Biopeer

Newly found protein may be a key to Parkinson's treatment

Researchers at the University of Helsinki in Finland discovered a novel kind of protein in the neurotrophic factor family of proteins, called conserved dopamine neurotrophic factor (CDNF), that protects and rescues damaged neurons in patients suffering from Parkinson’s disease. In an experimental model of Parkinson’s disease, researchers injected a neurotoxin 6-OHDA into the striatum area of the brain in rats. The researchers found that a single injection of CDNF, six hours before the toxin delivery into the striatum, significantly prevented the degeneration of dopamine nerves in the brain and controlled the abnormal movement and behavior of the rats. When CDNF was administered four weeks after the toxin, researchers were able to prevent the degeneration of dopaminergic neurons and cure the behavioral imbalance. The researchers believe that neurotrophic factors like CDNF may have significant potential in the treatment of Parkinson’s disease as a neuroprotective, or even as neurorestorative therapy.

Researchers at the Ottawa Health Research Institute in Ontario found that neuronal death in Parkinson's disease occurs when a cellular enzyme called Prx2 is injured. The team conducted a study in mice in which a mitochondria-affecting toxin, MPTP, was used to create a condition similar to Parkinson’s disease. They found a chain of events in which the toxin turns on a cellular switch, called Cdk5, which then turns off Prx2. According to the researchers, the findings suggest that strategies to modulate Prx2 activity may serve as beneficial targets for treatment of Parkinson's disease. "This is of particular importance since Cdk5 is thought to have normal beneficial roles in neurons and modulating a relevant downstream target rather than Cdk5 directly may be a better therapeutic strategy with regard to this pathway," concluded the scientists.

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Constant electrical pulses could improve treament with brain "pacemakers"

Biomedical engineers at the Duke University's Pratt School of Engineering have claimed that rapid-fire electrical pulses strengthen the ability of brain "pacemakers" to reduce symptoms in people with Parkinson’s disease. Brain "pacemakers" are devices that use deep brain stimulation to drown out the irregular bursts of brain activity characteristic to the disease. According to the research, the rapid-fire pulses can create an "information lesion," or information barrier, that acts similarly to an actual surgical lesion used to treat neurological conditions. “Periodic bursts in the brains of people with tremor – which might follow a pattern such as ‘pop-pop-pop, silence, pop-pop-pop, silence’ - propagate pathological information within brain circuits. If you replace that instead with a constant ‘pop-pop-pop-pop-pop-pop,’ you have erased that pathological information,” said Warren Grill, the study's lead investigator.   

The Department of Environmental and Occupational Medicine at Aberdeen University Medical School, in Aberdeen, U.K., has recently discovered that over-exposure to pesticides could lead to Parkinson’s disease. Researchers evaluated data concerning 959 people with Parkinson's or Parkinson's-like syndromes. The evaluation was based on a questionnaire focusing on the levels of pesticide and mineral exposure. The results showed that people who were exposed to low-levels of pesticides were 13% more likely to have Parkinson's compared to people who had never been exposed. People exposed to high levels of pesticides were 41% more vulnerable to the condition. 

Research conducted by Peter Piper, a professor at the University of Sheffield, showed that sodium benzoate, a food and beverage preservative, could lead to Parkinson’s disease. The research showed that sodium benzoate disrupts the ability of mitochondria – the 'power stations' of a cell – to contain the oxygen leaks that create free radicals. Several studies have already linked free radicals to serious illnesses and the process of aging. “I suspect that it does not increase production of free radicals so that levels are going up dramatically. And the body has very successful systems for mopping up 99% of free radicals. But it is that 1% that could be the problem. Over the longer term, this is a major component of why we age and why we progressively lose function,” said Professor Piper.

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New diagnostic test for Parkinson’s disease

Researchers from the Howard Florey Institute, the University of Melbourne and the Mental Health Research Institute of Victoria, have devised a diagnostic test for Parkinson’s disease (PD), which would not only measure the levels of
'alpha-synuclein' protein in the blood, but also check the effect of candidate drugs in improving the level of the protein. If this blood test clears the clinical trials then there may be some hope in PD diagnosis to normalize the level of alpha-synuclein and bring many forms of PD to the forefront for efficient diagnosis.

Meanwhile, researchers at the Wellcome Trust Centre for Neuroimaging in London analyzed the effect of dopamine- related drugs on patients suffering from Parkinson’s disease (PD). The study included 39 healthy people, aged 18 to 39. Divided into three groups, they were administered levodopa, which increases dopamine levels in the brain, a dopamine receptor blocker called haloperidol (which decreases dopamine activity), and placebo respectively. Inference from the study was that dopamine drive leads people to compulsive behavior. The study is expected to look into the therapy that would control the effect of dopamine-related drugs, thereby controlling the compulsive behavior of PD victims.

A recent study on Parkinson’s disease (PD) claims to determine the impact of exercise in preventing the symptoms of PD. “The idea behind it is if we force them to pedal at a higher rate, this rate will allow them to have biochemical changes that are necessary for improvements in motor function. There's a possibility that there's an increase in dopamine, or there's a possibility that there's an increase in these neuro growth factors”, said Dr. Jay Albers of the Cleveland Clinic. Certain exercises like yoga, meditation improves the functioning of brain, and hence there are chances of exercise to ward-off the symptoms of PD in the primary phase.

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Mixed news on Parkinson's disease

Research into the treatment of Parkinson’s disease has both lowered and raised hopes.

In a big blow to Parkinson’s disease treatment, it has been found that two commonly prescribed anti-Parkinson’s drugs are unsafe for heart valves. The drugs pergolide and cabergoline belong to the ergot-derived dopamine receptor agonists class. These drugs cause damage when they interact with a receptor as this interaction compels the valve to grow beyond its normal size, resulting in it becoming floppy and leaky. In one study involving 11,000 people, Berlin researchers found that nearly 30 per cent of participants on either of the drugs were more likely to develop newly diagnosed cardiac-valve regurgitation. In a second study conducted on 245 participants, the Italian researchers found that 23 per cent of those on pergolide and 29 per cent of those on cabergoline had heart valve problems. On the other hand, those on non-ergot-derived dopamine agonists did not suffer from any such problem. Researchers hope that the US Food and Drug Administration (US FDA) will henceforth not permit doctors to prescribe these drugs.

On the other hand, researchers have also come up with an innovative skin patch to treat Parkinson’s disease. A six-month study on 277 participants throughout Canada and the United States concluded that the patch does alleviate symptoms in those with early stage Parkinson’s disease. The patch delivers the drug rotigotine directly through the skin. One of its main advantages over the pill is that it facilitates the steady and uniform delivery of the drug to the brain over a period of 24 hours. The German firm Schwarz Pharma markets the patch under the brand name Neupro. It is currently sold in Germany, Britain and Austria. The firm is expecting US FDA approval by June 2007.

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Studies uncover more secrets of Parkinson's disease

A new study in Japan has established that the epilepsy drug Zonegran helps Parkinson’s disease patients. Three groups of the 279 participants were given 25 mg, 50 mg or 100 mg of Zonegran every day while the fourth group received a placebo for 12 weeks. The group on the daily dose of 50 mg benefited the most. When the effects of the drug were measured using the Unified Parkinson’s Disease Rating Scale, it was found that the score of these patients improved by nearly 40 percent. However, drowsiness, weight loss and constipation were a few side effects observed.

Meanwhile, a recent American study by researchers from the University of North Carolina at Chapel Hill has connected low levels of low-density lipoprotein (LDL) cholesterol to Parkinson’s disease. The study involved 124 patients suffering from the disease and 112 participants who were spouses of other patients. The researchers examined fasting cholesterol profiles, smoking habits, age, gender and usage of cholesterol-lowering drugs of all the participants. They found that the occurrence of the disease increased 3.5-fold in those participants who had low levels of LDL when compared to participants with higher LDL levels.

Another American study from the San Francisco VA Medical Center has found one probable cause for the death of dopamine neurons in Parkinson’s disease. The research was carried out on mice genetically engineered to not have the gene responsible for HIPK2, a protein that controls how genes express themselves. The researchers observed that not having HIPK2 leads to TGFbeta3 being absent. Since TGFbeta3 is vital for brain and nerve cells to survive, its absence causes the death of dopamine neurons and the resultant damage to motor skills associated with Parkinson’s. The findings have opened up new possibilities for therapies.

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Studies continue on neurological diseases

Researchers have made advances in the studies of Huntington’s disease, amyotrophic lateral sclerosis (ALS) and Parkinson’s disease.

American researchers at the Mayo Clinic have identified a protein interaction that causes Huntington’s disease. While cholesterol delivery to the cell is vital, the mutant Huntington’s disease protein disrupts this system. This results in accumulation of cholesterol in the brain and leads to Huntington’s disease. However, this occurs only when the mutant protein is expressed with the molecule caveolin–1. When the researchers disabled this expression in experiments, the cholesterol accumulation stopped. The researchers are hopeful that their findings will lead to a treatment for this disease.

Meanwhile, researchers from the Muscular Dystrophy Association and the Translational Genomics Research Institute (TGen) have recognized 50 genetic abnormalities in ALS or Lou Gehrig's disease patients. They found these abnormalities when they screened and compared the DNA samples of over 1,200 people with sporadic ALS with those of 2,000 people without the disease. The screening revealed that motor neurons are attached to muscle with a molecular adhesive. When a person is suffering from ALS, the nerve peels off the muscle repeatedly, leading to the death of the nerve. The two organizations now want to find drugs that will act on the biochemical pathways found from the screen.

Scientists from the Columbia University, USA, have zeroed in on the reason for the stunted growth of neurons seen in Parkinson’s disease. They have found that the improper functioning of the protein made by mutant forms of the LRRK2 gene adversely affects neurons and causes them to die. The death of neurons is at the core of the disease. The researchers believe that their findings will aid in developing new treatments.

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Diagnostic research underway for neurodegenerative and kidney diseases

Significant studies conducted by American researchers have increased the potential of diagnostic testing.

Researchers at the University of Washington and Harborview Medical Center have found a way to diagnose neurodegenerative diseases like Alzheimer’s and Parkinson’s in their early stages. In a large multi-site study, the researchers used the proteomics system iTRAQ to identify and link more than 1,500 potential biomarkers in cerebrospinal fluid from patients with one of three neurodegenerative diseases: Alzheimer's, Parkinson's, or Dementia with Lewy bodies (DLB). However, the study will have to be conducted on a much larger scale before it could play its part in a diagnostic tool.

Researchers are also on their way to developing a skin test that could detect Alzheimer’s disease. Scientists from the Blanchette Rockefeller Neurosciences Institute in Maryland have discovered chemical changes that distinguish patients with early Alzheimer's from those with other neurodegenerative disorders. They found that the inflammatory chemical bradykinin produced chemical changes in the brain and skin cells of Alzheimer’s patients, which were different from those of patients suffering from diseases like Parkinson’s. These changes were best visible in the two enzymes ERK1 and ERK2. The researchers hope that the findings will lead to a non-invasive test for Alzheimer’s disease.

Meanwhile, researchers from San Francisco VA Medical Center have found that measuring the levels of cystatin C is a more accurate way to diagnose kidney disease than the standard kidney function test, which considers creatinine. They measured levels of cystatin C and creatinine in blood samples from 4,663 people, age 65 and older, and matched those results with health outcomes up to nine years later. It was found that those with high cystatin C levels were three times more likely to develop chronic kidney disease and 40 per cent more likely to suffer heart failure.

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Researchers widen genetic horizons

Three separate studies have made significant contributions to the field of genetics enabling possibly better treatments for Parkinson's disease and muscular dystrophy.

Researchers at the Karolinska Institute, Sweden, have zeroed in on mechanisms that may be one of the causes for Parkinson's disease. The team generated a mouse model in which the gene TFAM is automatically deleted from the genome in the dopamine nerve cells. Without TFAM, mitochondria cannot function properly. It was found that the mice born from genetically modified parents develop the disease slowly in adulthood, like humans with Parkinson's disease. The dopamine producing nerve cells in the brain stem slowly degenerated and that too, in a particular order. The researchers hope that the mouse model will help them to develop drugs that delay, or even stop the death of the nerve cells.

Meanwhile, researchers from the University of Virginia, USA, have found a way to reverse myotonic dystrophy, the most common form of muscular dystrophy (MD), in mice. They created mice with faulty DNA that could be turned on and off by adding or removing an antibiotic to their drinking water. In the "on" phase the mice showed all the cardinal features of myotonic dystrophy. When the DNA was turned off, normal skeletal and cardiac muscle function was restored. Although the treatment was not 100 per cent effective, the researchers believe that their results prove that it might be possible to reverse muscular dystrophy.

In another study, researchers from the University of Florida, USA, have found a new method of gene therapy for hereditary heart conditions, which has been proved successful in animal tests. The approach delivers corrective genes with a single injection into the veins. Tests conducted on mice and monkeys have been successful.

Genetic research continues to advance

In separate studies, researchers from two countries have widened the scope of genetics.

US scientists have found a mutation in a gene that is a major cause of Parkinson’s disease among Eastern European (Ashkenazi) Jews. Researchers from the Albert Einstein College of Medicine of Yeshiva University and Beth Israel Medical Center studied the gene LRRK2 in 120 unrelated Ashnekazi Jewish Parkinson’s disease patients. The participants were compared to a control group comprising 317 Ashenazi Jews who did not have the disease. The researchers extracted DNA from the participants and examined them for mutations. It was found that 18.3 per cent of the Jews suffering from the disease had the G2019S mutation while only 1.3 per cent of the control group had it. The mutation was also detected in 29.7 per cent of those who had a family history of the disease and in 13.3 per cent of the nonfamilial cases. The researchers believe that their findings establish the need for genetic counseling for Parkinson’s disease.

Meanwhile, in a first-of-its-kind achievement, US scientists have managed to reconstruct an ancient gene. Segments of two modern mouse genes, which descended from the ancient one, were combined to reconstruct the 530-million-year-old gene. The genes scrutinized in the study were Hox genes. The scientists claim that the reconstruction is further evidence of the steps of evolution and helps to demystify the process. They also hope that it will give way to a new kind of gene therapy that will be able to cure more diseases.

British researchers have identified why second hand smoke does not affect all children. The research team from the University of Dundee found that defects in the genes that produce glutathione-S-transferase (GST) make children susceptible to the harmful effects of environmental tobacco smoke exposure.

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Two steps forward in Parkinson’s disease research

Two studies conducted by US researchers have led to findings that could play a major role in understanding the cause of and in diagnosing Parkinson’s disease.

Researchers from Emory University, Atlanta, have found that exposure to the banned pesticide dieldrin could increase the risk of developing Parkinson’s disease (PD). The researchers administered 0.3 mg/kg, 1 mg/kg, 3 mg/kg of dieldrin or no dieldrin (placebo) every three days to pregnant mice throughout gestation and lactation. On analyzing brain samples they found that the pesticide alters the dopamine neuron equilibrium and increases the vulnerability of dopamine neurons to a parkinsonism-inducing toxin. This vulnerability affects more male than female rodent offsprings. The findings are significant because most studies aimed at determining the disease process in PD have focused on events occurring during adulthood, not during developmental stages. The study was led by the neurotoxicologist Dr Gary Miller, PhD, researcher in Emory's Center for Neurodegenerative Disease.

Researchers from the University of Florida have found that patients suffering from Parkinson's disease can be apathetic without being depressed, and apathy may be a core characteristic of PD. They compared 80 sufferers of PD to 20 sufferers of the movement disorder dystonia. They found that 51 per cent of the Parkinson's disease patients exhibited strong signs of apathy, compared to 20 per cent of the dystonia patients. Apathy without depression was observed in 29 per cent of the Parkinson's patients and not in any of the dystonia patients. The team, led by Lindsey Kirsch-Darrow, stated that apathy and depression share many of the same symptoms, which means they can be misdiagnosed. This can lead to the treatment of a disorder that the patient is not suffering from.

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