Researchers at the University of California, San Diego School of Medicine have identified a new biomarker that predicts whether glioblastoma – the most common form of primary brain cancer – will respond to chemotherapy.

“Every patient diagnosed with glioblastoma is treated with a chemotherapy called temozolomide. About 15 percent of these patients derive long-lasting benefit,” said Clark C. Chen, MD, PhD, vice-chairman of Academic Affairs, Division of Neurosurgery, UC San Diego School of Medicine and the study’s principal investigator. “We need to identify which patients benefit from temozolomide and which another type of treatment. All therapies involve risk and the possibility of side-effects. Patients should not undergo therapies if there’s no likelihood of benefit.”

To pinpoint which patients were most likely respond to temozolomide, the researchers studied microRNAs that control the expression of a protein called methyl-guanine-methyl-transferase or MGMT. This protein dampens the cancer-killing effect of temozolomide. Tumours with high levels of MGMT are associated with a poor response to temozolomide therapy.

The scientists systematically tested every microRNA in the human genome to identify those that suppressed MGMT expression, with the expectation that high-levels of these microRNAs in the tumour would predict improved therapeutic response to temozolomide.

“We showed that a signature of the MGMT-regulating microRNAs predicted temozolomide response in a cohort of glioblastoma patients. Validation of these results should lead to diagnostic tools to enable us to determine which patients will benefit most from temozolomide therapy,” said Chen.

In the study, the scientists also discovered that injection of the MGMT-regulating microRNAs into glioblastoma cells increased tumour sensitivity to temozolomide treatment.

“These findings establish the foundation for microRNAs-based therapies to increase the efficacy of temozolomide in glioblastoma patients,” said lead author, Valya Ramakrishnan, PhD, postdoctoral researcher, UC San Diego School of Medicine. University of California – San Diego

A recent breakthrough in understanding the cause of a rare, hard-to-treat allergic disorder has been made by a group of research institutions that include the University of Arkansas for Medical Sciences (UAMS) and the Arkansas Children’s Hospital Research Institute (ACHRI).

The discovery could lead to new targeted therapies for eosinophilic eophagitis (EoE). The allergic/immune condition causes inflammation of the oesophagus, usually from consuming foods such as dairy products, eggs, soy and wheat.

The condition can cause infants and toddlers to refuse food and hinder their development. Older children may have recurring abdominal pain, vomiting and trouble swallowing, while teenagers and adults typically have difficulty swallowing. Food may also become stuck in the inflamed oesophagus, creating a medical emergency.

Existing treatments for EoE are limited to prescribing long-term restrictive diets and steroid sprays to swallow.

“We hope this discovery will open the door to some additional treatment options,” said Stacie Jones, M.D., a professor in the departments of Pediatrics and Physiology & Biophysics in the UAMS College of Medicine. She is also section chief of Allergy & Immunology and leads the allergy research team ACHRI.

The study found that EoE is triggered by the interaction between epithelial cells, which help form the lining of the oesophagus, and a gene called CAPN14. It also identified a marker that can be used to measure the activity of the disease, said UAMS’ Robert Pesek, M.D., an author on the study and an assistant professor in the Department of Pediatrics in the UAMS College of Medicine. 

“Currently, the only tool we have for measuring that is endoscopy, and that becomes impractical for repeated use on children,” Pesek said.

Although new treatments have yet to be realized, UAMS’ participation in EoE and other food allergy research gives Arkansas patients access to cutting-edge research and treatment expertise not available anywhere else in the state. University of Arkansas for Medical Sciences

In a new study, scientists at the National Institutes of Health took a molecular-level journey into microtubules, the hollow cylinders inside brain cells that act as skeletons and internal highways. They watched how a protein called tubulin acetyltransferase (TAT) labels the inside of microtubules. The results answer long-standing questions about how TAT tagging works and offer clues as to why it is important for brain health.
Microtubules are constantly tagged by proteins in the cell to designate them for specialized functions, in the same way that roads are labelled for fast or slow traffic or for maintenance. TAT coats specific locations inside the microtubules with a chemical called an acetyl group. How the various labels are added to the cellular microtubule network remains a mystery. Recent findings suggested that problems with tagging microtubules may lead to some forms of cancer and nervous system disorders, including Alzheimer’s disease, and have been linked to a rare blinding disorder and Joubert Syndrome, an uncommon brain development disorder.
‘This is the first time anyone has been able to peer inside microtubules and catch TAT in action,’ said Antonina Roll-Mecak, Ph.D., an investigator at the NIH’s National Institute of Neurological Disorders and Stroke (NINDS), Bethesda, Maryland, and the leader of the study.
Microtubules are found in all of the body’s cells. They are assembled like building blocks, using a protein called tubulin. Microtubules are constructed first by aligning tubulin building blocks into long strings. Then the strings align themselves side by side to form a sheet. Eventually the sheet grows wide enough that it closes up into a cylinder. TAT then bonds an acetyl group to alpha tubulin, a subunit of the tubulin protein.
Some microtubules are short-lived and can rapidly change lengths by adding or removing tubulin pieces along one end, whereas others remain unchanged for longer times. Recognising the difference may help cells function properly. For example, cells may send cargo along stable microtubules and avoid ones that are being rebuilt. Cells appear to use a variety of chemical labels to describe the stability of microtubules.
‘Our study uncovers how TAT may help cells distinguish between stable microtubules and ones that are under construction,’ said Dr. Roll-Mecak. According to Dr. Roll-Mecak, high levels of microtubule tagging are unique to nerve cells and may be the reason that they have complex shapes allowing them to make elaborate connections in the brain.
For decades scientists knew that the insides of long-lived microtubules were often tagged with acetyl groups by TAT. Changes in acetylation may influence the health of nerve cells. Some studies have shown that blocking this form of microtubule tagging leads to nerve defects, brain abnormalities or degeneration of nerve fibres. Since the discovery of microtubule acetylation, scientists have been puzzled about how TAT accesses the inside of the microtubules and how the tagging reaction happens.
To watch TAT at work, Dr. Roll-Mecak and her colleagues took high resolution movies of individual TAT molecules interacting with microtubules in real time. They saw that TAT surfs through the inside of microtubules and although it can find acetylation sites quickly, the process of adding the tag occurs very slowly.
In general, tagging reactions work like keys fitting into locks: the better the key fits, the faster the lock can open. Similarly, the rate of the reactions is determined by how well TAT molecules fit around tagging sites.
Dr. Roll-Mecak’s team investigated this idea by using a technique called X-ray crystallography to look at how atoms on TAT molecules interact with acetylation sites on tubulin molecules. Their results suggested that TAT fit poorly around the sites.
‘It looks as though TAT can easily journey through microtubules spotting acetylation sites but may only label those that are stable for longer periods of time,’ said Dr. Roll-Mecak.
This may help cells identify the microtubules they need to rapidly change shapes or send cargo to other places. Further studies may help researchers understand how microtubule tagging influences nerve cells in health and disease. National Institute of Neurological Disorders and Stroke

Latest figures by the International Diabetes Federation (IDF) have shown that an average 20% of the GCC population and nearly 19% of the UAE population now live with diabetes, with a marked increase in type II diagnoses. Coupled with this rise in disease prevalence, the Health Authority Abu Dhabi (HAAD) is forecasting nearly fourfold increase of healthcare cost for UAE nationals between 2010 and 2030. 
With the pancreas transplantation solution (that involves implanting a healthy pancreas, one that can produces insulin, into an insulin-dependent diabetic patient who is at risk of severe complications) being considered as a more accessible therapy for diabetic patients, the Arab Health Congress, running alongside Arab Health in January 2015 in Dubai, brings together leading practitioners in the field to discuss approaches to address the social and economic burden of the regional rising rate of the disease. 
Commenting on the potentially groundbreaking role of drug discovery and transplantation therapies ahead of his speech at the Arab Health Congress, Dr Mikel Prieto, Surgical Director of the Kidney and Pancreas Transplant Program and Paediatric Kidney Transplantation Medical Director of International Practice Operations at the Mayo Clinic said: “Pancreas transplantation has come of age in the 21st century. The results of this relatively rare type of transplant are outstanding with graft and patient survival rates well above 90 percent. This procedure represents an excellent option for the type of diabetic patients who have significant difficulty controlling their blood sugar or who have developed kidney disease as a consequence of their diabetes. Today, we can offer them a pancreas transplant or a combined pancreas and kidney transplant. This will free them from the need to inject themselves with insulin several times a day.”
World Diabetes Day, which took place on the 14^th of November, was also a reminder of the need for urgent action to fight against the disease in order to prevent the rate of diabetes in the Middle East from doubling in the next 20 years. The IDF estimates the adult population in the MENA region will increase from 375 million in 2013 to 584 million by 2035, with diabetes sufferers rising from 34.6 million to 67.9 million.

Epilepsy is a brain disorder which afflicts more than 50 million people worldwide. Many epilepsy patients can control their symptoms through medication, but about 30% suffer from intractable epilepsy and are unable to manage the disease with drugs. Intractable epilepsy causes multiple seizures, permanent mental, physical, and developmental disabilities, and even death. Therefore, surgical removal of the affected area from the brain has been practiced as a treatment for patients with medically refractory seizures, but this too fails to provide a complete solution because only 60% of the patients who undergo surgery are rendered free of seizures.

A Korean research team led by Professor Jeong Ho Lee of the Graduate School of Medical Science and Engineering at the Korea Advanced Institute of Science and Technology (KAIST) and Professor Dong-Seok Kim of Epilepsy Research Center at Yonsei University College of Medicine has recently identified brain somatic mutations in the gene of mechanistic target of rapamycin (MTOR) as the cause of focal cortical dysplasia type II (FCDII), one of the most important and common inducers to intractable epilepsy, particularly in children. They propose a targeted therapy to lessen epileptic seizures by suppressing the activation of mTOR kinase, a signalling protein in the brain.

FCDII contributes to the abnormal developments of the cerebral cortex, ranging from cortical disruption to severe forms of cortical dyslamination, balloon cells, and dysplastic neurons. The research team studied 77 FCDII patients with intractable epilepsy who had received a surgery to remove the affected regions from the brain. The researchers used various deep sequencing technologies to conduct comparative DNA analysis of the samples obtained from the patients’ brain and blood, or saliva. They reported that about 16% of the studied patients had somatic mutations in their brain. Such mutations, however, did not take place in their blood or saliva DNA. 

Professor Jeong Ho Lee of KAIST said, “This is an important finding. Unlike our previous belief that genetic mutations causing intractable epilepsy exist anywhere in the human body including blood, specific gene mutations incurred only in the brain can lead to intractable epilepsy. From our animal models, we could see how a small fraction of mutations carrying neurons in the brain could affect its entire function.” KAIST