lower levels of the hormone somatostatin, as do people with Alzheimer’s disease. Although somatostatin, which belongs to a group of protein-like molecules called neuropeptides, is present in the brains of people with epilepsy, scientists have shown that its levels decrease during seizures, said Rabia Zafar, the lead author of the paper and a former postdoctoral associate in Carney’s lab.
There's still the issue of safety. Development of safe and effective gene therapy delivery delivery mechanisms for brain cells raise prospects for a wide range of benefits. Imagine altering gene expression levels in the chronically depressed for example. Or raise expression of genes associated with higher IQ once the genetic variants that control intelligence are identified. Also, gene therapies will eventually be used to do repair of aging brains.
At the same time, powerful ways to permanently alter brain metabolism raise worrisome prospects as well. Imagine lying asleep in a hotel on a business trip, a gas gets released into your hotel room to keep you asleep and then agents for a foreign government inject you with a gene therapy that makes you more risk or less risk averse, more depressed, more pliable, or otherwise altered in ways that gave your competitors an advantage. Will people some day secretly deliver gene therapies to alter the personalities of their lovers or subordinates or bosses? A brain malleable to gene therapy is a brain that can be made to work against its interests.
New Scientist reports from the latest Strategies for Engineered Negligible Senescence (SENS - all about reversing the aging process) conference in Cambridge UK and reveals some scientists find they can deliver stem cells into mouse brains with nose drops.
Since proteins, bacteria and viruses can enter the brain this way, Lusine Danielyan at the University Hospital of Tübingen in Germany, and her colleagues, wondered if stem cells would also migrate into the brain through the cribriform plate.
To test their idea, they dripped a suspension of fluorescently labelled stem cells into the noses of mice. The mice snorted them high into their noses, and the cells migrated through the cribriform plate. Then they travelled either into the olfactory bulb - the part of the brain that detects and deciphers odours - or into the cerebrospinal fluid lining the skull, migrating across the brain. The stem cells then moved deeper into the brain.
Now all we need are stem cells suitably programmed to, for example, replace aged neurons, aged glial cells, and even aged cells in brain arteries and veins. Then snort up.
Improvements in methods to create induced pluripotent stem cells (most recently at Stanford using fat cells) create the prospect of stem cells created from one's own body. No need to worry about immune rejection. We probably still need further improvements that reduce risk that the stem cells will turn cancerous. Then we need improvements in methods to turn pluripotent stem cells into whatever stem cell types we most want to send in the brain.
Okay, suppose we jump ahead 10 or 20 years and those problems are solved. Time to snort stem cells to improve our brains. That'll help aging brains. But where it gets really interesting is when we discover which genetic variations contribute to higher intelligence. Can stem cells genetically engineered for high IQ genes boost our intelligence? If so, snorting stem cells could make a whole society smarter. In 20 years will that become possible?
Speed up training of the motor control area of the brain with mild electric shocks applied via surface electrodes. No, I am not recommending that anyone actually do this.
People who received a mild electrical current to a motor control area of the brain were significantly better able to learn and perform a complex motor task than those in control groups. The findings could hold promise for enhancing rehabilitation for people with traumatic brain injury, stroke and other conditions.
The study is presented in the January 20, 2009 early online edition of the Proceedings of the National Academy of Sciences, and was conducted by researchers at the National Institutes of Health (NIH). The research team from NIH's National Institute of Neurological Disorders and Stroke (NINDS) worked in collaboration with investigators at Columbia University in New York City and Johns Hopkins University in Baltimore.
But this technique does lend itself to all sorts of ways to describe it. "Our teacher is absolutely electrifying" or "I was shocked by what I learned in school today" or "The work-out made me feel tingly all over". Can you come up with something more jolting?
You can imagine kids wanting to use this technique to master a video game more rapidly.
Subjects in this study were presented with a novel and challenging motor task, which involved squeezing a "joy stick" to play a targeting game on a computer monitor, which they practiced over five consecutive days. During practice, one group received 20 minutes of transcranial direct current stimulation (tDCS) and the other group received only a 30 second "sham" stimulation. tDCS involves mild electrical stimulation applied through surface electrodes on the head, and works by modulating the excitability, or activity, of cells in the brain's outermost layers. In this study, Dr. Cohen and his team directed tDCS to the primary motor cortex, the part of the brain that controls movement.
Over the five-day training period, the skill of the tDCS group improved significantly more than that of the control (sham) group, apparently through an effect on consolidation. During the three month follow-up period, the two groups forgot the skill at about the same rate, but the tDCS group continued to perform better because they had learned the skill better by the end of training.
The game was very stimulating.
For those who suffer with the debilitating symptoms of Parkinson's disease, Deep Brain Stimulation offers relief from the tremors and rigidity that can't be controlled by medicine. A particularly troublesome downside, though, is that these patients often exhibit compulsive behaviors that healthy people, and even those taking medication for Parkinson's, can easily manage.
Michael Frank, an assistant professor of psychology and director of the Laboratory for Neural Computation and Cognition at The University of Arizona, and his research colleagues have shed some light on how DBS interferes with the brain's innate ability to deliberate on complicated decisions. Their results are published in the current (Oct. 26) issue of the journal Science.
A recent episode of The Bionic Woman featured people operating under orders from neural implants controlled by terrorists. These Parkinson's patients are behaving differently due to implants. Okay, the connection here is weak. The TV show plot assumes technology that is probably decades in the future.
The electronic implants for Parkinson's mess up the function of the brain's subthalamic nucleus (STN) and that probably causes greater impulsiveness.
DBS implants affect the region of the brain called the subthalamic nucleus (STN), which also modulates decision-making.
"This particular area of the brain is needed for what's called a 'hold-your-horses' signal," Frank said. "When you're making a difficult choice, with a conflict between two or more options, an adaptive response for your system to do is to say 'Hold on for a second. I need to take a little more time to figure out which is the best option.'"
We know that people differ greatly in ability to inhibit impulsive desires to carry out various acts. Do naturally occurring variations in the STN cause the naturally occurring variations in impulsiveness?
The STN, he said, detects conflict between two or more choices and reacts by sending a neural signal to temporarily prevent the selection of any response. It's this response that DBS seems to interrupt. DBS acts much like a lesion on the subthalamic nucleus. Frank's hypothesis predicted that DBS would negate the "hold-your-horses" response to high-conflict choices. Surprisingly, it actually sped up the decision-making process, a signature, he said, indicated of impulsive decision making.
Drugs used to treat Parkinson's also cause behavioral problems, but of a different sort. The Parkinson's drugs appear to prevent learning from negative experiences. Hey, what if some people who aren't even on Parkinson's drugs have a limited ability to learn from negative experiences? That might explain self-destructive behaviors that plague some people.
The tendency toward impulsive behavior in Parkinson's patients is well-documented but only dimly understood. How is the STN involved in decision-making and why should things go awry when you stimulate it"
For those taking them, medications did not slow down decision-making conflict. Regardless of whether these patients are on or off medication, for the purposes of the experiment they looked like healthy people or people who are off DBS.
But what Frank found was that medications prevent people from learning from negative outcomes of their choices. That could be one explanation for why patients develop gambling habits. If you learn from the positive outcomes instead of the negative, it could cause you to become a gambler.
"Whereas the DBS had no effect on positive v. negative learning, but it had an effect on your ability to 'hold your horses,' so it was a dissociation between two treatments which we think reveal different mechanisms of the circuit of the brain that we're interested in.
Know anyone who can't learn from their mistakes? Maybe they've got naturally occurring versions of negative outcomes learning disability.
These two reports suggest to me a big future role for preventative gene therapy. The first report provides preliminary evidence that gene therapy can lessen the symptoms of Parkinson's Disease.
MANHASSET, NY -- A novel gene therapy technique is safe and may be effective at staving off worsening symptoms of Parkinson's disease, according to the first scientific review of a dozen patients who have received the treatment over the last three years. The results were published in the latest issue of Lancet.
The patients, half of whom live on Long Island, are in advanced stages of the illness and were no longer responding to medicines when they signed on for the experimental therapy. The study was conducted by Andrew Feigin, MD, director of Neuroscience Experimental Therapeutics at The Feinstein Institute for Medical Research and his colleagues in collaboration with Parkinson’s scientists at New York Presbyterian Hospital-Weill Cornell Medical Center in Manhattan.
One woman and 11 men received a surgical infusion of fluid containing a viral vector and genes for a protein called GAD, glutamic acid decarboxylase. This enzyme is critical in controlling a neurotransmitter called GABA. In Parkinson’s, GABA is reduced in an area of the brain called the subthalamic nucleus. This region is working on overdrive in the disease process and GABA is an inhibitory transmitter and is important in trying to calm this hyper-reactive circuit.
This particular gene therapy does not fix the genes that are contributing to the development of Parkinson's Disease. But the good news is that the therapy appears to successfully deliver genes into brain cells.
The gene therapy would be used to reduce symptoms and not alter the underlying disease process. Finding novel therapies are key as many Parkinson’s patients stop develop complications after prolonged use of traditional medicines.The Feinstein’s David Eidelberg, MD, took brain scans before, during and after the treatment and the scans show that the brain is re-working these abnormal circuits. Dr. Feigin said that patients had about a 27 percent improvement in symptoms, although the study was an open label design. The scientists are now designing a double-blind placebo controlled trial that would enroll far more patients in an attempt to see whether the gene therapy is effective in reducing symptoms.
A far better gene therapy would target the genes that contribute to the development of Parkinson's in the first place. Well, a Mayo Clinic group used the rapidly falling costs of genetic testing to look at lots of genes in Parkinson's sufferers and they found combinations of genetic variations highly predictive for the development of Parkinson's Diseases.
“By examining a large cluster of related genes, we found patterns that make people up to 90 times more likely to develop Parkinson’s than the average person,” says study co-author Timothy Lesnick, a Mayo Clinic biostatistician. “The size of the effects that we observed for genes within a pathway and the statistical significance of the predictive models were unprecedented.”The models were highly effective in predicting age of onset of the disease: by age 60, 91 percent of patients in the highest-risk group already had Parkinson’s, while only 11 percent of patients in the lowest-risk group did. By age 70, every member of the highest-risk group had the disease, whereas two-thirds of patients in the lowest-risk group still were disease-free. Members of the highest-risk group typically developed Parkinson’s more than 20 years earlier than the lowest-risk group.
These two reports are a great example of why personal genome sequencing will become useful. Once brain gene therapy becomes a safe reliable technology anyone with a genetic profile which puts them at high risk of Parkinson's Disease (or Alzheimer's or assorted other brain disorders) will be able to get gene therapy decades before they develop clinical symptoms of a brain disorder.
Preventative gene therapy. That's what I want. Only, I want it for every cell in the brain and for every single thing that ages in the brain. Plus, I want it for the rest of the body. Then we can stop and turn back the clock of biological aging and become youthful again.
The development of gene therapy treatments for most of the maladies of old age (and probably all the neurological maladies) will eventually provide us with most of the tools we'll need for full body rejuvenation. Development of stem cell therapies and techniques for growing replacement organs will provide most of the other tools we need to turn back the aging clock.
Curcumin is a compound found in turmeric spice which is used in curries. While only done in cell culture the use of curcumin enhanced the performance of immune system macrophage cells to take up beta amyloid plaques.
UCLA/VA researchers found that curcumin — a chemical found in curry and turmeric — may help the immune system clear the brain of amyloid beta, which form the plaques found in Alzheimer's disease.
Published in the Oct. 9 issue of the Journal of Alzheimer's Disease, the early laboratory findings may lead to a new approach in treating Alzheimer's disease by enhancing the natural function of the immune system using curcumin, known for its anti-inflammatory and anti-oxidant properties.
Using blood samples from six Alzheimer's disease patients and three healthy control patients, the researchers isolated cells called macrophages, which are the immune system's PacMen that travel through the brain and body, gobbling up waste products, including amyloid beta.
The team treated the macrophages with a drug derived from curcumin for 24 hours in a cell culture and then introduced amyloid beta. Treated macrophages from three out of six Alzheimer's disease patients showed improved uptake or ingestion of the waste product compared to the patients' macrophages not treated with curcumin. Macrophages from the healthy controls, which were already effectively clearing amyloid beta, showed no change when curcumin was added.
It only helped in cells from half the patients.
"Curcumin improved ingestion of amyloid beta by immune cells in 50 percent of patients with Alzheimer's disease. These initial findings demonstrate that curcumin may help boost the immune system of specific Alzheimer's disease patients," said Dr. Milan Fiala, study author and a researcher with the David Geffen School of Medicine at UCLA and the VA Greater Los Angeles Health Care System. "We are hopeful that these positive results in a test tube may translate to clinical use, but more studies need to be done before curcumin can be recommended."
Older immune systems might be less able to clear the plaque junk that accumulates in the brains of those with Alzheimer's.
The patients ranged in age from 65 to 84. Fiala noted that the patients whose immune cells responded were younger and had higher scores on a Mini-Mental State Examination suggesting that curcumin may help those with less advanced dementia. Some of the patients may have already had additional curcumin in their systems due to participation in another UCLA study, which may have impacted findings.
Rejuvenation of the immune system will probably lower the incidence of Alzheimer's and might also reduce the incidence of other diseases caused at least in part by the accumulation of misfolded proteins and other junk. Check out some evidence that immune system aging leads to Alzheimer's: Immune System Deficiencies May Lead To Alzheimer's Disease
Also see my post Alzheimers Curable With Insulin Receptor Drug? for another approach that might help. Then there's the stoner approach to protection from Alzheimer's: THC Blocks Alzheimer's Plaque Formation
In preliminary results, researchers have shown that a drug which mimics the effects of the nerve-signaling chemical dopamine causes new neurons to develop in the part of the brain where cells are lost in Parkinson's disease (PD). The drug also led to long-lasting recovery of function in an animal model of PD. The findings may lead to new ways of treating PD and other neurodegenerative diseases. The study was funded in part by the NIH's National Institute of Neurological Disorders and Stroke (NINDS).
The study suggests that drugs which affect dopamine D3 receptors might trigger new neurons to grow in humans with the disease. Some of these drugs are commonly used to treat PD. The finding also suggests a way to develop new treatments for PD. The results appear in the July 5, 2006, issue of The Journal of Neuroscience. *
Parkinson's disease, a progressive neurodegenerative disorder that causes tremors, stiffness, slow movements, and impaired balance and coordination, results from the loss of dopamine-producing neurons in part of the brain called the substantia nigra. While many drugs are available to treat these symptoms during the early stages of the disease, the treatments become less effective with time. There are no treatments proven to slow or halt the course of PD. However, many researchers have been trying to find ways of replacing the lost neurons. One possible way to do this would be to transplant new neurons that are grown from embryonic stem cells or neural progenitor cells. However, this type of treatment is very difficult for technical reasons.
The new study, conducted by Christopher Eckman, Ph.D., and Jackalina Van Kampen, Ph.D., at the Mayo Clinic College of Medicine in Jacksonville, Florida, focused on a second possible way to restore function — prompting stem cells that normally remain dormant in the adult brain to develop into neurons.
The drug requires continual infusion.
"This is the first study to show that endogenous neurogenesis [development of new neurons from cells already in the brain] can lead to recovery of function in an animal model of Parkinson's disease," says Dr. Eckman.
The researchers gave either 2-, 4-, or 8-week continuous infusions of a drug called 7-OH-DPAT, which increases the activity of dopamine D3 receptors, into the brain ventricles of adult rats with neuron loss in the substantia nigra and symptoms similar to human PD on one side of the body. 7-OH-DPAT is not used in humans, but its effects on dopamine receptors are similar to the drugs pramipexole and ropinirole, which are approved to treat PD. The rats also received injections of a chemical called bromodeoxyuridine (BrdU), which marks proliferating cells, and infusions of a substance that fluorescently "traces" how neurons connect. The animals were tested before and 3 days after receiving the treatment to see how well they could walk and reach to retrieve food pellets with their paws. A subset of the rats was tested again 2 and 4 months following the treatment.
Rats treated with 7-OH-DPAT had more than twice as many proliferating cells in the substantia nigra as rats that were treated with saline, the researchers found. Many of the newly generated cells appeared to develop into mature neurons, and approximately 28 percent of them appeared to be dopamine neurons by 8 weeks after treatment. Animals treated for 8 weeks also developed almost 75 percent of the normal number of neuronal connections with other parts of the brain and showed an approximately 80 percent improvement in their movements and a significantly improved ability to retrieve food pellets. These effects lasted for at least 4 months after the treatment ended.
Similar drugs exist and the researchers are examining the effects of other drugs in rats as a prelude to trying therapies in human sufferers of Parkinson's. This result could turn out to yield an effective therapy without the need to solve the many problems involved with the development of adult or embryonic stem cells grown outside of the body.
In a paper published in Plos Medicine a team of researchers found that rises in the use of Prozac appear negatively correlated with suicide rates.
What Did the Researchers Do and Find?
They looked at annual suicide rates between 1960 and 1988 and compared them with annual rates in the period 1988 to 2002. They used several sources of data, including the Centers of Disease Control and the US Census Bureau. The researchers found that from the early 1960s until 1988, in the entire US population, between 12.2 and 13.7 people in every 100,000 committed suicide each year. After that time, the numbers of suicides gradually declined, with the lowest figure (10.4 people per 100,000) reached in 2000. The researchers did mathematical tests, which demonstrated that the steady decline was statistically associated with the increased number of fluoxetine prescriptions—that is, the more prescriptions there were, the fewer suicides there were. (There were around two-and-a-half million prescriptions of the drug in 1988, increasing to over 33 million in 2002.)
What Do These Findings Mean?
In all scientific research, it is an important principle that finding an association between two events does not prove that one caused the other to occur. However, the authors of this paper suggest that the use of this drug could have contributed to the reduction of suicide rates in the US in the period 1988 to 2002. Several other SSRIs are also now in common use, but they were not considered in this study, nor were other antidepressants, or other treatments for depression.
Prozac belongs to a class of anti-depressants known as Selective Serotonin Uptake Inhibitors (SSRIs). They work by blocking proteins on nerve cells that transport the serotonin into the nerves. That causes serotonin concentrations to rise in gap regions between nerves and ttherefore to bind instead to receptors to increase the effect of serotonin in sending messages that (at least in theory) will lighten moods.
Methods and Findings
Sources of data included Centers of Disease Control and US Census Bureau age-adjusted suicide rates since 1960 and numbers of fluoxetine sales in the US, since its introduction in 1988. We conducted statistical analysis of age-adjusted population data and prescription numbers. Suicide rates fluctuated between 12.2 and 13.7 per 100,000 for the entire population from the early 1960s until 1988. Since then, suicide rates have gradually declined, with the lowest value of 10.4 per 100,000 in 2000. This steady decline is significantly associated with increased numbers of fluoxetine prescriptions dispensed from 2,469,000 in 1988 to 33,320,000 in 2002 (rs = −0.92; p < 0.001). Mathematical modeling of what suicide rates would have been during the 1988–2002 period based on pre-1988 data indicates that since the introduction of fluoxetine in 1988 through 2002 there has been a cumulative decrease in expected suicide mortality of 33,600 individuals (posterior median, 95% Bayesian credible interval 22,400–45,000).
The introduction of SSRIs in 1988 has been temporally associated with a substantial reduction in the number of suicides. This effect may have been more apparent in the female population, whom we postulate might have particularly benefited from SSRI treatment. While these types of data cannot lead to conclusions on causality, we suggest here that in the context of untreated depression being the major cause of suicide, antidepressant treatment could have had a contributory role in the reduction of suicide rates in the period 1988–2002.
As the authors acknowledge, suggestions that there may be a causal relationship between fluoxetine prescription and suicide rates would represent an overinterpretation of the results. In a study like this, it is also important to consider other potential explanations for the fall in suicide rates, such as improvements in the economy or improved management of depression by primary-care providers. Moreover, as the study did not include people above 65 years of age, who are known to have an increased risk of suicide (especially in men) compared with younger people, the findings are limited to adults up to 65 years of age.
Another limitation of this study was the use of fluoxetine as a model of SSRI use. Several effective SSRIs have been introduced since the arrival of fluoxetine, and these newer SSRIs may have had an additional potential impact on suicide rates. Finally, although the authors used the best available data on the number of prescriptions of fluoxetine, these estimations are not very accurate in terms of actual intake of antidepressants. As there are no reliable figures available on adherence to drug prescriptions at the population level, the real effect of antidepressants on suicide rates is difficult to estimate.
Even if this result holds up and the SSRIs have prevented 33,000 deaths that is probably small potatoes compared to the benefits in reduce mortality that have flowed from use of statin drugs to lower cholesterol. However, if SSRIs are brightening moods then they are probably making a big economic impact by reducing the lethargy that comes with depression.
The replenishment of missing neurons in the brain as a treatment for Parkinson disease reached the stage of human trials over 15 years ago, however the field is still in its infancy. Researchers from Kyoto University have now shown that dopamine-producing neurons (DA neurons) generated from monkey embryonic stem cells and transplanted into areas of the brain where these neurons have degenerated in a monkey model of Parkinson disease, can reverse parkinsonism. Their results appear in the January 3 issue of the Journal of Clinical Investigation.
Studies of animal models of Parkinson disease as well as clinical investigations, have shown that transplantation of fetal DA neurons can relieve the symptoms this disease. However the technical and ethical difficulties in obtaining sufficient and appropriate donor fetal brain tissue have limited the application of this therapy.
These researchers previously demonstrated that mouse embryonic stem cells can differentiate into neurons when cultured under specific conditions. These same culture conditions, technically simple and efficient, were recently applied to primate embryonic stem cells and resulted in the generation of large numbers of DA neurons. In their current JCI study, Jun Takahashi and colleagues generated neurons from monkey embryonic stem cells and exposed these cells to FGF20, a growth factor that is produced exclusively in the area of the brain affected by Parkinson disease and is reported to have a protective effect on DA neurons. The authors observed increased DA neuron development and subsequently transplanted these neurons into monkeys treated with an agent called MPTP, which is considered a primate model for Parkinson disease. These transplanted cells were able to function as DA neurons and diminished Parkinsonian symptoms.
In an accompanying commentary, J. William Langston from the Parkinson's Institute, California, describes this study as a milestone in the development of stem cell technology but cautions that while the observations are encouraging, the reported number of surviving DA neurons was very low, only 1–3% of the cells surviving, well below the estimated number of DA neurons that survive after fetal cell transplants (approximately 10%). While this may be a difference observed between transplantation in monkeys and humans, Langston stresses that it may be necessary for far more DA neurons to survive and for that survival to be long lasting in order to render this approach as a useful therapy in humans.
Langston highlights that "clearly the study reported here will advance research aimed at validating the use of stem cells to treat neurodegenerative disease" and this is most welcome particularly as investigators face yet another presidential moratorium endeavoring to limit the number of human stem cell lines that can be used for future research and treatment.
There are more hurdles here than just making the cells more viable before implanting them. There is the other extreme: the cells should not divide too much and replace more cells than are needed. Also, the cells should replace cells only in the parts of the brain where Parkinson's Disease has caused losses. Though adding extra dopaminergic neurons in small numbers in other parts of the brain might not cause a problem (leaving aside the possibility that a person's personality might change and they might effectively become someone else).
Eventually this work is going to progress to the point that researchers will want to try human trials. In Japan human embryonic stem cell use will probably not elicit much political opposition. So my guess is this avenue of research will eventually progress all the way to useful human therapies. At that point expect a big political fight in the United States over therapeutic cloning to produce human embryonic stem cell lines.
Animal models of diseases are very useful for the development of disease treatments. To use embryonic stem cells in therapy research on other species one must first produce embryonic stem cells. This is difficult to do in some species. In this context it is worth noting that one month ago a team at the University of Pittsburgh reported producing cloned rhesus monkey embryos.
Using newer cloning techniques, including the "gentle squeeze" method described by South Korean researchers who earlier this year reported creating the first cloned human embryonic stem cell line, University of Pittsburgh scientists have taken a significant step toward successful therapeutic cloning of nonhuman primate embryos.
It is the first time researchers have applied methods developed in the Seoul laboratory to nonhuman primate eggs. Resulting cloned embryos progressed to the blastocyst stage, a developmental step in which the embryo resembles a hollow, fluid-filled cavity surrounded by a single layer of cells. Called the inner cell mass, this layer contains embryonic stem cells. Growth of a cloned nonhuman primate egg to the blastocyst stage is farther along the developmental spectrum than ever achieved before, Gerald Schatten, Ph.D., director of the Pittsburgh Development Center at Magee-Womens Research Institute, and his colleagues report.
It remains to be seen whether cells produced using this technique will be a useful source of monkey embryonic stem cells.
So how did the Japanese team get monkey embryonic stem cells for their research? My guess is embryonic stem cells from a conventionally initiated monkey pregnancy was the source. But does anyone reading this know for sure?
A fairly new type of magnetic resonance imaging (MRI), called diffusion tensor imaging (DTI), has been used to examine the brains of children diagnosed with attention deficit hyperactivity disorder (ADHD) and ADHD children were found to have abnormal fiber pathways that connect the different parts of the brain.
CHICAGO – Children with attention deficit hyperactivity disorder (ADHD) display anatomical brain abnormalities beyond chemical imbalance, according to research presented at the annual meeting of the Radiological Society of North America (RSNA). Stimulant medications prescribed to balance brain chemistry appear to normalize some of these brain irregularities, a second study reported.
"We found abnormality of the fiber pathways in the frontal cortex, basal ganglia, brain stem and cerebellum," said lead author of both studies, Manzar Ashtari, PhD., associate professor of radiology and psychiatry at North Shore-Long Island Jewish Health System in New Hyde Park, N.Y.
"These areas are involved in the processes that regulate attention, impulsive behavior, motor activity, and inhibition--the key symptoms in ADHD children," Dr. Ashtari said. "They are also known to be part of a bigger circuit in the brain that establishes communication between the frontal lobe and cerebellum."
According to the National Institute of Mental Health (NIMH), ADHD affects 3 to 5 percent of children in the United States. Children with ADHD have difficulty controlling their behavior or focusing their attention.
Using diffusion tensor imaging (DTI) to compare 18 children with diagnosed ADHD with 15 control children to evaluate the brain's white-matter fiber development, Dr. Ashtari's team found differences in the brain fiber pathways that transmit and receive information among brain areas.
"Typically ADHD is described as a chemical imbalance, but our research has shown that there may also be subtle anatomical differences in areas of the brain that are important in this disorder," said co-principal investigator Sanjiv Kumra, M.D., a psychiatrist at the Zucker Hillside Hospital in Glen Oaks, N.Y.
If DTI brain scanning can be used to diagnose ADHD then that could lower the rate of misdiagnosis and kids wouldn't be given drugs unnecessarily. The treatment of ADHD with stimulant drugs appears to have a beneficial effect on brain development!
In the second study, the researchers found that children who had received stimulant treatment for ADHD had fewer white matter abnormalities than children who did not receive medication.
Patients consisted of two groups, each comprised of 10 children with ADHD. The first group had not taken medication or had been minimally exposed to medications. The second group was exposed to stimulants for an average of 2.5 years. Each of these groups was compared with 10 age- and gender-matched controls. The medicated ADHD children exhibited a normalization effect in fiber pathways of several brain areas.
"The findings from this small, cross-sectional study indicate that the therapeutic effect of stimulants may involve a brain normalization process," Dr. Kumra said.
Between 3 percent and 5 percent of American children are diagnosed with ADHD.
The ability to use DTI to measure abnormalities of brains of children with ADHD will also allow comparison of different ADHD drug treatments to identify treatments that do a better job of reducing the size of the brain abnormalities.
WASHINGTON— Researchers at the Boston Veterans Affairs Health Care System – Brockton Division, Harvard Medical School, and the University of Massachusetts-Boston are using new imaging technology to gather valuable information about the brains of people with schizophrenia. This new variety of magnetic resonance imaging (MRI) is called diffusion tensor imaging (DTI). Using DTI on patients with schizophrenia, neuropsychologists have related smaller sizes in two distinct webs of brain fibers to two distinct types of cognitive malfunction.
The findings appear in the October issue of Neuropsychology, which is published by the American Psychological Association (APA).
Diffusion tensor imaging (DTI) uses a regular MRI machine to analyze the movement of water molecules in and around the fibers that connect different parts of the brain. Neuroscientists use DTI to track indicators of brain “connectivity” – factors such as the number, thickness, density and arrangement of axons (the hair-like extensions of neurons, which send messages to other neurons) and thickness of the insulating/conducting fatty myelin sheath in which they are embedded. If weaker structural integrity reduces connectivity, lead author Paul Nestor, PhD, says it may mean that, “different brain areas do not communicate as well – with less synchrony or harmony, akin to an orchestra or band playing out of synch.”
The researchers conducted neuropsychological tests on 41 patients with schizophrenia and 46 healthy controls, and used DTI scans on a 14-person subset of people with schizophrenia and healthy controls, a sample size typical of seminal studies of the human brain and comparable to early studies using functional MRI.
Brain images from the schizophrenic patients showed abnormalities in two functionally and anatomically different neural pathways – the uncinate fasciculus (UF) and the cingulate bundle (CB). Compared with age-matched controls, patients had smaller UF and CB. These bunches of axons are wrapped in myelin sheaths and bundled like electrical wire. The UF connects different parts of the frontal and temporal lobes and the CB connects parts of the prefrontal-cingulate regions. Each of these fiber tracts may help to define distinct neural networks. “We presume that the health of these fibers reflects the degree to which different parts of the brain are able to communicate,” says Nestor.
It seems reasonable to expect DTI will help to accelerate the development of drugs for schizophrenia as well. Comparison of patient brain scans before and after treatment will provide a way to compare the efficacy of different drugs in reducing brain abnormalities. To repeat a frequent FuturePundit refrain: advances in scientific and medical instrumentation enable the acceleration of advances in science and medical treatment.
Now, a UC Berkeley bioengineer has devised a way to enhance the utility of adult stem cells that could steal some of the spotlight away from embryonic stem cells and eventually lead to treatments or cures for diseases such as Alzheimer's and Parkinson's.
Schaffer's team took DNA from a rat and isolated the gene that produces the Sonic hedgehog protein. They then cloned that gene, inserted it into a harmless virus which they then injected into the rat's brain. The virus delivered the Sonic hedgehog genes to the brain stem cells, stimulating them to divide three times faster than normal, which in turn tripled the production of new neurons.
Researchers discovered a couple of years ago that Sonic Hedgehog is a major regulator of neuron cells. The body uses the Sonic protein in multiple tissues for development, such as the skin, hair, intestine, pancreas and brain, from the embryo stage to the adult stage. Schaffer’s investigation focuses on Sonic’s role in the brain.
“To regenerate tissue, or replace a lot of neurons, you need to mass-produce the cell, and then you need to take those mass-produced cells and induce them to differentiate them into neurons. So we’re very interested in Sonic Hedgehog because we found it’s a powerful way to mass produce the cells initially,” Schaffer said.
Parkinson's Disease and other brain diseases will some day be treated with stem cell therapies. Since neural stem cell growth appears to slow in people suffering from depression it is even possible that stimulation of neural stem cell growth could become a treatment for depression.
Neural stem cell growth appears to slow with age as well. Techniques to stimulate of neural stem cell growth may well become standard therapies to prevent the age-related decline in the ability to form new memories.
A couple of cautions however: First off, stem cells programmed to grow much more rapidly might grow too much and turn into neurons in locations they are not needed and even potentially harmful. Scientists will need to develop methods to not only stimulate cell growth but also to turn off the source of stimulation once the needed cells have been produced.
Also, stimulating old stem cells to grow more rapidly might not be wise if the old cells have accumulated a lot of DNA mutations. Old cells are at greater risk of becoming cancer cells because of the damage they have accumulated. So considerable care will be needed to in selecting older cells that can safely be stimulated into acting young again. One way to try to reduce the threat of cancer on old cells will be to do gene therapies to old stem cells to fix growth regulation genes that may have gotten dangerously mutated over a period of years.
Stanford researchers have shown in a preliminary non-double blind trial that the anti-depressant Selective Serotonin Uptake Inhibitor (SSRI) escitalopram (Lexapro) reduces the severity of kleptomania.
STANFORD, Calif. – Researchers at Stanford University School of Medicine are reporting promising early results in a study of a medication to treat kleptomania. More volunteers are needed for the confidential 24-week trial that, the researchers say, has curbed the urge to steal in the majority of patients who have entered the study so far.
“The preliminary results from the first patients to go through the study are even better than we expected,” said Elias Aboujaoude, MD, a clinical instructor in the Department of Psychiatry and Behavioral Sciences and one of the study investigators. “What we have seen so far is very impressive, with 78 percent of the patients responding to the drug in the open-label phase.” The open-label phase is when trial participants are aware that they are taking a particular drug and not a placebo.
Kleptomania, the guilt-ridden, impulsive stealing of inexpensive and unneeded items, often goes untreated as many who suffer from the disorder hesitate to seek help out of fear of being turned in for their illegal activities. More than 1.2 million people in the United States are thought to suffer from kleptomania. The condition differs from shoplifting, in which the action is usually planned, guilt-free and motivated by need or monetary gain. Kleptomania appears to affect more women than men, and the age of onset often dates back to childhood or adolescence.
Although the cause of kleptomania remains unknown, some researchers believe it involves disruptions of the brain neurotransmitter, serotonin. Earlier studies have suggested that a class of medications known as selective serotonin reuptake inhibitors, or SSRIs, can be effective in treating disorders with similar aspects, such as compulsive skin picking or compulsive shopping.
Lorrin Koran, MD, the professor of psychiatry and behavioral sciences who is leading the study, said it is the first double-blind, placebo-controlled test of a medication to treat kleptomania: in this instance, the study is researching the effect of the SSRI escitalopram, which is marketed as Lexapro and has been approved by the Food and Drug Administration for treating major depressive disorder.
SSRIs are being tried for a number of other obsessive compulsive disorders. For example, Stanford researchers have previous shown that the anti-depressant SSRI citalopram reduces the severity of obsessive compulsive shopping disorder.
Since so many people are taking SSRIs (e.g. Prozac, Zoloft, Paxil, Luvox, Celexa) it is quite possible that the incidence of obsessive compulsive disorders has dropped as a side effect of treating millions of people for depression.
BTW, if you are interested in taking SSRIs check out this table of SSRI side effect rates. There is no one SSRI that is best on all side effects for all people. Many depressed people have to try out a few SSRIs before finding one that works best.
Jeff Matovic, a 33 year old resident of Ohio, has experienced an enormous decrease in the twitches and uncontrollable movements caused by Tourette Syndrome.
CLEVELAND, April 1, 2004: A neurosurgical team at University Hospitals of Cleveland (UHC) has, for the first time in North America, applied a new surgical approach to the treatment of Tourette Syndrome, resulting in the immediate and nearly complete resolution of symptoms for the patient, who has suffered from this neurologic disorder since he was a child.
"We were genuinely amazed at the patient's response," says Robert J. Maciunas, MD, neurosurgeon at UHC and professor at Case Western Reserve University School of Medicine. He has used the technique called Deep Brain Stimulation (DBS) for the treatment of Parkinson's disease and tremor, and was impressed with this patient's dramatic reaction: the disappearance of the jerking motions, muscle tics and grunting associated with his Tourette's. "This technique holds great promise for patients suffering from this movement disorder, which often is diagnosed in childhood or early adolescence and can be completely debilitating."
Jeff Matovic, a Lyndhurst, Ohio, resident who grew up in Bay Village, was six years old when he was diagnosed with Tourette Syndrome, a neurobehavioral disorder characterized by sudden, repetitive muscle movements (motor tics) and vocalizations (vocal tics). Though standard therapy with medication controlled his movements for much of his boyhood, his condition severely worsened with age.
Prior to brain surgery, physicians at University Hospitals Movement Disorders Center mapped out regions of Jeff's brain, through MRI (magnetic resonance imaging) scans and 3-D computer images. Their goal was to locate the safest and most direct route to reach the cells inside the thalamus portion of the brain, involved in controlling Jeff's movements. By placing electrodes around those cells to deliver continuous high-frequency electrical stimulation, control messages are rebalanced throughout the movement centers in the brain. The electrodes are connected from the brain through wires under the skin (beneath the scalp, neck and upper chest) to an implanted battery just beneath the collarbone. In Jeff's case, since both sides of his body were affected by the movement disorder, he has electrodes implanted on both sides of his brain and tiny battery packs implanted on each side of his chest.
The doctors at University Hospitals of Cleveland are careful to point out that not everyone with Tourette Syndrome requires treatment. The first line of treatment is medication, which can be very effective. Surgical treatment is considered a last resort, and it is not clear how effective deep brain stimulation will ultimately prove for patients with this particular disorder.
In the United States, the Food and Drug Administration has approved deep brain stimulation for the treatment of Parkinson's disease, essential tremor and dystonia. "We've seen very positive responses in patients with Parkinson's disease. Studies of the DBS technique show that this stimulation can significantly reduce tremor and other symptoms in about three quarters of appropriately selected patients with Parkinson's." says Brian N. Maddux, MD, PhD, Jeff's neurologist at UHC and assistant professor at Case School of Medicine. "Patients with a different movement disorder called dystonia can take three months to respond to the electrical stimulation. We didn't know how Jeff would respond. Within hours after the stimulator was turned on, we observed the ceaseless movements become completely relaxed and he was able to walk normally. We were awestruck."
Matovic learned about the possibility of a surgical treatment and had to convince doctors to try this technique on his brain.
"They took a lot of convincing. They hadn't really done anything like this before for Tourette syndrome."
Even if only a small percentage of all Tourette sufferers need a surgical treatment the potential number of candidates for this treatment still runs into the thousands.
An estimated 200,000 people in the United States have Tourette, but only a small percentage suffer symptoms as severe as Matovic's.
Matovic shows he has an incredible drive to triumph over his disorder. In spite of his disorder Matovic managed to go to college, graduate, get married, and his wife is expecting a baby. Plus, he took it upon himself to find doctors to give him an experimental therapy involving brain surgery which previously had not been performed in the United States.