Promising results from a team of NewYork-Presbyterian Hospital/Weill Cornell Medical Center physician-scientists show that gene therapy is both safe and effective at slowing the progression of Batten disease, or Late Infantile Neuronal Ceroid Lipofuscinosis (LINCL), a rare, genetic, degenerative neurological disorder that usually becomes fatal in children by the age of 8 to 12.

The clinical trial found that the procedure — which involves injecting a harmless gene-bearing virus into the brain — was not only safe, but, on the average, significantly slowed the disease progression of the subjects tested. Neurological function was assessed using a rating scale throughout an 18-month follow-up period.

“The virus is used as a Trojan horse that houses and then delivers a healthy, functional gene into the cells of the brain,” says lead author Dr. Ronald Crystal, chairman of the Department of Genetic Medicine and chief of the Division of Pulmonary and Critical Care Medicine at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. “The genes are incorporated within the genetic material of the cells, which are then able to produce a protein that is deficient in Batten disease.”

Dr. Crystal is a world leader and pioneer in the use of gene therapy to treat a number of genetic disorders and diseases.

The results are published in the May 13 online issue of Human Gene Therapy.

The gene in question — CLN2 — is mutated in children with the disease, causing a deficiency in the enzyme TTP-1, which is responsible for ridding cells of the central nervous system of waste materials. Small organelles within the cell, called lysosomes, become clogged with toxic material within the neurons of the brain.

“It’s like the garbage man of the cell is not able to do its job,” says Dr. Crystal. “The trash keeps getting backed up inside the cell until the cells can no longer function properly and then eventually die throughout the entire brain.”

When this happens, children with the disease begin exhibiting neurological symptoms, starting around age 4, including impaired muscle coordination (ataxia), involuntary twitching (myoclonus), and speech and developmental disorders. A gradual decline in visual ability follows. Affected children generally become wheelchair-bound by the ages of 4 to 6 years and eventually become bedridden.

Because the disease is fatal early in life, there are only about 200 cases of the disease in the world at a given time. Subjects from around the world were carefully selected to take part in the trial.

Neurological surgeons from NewYork-Presbyterian Hospital/Weill Cornell Medical Center, led by Drs. Mark Souweidane and Michael Kaplitt, performed the gene therapy procedure. Six tiny holes were made in the skull of each subject, and then a liquid containing the healthy CLN2 gene, within the harmless adeno-associated virus (AAV), was injected into the brain.

“Before now, we had no hope of a therapy for Batten disease, but today we can say that there is some hope,” says Dr. Crystal. “These results are not just promising for sufferers of the disease, but suggest that gene therapy can work and should be studied for other neurological disorders. Each gene in our body has the potential to become a target to study for human disease.”

Co-researchers include Dr. Stefan Worgall, Dr. Dolan Sondhi, Dr. Neil R. Hackett, Dr. Barry Kosofsky, Dr. Minal V. Kekatpure, Dr. Nurunisa Neyzi, Dr. Jonathan P. Dyke, Dr. Douglas Ballon, Dr. Linda Heier, Dr. Bruce M. Greenwald, Dr. Paul Christos, Dr. Madhu Mazumdar, Dr. Mark M. Souweidane and Dr. Michael G. Kaplitt — all from NewYork-Presbyterian/Weill Cornell.

NewYork-Presbyterian Hospital/Weill Cornell Medical Center

NewYork-Presbyterian Hospital/Weill Cornell Medical Center, located in New York City, is one of the leading academic medical centers in the world, comprising the teaching hospital NewYork-Presbyterian and Weill Cornell Medical College, the medical school of Cornell University. NewYork-Presbyterian/Weill Cornell provides state-of-the-art inpatient, ambulatory and preventive care in all areas of medicine, and is committed to excellence in patient care, education, research and community service. Weill Cornell physician-scientists have been responsible for many medical advances — from the development of the Pap test for cervical cancer to the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., the first clinical trial for gene therapy for Parkinson’s disease, the first indication of bone marrow’s critical role in tumor growth, and, most recently, the world’s first successful use of deep brain stimulation to treat a minimally-conscious brain-injured patient. NewYork-Presbyterian, which is ranked sixth on the U.S.News & World Report list of top hospitals, also comprises NewYork-Presbyterian Hospital/Columbia University Medical Center, Morgan Stanley Children’s Hospital of NewYork-Presbyterian, NewYork-Presbyterian Hospital/Westchester Division and NewYork-Presbyterian Hospital/The Allen Pavilion. Weill Cornell Medical College is the first U.S. medical college to offer a medical degree overseas and maintains a strong global presence in Austria, Brazil, Haiti, Tanzania, Turkey and Qatar.

NewYork-Presbyterian Hospital
Weill Cornell Medical Center Continue reading →

Canadians have one of the highest rates of Multiple Sclerosis (MS) in the world with approximately 1,000 new cases diagnosed each year. Primarily striking in adulthood, physicians and researchers with the Canadian Pediatric Demyelinating Diseases Network (CPDDN), a multi-institutional and multidisciplinary group, have found that MS is being increasingly diagnosed in children. A study by the CPDDN published in the journal Neurology, identifies a particular gene involved in the immune response that puts certain children at a higher risk of developing MS.

In children, an initial attack of demyelination (acquired demyelinating syndrome [ADS] in the central nervous system) often remains a single, isolated episode. However, in at least 20 % of children it represents the first clinical attack of MS. This contrasts with adult-onset MS, where most individuals presenting with acute demyelination are subsequently diagnosed with MS. Demyelination is the destructive loss of myelin – the protective covering that insulates and supports nerve cells – damaging the cells’ ability to receive and transmit signals in the body.

“The uncertainty of the diagnosis understandably creates a lot of anxiety for children and their families,” says Dr. Amit Bar-Or, neurologist and lead investigator at The Montreal Neurological Institute and Hospital – The Neuro, McGill University. “Having the tools to distinguish ADS and MS is important.” Researchers at The Neuro in collaboration with researchers at the SickKids in Toronto and international colleagues therefore wanted to identify the risk factors in the 20% of children who go on to develop MS, and to investigate if the risk factors and the disease biology are the same in both children and adults.

In adults, complex interactions between genetic and environmental factors contribute to risk and the best established genetic susceptibility marker has been identified in the alleles of the major histocompatability complex, a family of genes that play an important role in the immune system and autoimmunity. Specifically, the genetic risk factor for adults of northern European origins is localized to a form of the gene known as the HLA-DRB1 allele. The researchers wanted to verify if this allele predicts MS in at-risk children with ADS. Children, aged 16 or younger (266 children with ADS and 196 healthy controls) provided blood samples for genetic analysis.

“What we found is that there is a higher frequency of HLA-DRB1 in children that would later be diagnosed with MS, but not in children presenting with a single episode of ADS. This indicates that this gene is a risk factor in pediatric-onset MS.” Children with ADS that do not go on to develop MS had no difference in HLA gene expression from controls indicating that the gene confers an increased risk for pediatric-onset MS, but not for acquired demyelination in general.

This is one of several studies investigating pediatric MS as part of the CPDDN. As children with pediatric MS are closer to the early mechanisms and biology of the disease, they can also provide insights into factors that represent causes versus consequences of the disease. One in 20 adults with MS can trace the disease back to a pediatric event, and therefore have had the disease for many years. This study reveals a fundamental similarity in genetic contribution to MS risk in both pediatric and adult-onset disease and underscores the importance of understanding the etiology of MS in children providing the possibility for earlier diagnoses and intervention and hopefully new therapies for MS.

Source:
Anita Kar
McGill University Continue reading →

Oxygen Biotherapeutics, Inc. (OTC Bulletin Board: OXBO) announced that the company has received approval from Israel’s Ministry of Health to begin a Phase II-b, dose escalation, clinical trial in that country for use of Oxycyte(R) in traumatic brain injury (TBI). Oxycyte is the Company’s perfluorocarbon (PFC) therapeutic oxygen carrier.

“This approval from the Israeli Ministry of Health means that we can begin enrolling patients in a second country with a first class health care system,” said Chris Stern, company chairman and CEO. “We hope this trial can provide data to show that Oxycyte is of invaluable importance in improving the outcome of patients, both civilian and military, with severe TBI. It is our goal to finally prove that there is a safe and effective treatment for this devastating injury.”

The clinical trial with four centers in Israel is part of a larger study that also includes seven trial centers in Switzerland. The company has named the 128 patient study “Safety and Tolerability of Oxycyte in Patients with Traumatic Brain Injury” or “STOP TBI.”

The dose escalation studies will focus on finding the lowest dose of Oxycyte that provides clinical benefit in traumatic brain injury while minimizing adverse effects. Dose levels of Oxycyte would start at 1.0 ml/kg body weight and escalate in steps to 2.0 ml/kg, and 3.0 ml/kg for subsequent patient cohorts. Escalation of dose will only occur after a favorable review of safety data by an independent Data Safety Monitoring Board.

About Oxygen Biotherapeutics, Inc.

Oxygen Biotherapeutics, Inc. is dedicated to commercializing innovative pharmaceuticals and medical devices in the field of oxygen therapeutics and Defense Medicine(TM). The company has under development a perfluorocarbon (PFC) therapeutic oxygen carrier and liquid ventilation product (Oxycyte(R)) and has out-licensed an implantable glucose sensor. These products are based upon core technologies that include biomedical applications for PFCs as well as medical and industrial applications for biosensors. Each of the product candidates is designed with advantages over currently marketed products in major markets including traumatic brain injury, sickle cell crisis, trauma, wound care, decompression sickness, acute respiratory distress syndrome, stroke, myocardial infarction, surgery, diabetes wounds and ulcers, and cosmetic applications.

Source: Oxygen Biotherapeutics, Inc Continue reading →

By combining three previously unrelated imaging tools into one new device, a team of researchers from the University of Connecticut and the University of Southern California has proposed a new way to diagnose early-stage ovarian cancer in high-risk women through minimally invasive surgery. The new technique may be better than the current standard procedure of preemptively removing the ovaries.

Ovarian cancer has a low survival rate because a lack of reliable screening techniques usually means the disease remains hidden until the later stages. Now researchers have drawn on the unique advantages of multiple imaging tools to test a new way of spotting early-on the tissue irregularities that signal cancer.

For their diagnostic device, the researchers combined the contrast provided by photoacoustic imaging, the high-resolution subsurface imaging provided by optical coherence tomography, and the deeper tissue imaging provided by pulse-echo ultrasound. They tested their device, described by the team in the September issue of the Optical Society’s (OSA) open-access journal Biomedical Optics Express, by imaging both pig and human ovarian tissue, and correctly identified malignant tumors that were later confirmed by staining the tissue and examining it under a microscope. These initial tests were performed on tissue that had been surgically removed, but the diameter of the device – at only 5 mm – is small enough that it could potentially be inserted through a small slit to image tissue in live patients. Continue reading →

Wine drinkers in England are consuming about 2,000 calories just from booze each month, according to a new study. A significantly large proportion of these people are not aware of the calories that pile up when consuming wine. They are the equivalent to consuming an extra 38 roast beef dinners or 184 bags of crisps.
Implications for women

42% of women do not know that a glass of white wine has the same number of calories as a bag of crisps, according to the Government’s Know Your Limits campaign.
Two large glasses of white wine represent more than the daily recommended alcohol limit for women.
At 370 calories, two large glasses of wine make up nearly one fifth of an average woman’s daily calorie allowance.

Implications for men

40% of men not know that a pint of lager has the same number of calories as a sausage roll.
A man who consumes five pints of lager a week is consuming an extra 44,200 calories per year.
5 pints of lager a week are equivalent to the calories of 221 doughnuts in one year.

Alcohol makes people hungry, adding even more calories

37% of drinkers say that alcohol triggers them to eat more.
Over a third of drinkers say that on a day they drink over the daily recommended limit they are much more likely to ditch a healthy diet.
29% of drinkers order nuts, pork scratching, or crisps when they are having an alcoholic drink.
19% of drinkers will regularly grab a takeaway (takeout) pizza, burger, kebab or bag of chips (French fries) when they consume over two glasses of wine or two pints of beer.

More calories the morning after
According to the new Know Your Limits figures, people tend to consume more calories the following morning.

62% of people who usually have muesli or a bowl of cereal for breakfast will go for less healthy options to help them through a hangover. 28% say they turn to a fry-up, bacon or sausage sandwich, or takeaway breakfast from a fast-food chain. Swapping a bowl of cereal for a fry-up can add an extra 450 calories, on top of the alcohol calories consumed the night before.

Health Minister, Phil Hope said “Regularly drinking more than our recommended daily limits can have a knock on effect on our health – including an expanding waistline. It’s not only the calories in the drinks themselves that can help to pile on the pounds, we’re also more likely to eat fatty foods when we’ve had one too many. To avoid piling on the pounds we should try to drink within the recommended limits, eat a healthy diet and exercise regularly.”

Heather Caswell, spokesperson for the British Nutrition Foundation said “Many women don’t know that two large glasses of white wine not only puts them over the recommended daily limit for alcohol consumption, but also provides them with nearly 20 per cent of their daily calorie allowance, at approximately 370kcals in total. Most people would baulk at consuming a full glass of single cream, but wouldn’t think twice about a couple of pints. But the calorie content is similar and, over time, excess alcohol intake is likely to lead to weight gain. Sticking to sensible drinking habits and keeping to the recommended units will not only help keep off those extra pounds but will also help decrease your risk of serious health problems, such as some types of cancer and liver disease.”
Here are some tips from the British Nutrition Foundation:

Adhere to the maximum daily recommended units for alcohol consumption – 3 to 4 units per day for men and 2 to 3 units per day for women. A 250ml glass of wine with an alcohol content of 12% contains 3 units of alcohol, while a pint of beer with an alcohol content of 5.2% contains 3 units.
To prevent you becoming dehydrated, alternate between an alcoholic drink and a glass of water.
Try not to drink on an empty stomach. However, try to pick foods that are good for you.
Drink at your own pace rather than in rounds – you most likely consume more if you drink in rounds.
If you are trying to cut down your alcohol consumption, you are more likely to succeed long-term if you do so with a friend.
Have a healthy meal before you start drinking. You are less likely then to grab calorie filled snacks later on.
Take small sips rather than large gulps.
Do not save your units for the end of the week. If you do you are binge drinking – this is very bad for you.
Mix non-alcoholic liquids in with your drink. If you are having a glass of white wine add some soda water.

Know Your Limits is a joint Department of Health and Home Office initiative, launched in October 2006

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A vaccine for treating a recurrent cancer of the central nervous system that occurs primarily in the brain, known as glioma, has shown promising results in preliminary data from a clinical trial at UCSF Medical Center.

Findings from the first group of six patients in the study, being conducted at the UCSF Brain Tumor Research Center, showed that vitespen (trademarked as Oncophage), a vaccine made from the patient’s own tumor, was associated with tumor-specific immune response in patients with recurrent, high-grade glioma.

Glioma is a type of primary tumor that arises from the glial cells, the connective tissue cells that surround and support nerve cells. The most common site of involvement of a glioma is the brain. Malignant glioma is currently a fatal disease.

The trial results were presented at the Immunotherapy Task Force Meeting, sponsored by the Society of Neuro-Oncology and the Joint Section of Tumors, during the Society’s 11th annual scientific meeting in Orlando, Fla., on November 16, 2006.

“This is the first documentation of a glioma-specific immune response after vaccination with vitespen,” said Andrew T. Parsa, MD, PhD, assistant professor in the UCSF Department of Neurological Surgery and principal investigator of the trial.

“Based on preliminary observation of patients in the first cohort, the tumor-specific immune response evoked by vitespen vaccination may be associated with clinical benefit in these patients with recurrent glioma, including improved progression-free survival and overall survival compared with historical controls. Further studies are certainly warranted to definitively determine the benefit of vitespen in this patient population,” he said.

Derived from each individual’s tumor, vitespen contains the “fingerprint” of the patient’s particular cancer and is designed to reprogram the body’s immune system to target only cancer cells bearing this fingerprint. The vaccine is intended to leave healthy tissue unaffected and limit the debilitating side effects typically associated with traditional cancer treatments such as chemotherapy and radiation therapy. Vitespen has been granted fast track and orphan drug designations from the Food and Drug Administration in both metastatic melanoma (skin cancer) and renal cell carcinoma (kidney cancer).

The UCSF clinical trial is a phase1/2 study designed to establish the feasibility, safety and preliminary efficacy of vaccination in patients with recurrent, high-grade glioma. The trial involves two groups of six patients, both of which receive a minimum of four injections: the first group receives biweekly vaccinations and the second receives weekly vaccinations. Patients are monitored for immune response before, during and after treatment.

In the first group, study results showed tumor-specific immune response was detected after vaccination in all six patients. Researchers observed that patients whose disease was stable after surgical resection and before vaccination were more likely to respond clinically. Of the first six patients treated, five have exceeded the historical median benchmark of 6.5 months survival from time of recurrence. All six have exceeded the overall survival historical benchmark of 14.6 months from time of diagnosis.

The UCSF investigators will continue to follow patients for progression-free survival and overall survival. According to investigators, no adverse events or toxicity identified were considered attributable to the vaccine. Based on these preliminary findings, a larger phase 2 study is planned for 2007.

Rosalind Hekkala, a 66-year-old woman from Reno, Nev., who was enrolled in the first study group, was originally diagnosed with a brain tumor in July 2005. She had surgery to remove it, but the tumor returned in November. Her daughter learned of the trial at UCSF and Hekkala enrolled. In January 2006 she had another surgery, and this time, the removed tissue was sent to Antigenics, the Massachusetts biotech company that produces the vaccine from the patient’s tumor tissue. Because of the size of the tumor, Hekkala will receive injections every other week until mid-February. So far, results are promising with no sign of tumor regrowth, according to the Parsa.

“Every day I feel better,” Hekkala said on a recent visit to UCSF to receive her injection. “I set small goals for myself and I keep meeting them. I am very hopeful that this vaccine is the answer.”

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The clinical trial was funded the American Brain Tumor Association and the National Cancer Institute’s Specialized Program of Research Excellence.

UCSF is a leading university that advances health worldwide by conducting advanced biomedical research, educating graduate students in the life sciences and health professions, and providing complex patient care.

Contact: Carol Hyman

University of California – San Francisco Continue reading →

About 1000 Australian males and females of all ages were tested for their ability to detect or identify a range of different odours at different concentrations, and then given an overall score for their sense of smell, or olfactory function.

The results showed that olfactory function deteriorates relatively slowly with age in those who do not smoke, take medications or have a history of nasal problems such as sinusitis.

However the ability to smell drops off much quicker in older people who were taking medications – also an indicator of underlying health problems.

Researcher Dr Amy Johnston, from Griffith University’s School of Nursing and Midwifery and the Eskitis Institute of Cell and Molecular Biology, said the study suggested that aging alone had a small detrimental effect on smell.

“However our sense of smell is vulnerable to both the direct effects of some medications and changes associated with a number of neurodegenerative illnesses. Exposure to these factors typically increases with age.”

Anticholesterol and blood pressure lowering medications were amongst the common drugs known to interfere with smell. Conditions such as Parkinson’s disease and Alzheimer’s disease were also associated with impairment in the sense of smell, she said.

Dr Johnston said the ability to smell was an important factor in the enjoyment of food flavours.

“People who lose their sense of smell, particularly the elderly, are at risk of poor appetite and subsequent poor nutrition. Smell is also an important warning sense – telling people when food is not fit for consumption.”

Healthy women were shown to have a more sensitive sense of smell than healthy men but the gender effect was not apparent in smokers, people on medications or with a history of nasal problems.

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The study was published in the journal Chemical Senses. Dr Johnston and other members of the Clinical Neurology group continue their research focusing on the impact of common medications on the sense of smell.

Contact: Dr. Amy Johnston
Research Australia Continue reading →

Eric Shaqfeh studies blood at Stanford University, using computer models that simulate how the fluid and the cells it contains move around. On November 11 at a meeting of the scientific society AVS, he will present his latest unpublished findings from two studies. One shows how components in blood line up to prepare for healing; the other demonstrates the best shape to use for man-made nanoparticles that target cancers — a surfboard.

The different components that move through our blood stream are not evenly distributed. For years, scientists have known that platelets — which help blood to clot — stay close to the walls of blood vessels as they circulate.

“When somebody cuts himself, the fact that the platelets are sitting seven times more frequently at the edges of the little blood vessels is critical,” says Shaqfeh.

His models suggest that when a new platelet is made, it takes longer than expected to migrate to and line up at the edge — as much as ten or fifteen minutes to establish “hemostatis,” in which blood cells are properly distributed in the body. The research, funded by the Army, suggests that current techniques for blood transfusions may not be ideal. Freezing platelets, which is common practice, may change their shape and disrupt their movements, and there may be better ways to give transfusions that establish the proper blood arrangement faster, says Shaqfeh.

In related work, Shaqfeh added tiny nanoparticles of various sizes and shapes into his blood models. Such particles are of interest to the cancer researchers, who hope to use nanoparticles to target the walls of blood vessels that feed tumors. Shaqfeh found that surfboard-shaped particles stayed closest to the walls of blood vessels. He will soon be working with another group to test fluorescent surfboard-shaped particles in actual blood vessels to see how they behave.

The talk “The Microfluidics of NonSpherical Colloidal Particles and Vesicles with Application to Blood Additives” is at 11:20 a.m. on Wednesday, November 11, 2009. Abstract

Full meeting program

Main meeting page

Source: Jason Bardi

American Institute of Physics Continue reading →

When forming myelin, oligodendrocytes have a big job in creating all that membrane. Specialized proteolipid protein (PLP) components of myelin membranes are expressed in the absence of neurons, but an unknown diffusible neuronal factor triggers a switch in PLP trafficking.

This week, Kippert et al. investigated the trafficking of PLP from late endosomes/lysosomes (LEs/Ls) to the plasma membrane. The authors used Oli-neu cells, an oligodendroglial line stably expressing fluorescently labeled PLP (PLP-EGFP). Conditioned media from primary neuronal cultures triggered cell differentiation and PLP-EGFP redistribution. Inhibition of tyrosine kinases or Rho GTPase also triggered PLP-EGFP movement, and the addition of neuronal-conditioned medium reduced RhoA activity.

In immature oligodendrocytes, Rho mediated clathrinin-independent endocytosis, but upon differentiation, Rho activity and the endocytotic pathway were downregulated in favor of LE/L vesicle mobilization. The authors propose that endocytosis is a control point for the massive requirement for membrane in myelin.

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Angelika Kippert, Katarina Trajkovic, Lawrence Rajendran, Jonas Ries, and Mikael Simons

Source: News tips from the Journal of Neuroscience

Contact: Sara Harris
Society for Neuroscience Continue reading →

If you are going on a long plane trip you could benefit from wearing sunglasses as they can reduce the effects of jet-lag, say researchers from the Edinburgh Sleep Centre, Scotland. It seems that by altering your light patterns you can tweak your body-clock to adjust to new time zones more easily.

Researchers examined one thousand passengers on long-haul flights. They found that for every hour difference when you travel westwards it takes a day to recover from the effects of jet-lag (without sunglasses).

Dr. Chris Idzikowski, study leader, said that jet lag is a physical thing – not something made up. He said the biological clock is 20,000 nerve cells in the brain.

The researchers found that travellers recovered faster if they wore sunglasses during some their trip.

When you travel westwards your day is much longer. If you fly from London to New York, your 24 hour day becomes a 29 hour day. When you travel east the day becomes shorter. Travelling eastwards is harder to recover from.

The researchers have devised a chart which tells passengers how long they should wear their sunglasses for, depending on their trip.

Dr Idzikowski said “The internal body clock steps up at dawn which is when we can manipulate exposure to light, it’s a way of fooling the biological clock.”

He added that immigration officials often ask you to take your sunglasses off – this can weaken the benefits.

This study was carried out by the Edinburgh Sleep Centre on behalf of British Airways.

edinburghsleepcentre

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