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Giorgiana Pavaloiu

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2639

Progress in multiple sclerosis research

New advances have been made in multiple sclerosis research by scientists at Northwestern University. A study, which was published in the journal Science Translational Medicine, shows that autoimmune attack on myelin in multiple sclerosis can now be kept under control with a new therapy.

Multiple sclerosis is an autoimmune disease characterized by destruction of myelin, an important component of neurons that plays a role in nerve transmission. This demyelination that occurs can lead to a number of signs and symptoms: numbness in hands or feet, impaired vision, dizziness, paralysis etc. Stephen Miller, the Judy Gugenheim Research Professor of Microbiology-Immunology at Northwestern University Feinberg School of Medicine, said the new therapy  blocks the autoimmune response which is already activated and prevents further activation of autoimmune cells. He added that what is really exciting is that this treatment does not affect the normal immune system function. Current therapies for multiple sclerosis involve drugs that suppress the entire immune system which increases the risk of infection and cancer.

multiple sclerosis research

multiple sclerosis research

The study led by Dr. Miller implied processing white blood cells of patients with multiple sclerosis to obtain myelin antigens. These white blood cells were then introduced into the body so that the immune system to recognize and develop tolerance to them. Although the study was conducted only on nine patients, it was showed that those who received the highest dose of the white cells had the highest rate of decrease in the reactivity of myelin.

Being a phase 1 clinical trial, the main aim of the research was to demonstrate the safety and tolerance of the treatment. It was found that intravenous injection of up to 3 billion white blood cells did not result in any adverse effect in patients with multiple sclerosis. In addition, what is of note is that the treatment did not reactivated the disease and did not interfere with the body’s immune function. In addition, the researchers wanted to see whether the effect of this immune therapy was specific for myelin. They therefore also tested the immunity of patients with multiple sclerosis to tetanus. The result was that patients’ response to tetanus remained strong, which demonstrated that immune therapy effect was specific for myelin.

Researchers want now to conduct the phase 2 clinical trial to test whether the new treatment may prevent the progression of multiple sclerosis in humans. “In the phase 2 trial we want to treat patients as early as possible in the disease before they have paralysis due to myelin damage.” Miller noted.

3328

The potential of stem cells in cartilage formation

Researchers at the University of Pennsylvania are investigating new ways to grow cartilage from stem cells. The study, published in the Proceedings of the National Academy of Sciences, is led by Associate Professor Jason Burdick (Department of Bioengineering in the School of Engineering and Applied Science) and Associate Professor Robert Mauck (Department of Orthopaedic Surgery in Penn’s Perelman School of Medicine), and shows that cadherin signal can stimulate chondrogenesis, which can be the starting point for the treatment of several degenerative joint diseases.

It is known that cartilage injuries are very difficult to repair and surgical approaches are currently limited. To repair a damaged cartilage, the surgeon takes a piece of cartilage from another area but this means to harm healthy cartilage which can have consequences later in life (as the person ages). Burdick said that the study aims to discover new methods of production of cartilage to repair small lesions, such as those of athletes and then find ways to get treatment for chronic injuries such as cartilage degradation that occurs with aging. He added that now they are trying to figure out which is the best environment for adult stem cells to produce cartilage. Mauck is optimistic regarding the therapeutic potential of stem cells. He said that the health and vitality of cartilage cells decrease as we age. Therefore the chances that adult chondrocytes to repair cartilage injuries are relatively low, and that stem cells are the solution.

cartilage

Cartilage

Researchers made several experiments on mesenchymal stem cells, a type of stem cells found in bone marrow that have the ability to differentiate into many cell types such as bone, fat or cartilage. Researchers have focused on finding signals to determine how to differentiate these cells. The first step in the growth of new cartilage consists in initiating chondrogenesis, which implies that the mesenchymal stem cells to differentiate into chondrocytes. Researchers found that an essential role in signal and interaction between these cells  is played by some molecules called cadherins.

To create conditions for growth of cartilage cells, researchers used a peptide sequence that mimics the cadherin interactions, which subsequently helps to differentiate mesenchymal stem cells. Mauck said that while the direct link between cadherin and chondrogenesis is not completely understood, however what is known is that the stimulation of these interactions makes more cartilage. “All together, these experiments provide a thorough demonstration that this cadherin signal can improve the chondrogenesis response when presented from a synthetic hydrogel”, Mauck said.

2583

Statins proved no clear benefit in elder patients

A new clinical review of Australian researchers show that cholesterol-lowering drugs may do more harm than good in older people. Statins are among the most prescribed drugs among elderly patients with atherosclerosis, heart disease or diabetes.

Statistics show that more than 40% of Australians over 65 take cholesterol-lowering drugs called statins: atorvastatin, simvastatin, rosuvastatin and others. Like any other drug, statins also have side effects such as nausea, abdominal pain, muscle weakness and liver damage (increased hepatic enzymes). To see how these drugs are tolerated by elderly patients, researchers at the University of Sydney and Royal North Shore Hospital, Associate Professor Sarah Hilmer and Dr Danijela Gnjidic, analyzed randomized and observational clinical studies.

Statins

Statins

It was found that in elderly patients who had not a heart attack or stroke, the effects of statins were unclear, while the side effects were common and appeared to have a greater impact in these patients. Dr Hilmer said that statins reduced the risk of premature death in patients who had heart attack or stroke, but in others there was no evidence that statins may help. Dr. Hilmer added that studies pointed out that up to 10% of patients taking statins had a kind of muscle pain, and sometimes it can happen that these side effects might lead to the inability to walk. In addition, what is interesting is that there were found associations between statins and an increased risk of diabetes and cognitive impairment. Related to this finding, Dr. Hilmer explained that a study showed that patients who stopped taking statins had an improvement in cognitive function.

Researchers believe that patients who have muscle pain, elevated hepatic enzymes (liver damage), extreme fatigue or those taking drugs that interact with statins, should discuss with their doctor the withdrawal of medication. Moreover, in those with severe adverse reactions such as rhabdomyolysis (severe muscle damage), the doctors must stop the medication immediately.

Dr Ken Harvey, Adjunct Associate Professor at  La Trobe University’s School of Public Health, said it is always helpful for doctors to regularly review the benefit-risk ratio of the drug, especially in older patients where adverse effects are more common. He added that it is important to consider the possibility of side effects especially in the elderly, because clinical trials in this segment of patients are limited. “Important non-drug advice, such as encouraging people to stop smoking, eat a nutritious diet, moderate their alcohol composition, keep active and maintain an appropriate body weight should always be promoted, regardless of age” he pointed out.

3107

Lambrolizumab offers new hope for advanced melanoma patients

Latest studies conducted by researchers at UCLA’s Jonsson Comprehensive Cancer Center reveal that a new drug called lambrolizumab has shown promising results in treating advanced melanoma. In addition to increasing the survival rate, it seems that the new drug is associated with milder side effects than other drugs that are included in standard chemotherapy. The study results were presented by Dr. Antoni Ribas, UCLA professor of medicine in the division of hematology-oncology, who led the research, at the meeting of the American Society of Clinical Oncology in Chicago.

melanoma patients

Melanoma

Although it is the rarest form of skin cancer (the most common skin cancers are non-melanoma skin cancers including basal cell carcinoma and squamous cell carcinoma), melanoma is associated with the worst prognosis. Until now several therapies have been tested, but none had promising results in the treatment of advanced stage melanoma.

To demonstrate the effectiveness of the new drug (lambrolizumab), researchers conducted a study that included 135 patients with advanced stage melanoma who were divided into 3 groups. It was found that 38% of patients treated with lambrolizumab had an improvement in cancer regardless of the dose of drug received. Overall, 77% of all patients had a tumor response. Although the study did not measure the average duration of response to the drug, however it was observed that the longest response was over one year.

Regarding side effects, lambrolizumab was associated with mild, manageable reactions. The most important were  fever, fatigue, skin rash, loss of skin color and muscle weakness. It must be mentioned that severe adverse effects occurred in 13% of cases: pulmonary and renal inflammation or thyroid dysfunction. Dr. Ribas said the study showed the highest rate of durable response of any drug they tested in melanoma treatment and that in addition, the side effects were mild compared to other drugs.

Normally, T cells, which are part of the immune system, detect and destroy the promoters of various infections and diseases. But some cancers such as melanoma are not detected by T cells, which causes them to proliferate continuously and to produce metastases. PD-L1 is one of the proteins on the surface of melanoma cells that helps them hide from T cells (in order not to be destroyed). Therefore, researchers have sought to create a molecule to block the protein. Lambrolizumab is an antibody that reactivates the immune system by blocking PD-L1 protein. This drug is now being investigated not only for treating melanoma, and other cancers such as lung cancer.

3492

A new regimen treatment for HPV-positive oropharynx cancer patients

Patients with HPV-positive oropharyngeal cancer may benefit in the future from a treatment less toxic than the current  Intensity-Modulated Radiation Therapy (IMRT), which is the standard treatment. The study results will be presented at the 49th Annual Meeting of the American Society of Clinical Oncology by Shanthi Maruri, who is first author on the study and an oncologist at the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center.

Oropharynx cancer refers to a malignant tumor that develops in the oropharynx, which is the middle portion of the neck. In general oropharynx tumors are either HPV-positive, that is associated with human papilloma virus, and which generally have a better prognosis, or  HPV- negative that are generally associated with smoking or alcohol. Signs and symptoms announcing such cancers are difficulty in swallowing, voice changes, coughing, pain or hearing changes, weight loss, fatigue and others. In general risk factors for oropharyngeal cancer are alcohol, smoking, exposure to asbestosis, infections with HPV and EBV (Epstein Barr virus), various genetic mutations. Treatment consists of removing the tumor in addition to chemotherapy and radiotherapy, but in some cases the cancer cannot be operated. Regarding oropharynx cancer, studies have shown that combination therapy consisting of radiotherapy and chemotherapy may be as effective as surgery.

pharynx

Pharynx

Now researchers at Fox Chase Cancer Center have completed a phase 2 clinical trial that aimed to identify those patients with HPV-positive oropharyngeal cancer who do not require total dose of radiation. The 90 patients included in the study received chemotherapy and treatment with cetuximab, a monoclonal antibody which is part of the targeted treatment. The patient’s response to initial treatment determines the dose of irradiation. Barbara Burtness, senior author on the study and chief of head and neck medical oncology at Fox Chase, said that patients who respond well to chemotherapy have high chances to respond well to radiotherapy. Therefore, using a total dose of irradiation in these patients (who respond well to chemotherapy) would mean an overtreatment.
The results showed that the majority of patients included in the study  tolerated well the induction chemotherapy and cetuximab treatment, and that 46% of them had complete clinical response. All these patients received a lower dose of radiation: 54 Gy compared with the standard dose of 66- 70 Gy. It was found that in these patients the rate of high-grade side effects due to irradiation (difficulty swallowing, dry mouth) was lower. Although the results are promising, it is still early to draw definitive conclusions.

2522

New ways to combat devastating effects of Stroke

Researchers at the University of Connecticut Health Center are investigating new methods to prevent the devastating effects of stroke data, which is a major source of disability. Dr. Louise D. McCullough, professor of neurology and neuroscience and director of stroke research, explained that the stroke does not kill you but most people say they would rather be dead than live for life with severe disabilities which prevent to care for themselves. Dr. McCullough added that such patients need assistance because most cannot get out of bed. Another important disability is that sometimes stroke affects speech centers in the brain and patients cannot speak anymore. The number of stroke survivors grow increasingly as global population becomes increasingly older.

stroke

stroke

Stroke is of two types: hemorrhagic stroke and ischemic stroke. Hemorrhagic stroke is rare but often more serious than  ischemic stroke. Ischemic stroke is the most common and occurs through the clogging of arteries in the brain due to an embolus or plaque. Signs and symptoms of stroke are weakness on one side of the body or face, inability to speak or understand, vision problems, etc.. Symptoms vary depending on which brain area is affected.

Research conducted by Dr. McCullough focused on ischemic stroke, the most common form of brain attack. Ischemic stroke is a medical emergency that can be treated with tissue plasminogen activator (tPA), a “clot-busting” medication. If this therapy is administered shortly after the occurrence of stroke, the chances of recovery are much higher. It should be noted that this drug cannot be given for patients with certain medical conditions.

Dr. McCullough said that nationwide only 5-8% of stroke patients receive tPA, so treatment is quite limited in these patients. She noted that there has not yet been found a drug to protect the brain after a stroke and that reperfusion is less effective because the brain is already affected.

There are many risk factors that lead to stroke and one of them is high blood pressure. Therefore, researchers are trying to find a way to reduce both the occurrence of stroke and its effects. However successful treatments in laboratory animals cannot be applied with the same success rate in humans. “We create a model, study it, go back to patients, then go back to research. Our overall goal is to someday say we have a new treatment that can make a difference in people’s lives”, said Dr. Lauren Hachmann Sansing, assistant professor of neurology.

4081

Imiquimod proves effective as Cervical Pre-Cancer Treatment

Cervical cancer in early stages can now be treated without the need for surgery as researchers at Vienna Comprehensive Cancer Center (CCC) developed a new innovative method based on Imiquimod. This new treatment has already been tested in clinical trials and it seems to be effective and well tolerated by patients. It is a well-known fact that infection with HPV, human papilloma virus, causes cervical intraepithelial neoplasia (CIN), which is the early stage of cervical cancer. HPV infection is one of the most common sexually transmitted infection along with gonococcal infection, chlamydia and others. HPV affects the genital area in both women and men but it can also affect other areas such as the mouth or throat. Sometimes HPV infection goes away without causing health problems in some individuals but in others HPV causes warts or various types of cancer.

Cervical Pre-Cancer

Cervical Cancer

Statistics show that in Europe more than 200 000 women are diagnosed each year with cervical intraepithelial neoplasia, and most of them are women aged between 20 and 30 years. In most cases, CIN 1, that is the early stage of cervical cancer, has mild manifestations and does not require specific treatment because it heals on its own ( it requires however careful monitoring). In more advanced forms (CIN 2 or 3), conisation is performed, which means that damaged tissues are excised in cone-shaped sections. This surgery intervention is the standard treatment for CIN 2 or 3, but it should be noted however that this intervention involves a risk of relapse. In addition to this complication, there is the risk of bleeding or infection and perhaps the most important complication is that of preterm birth risk.

To avoid these complications (premature birth, bleeding, infection), researchers have sought to develop a new method of treatment less risky. So they developed a form of topical treatment (suppositories) based on Imiquimod, an agent that alters local immune response. When it comes in contact with the cervix, this drug causes local inflammation that destroys damaged tissue areas.

Paul Speiser, senior physician in the Department of General Gynaecology and Gynaecological Oncology, part of the Comprehensive Cancer Center of the Medical University Vienna Vienna and head of the study, explained that HPV causes changes that are not always recognized by the immune system and these changes can lead to the development of CIN. Because of the local immune activation by imiquimod, these areas of dysplasia (CIN) can be recognized and destroyed by the immune system itself.

New treatment method was effective and was well tolerated by patients. Still further studies are needed before it can become routine treatment. “The initial data are very promising. The agent seems to be very effective in the treatment of a CIN 2 and 3, is simple to use in this application and is considerably less invasive than a surgical intervention”, researchers said.

3218

New treatment for amyotrophic lateral sclerosis

Researchers from the University of Wisconsin-Madison have managed to make some great progress in a disease so far considered untreatable and fatal: amyotrophic lateral sclerosis ( ALS). ALS also called motor neuron disease or Lou Gehrig’s disease, is a neurodegenerative disease characterized by muscle weakness, muscle atrophy, fasciculations and other progressive neurological deficits.

Theer are several possible causes of this  neurological disease although it is not clear why ALS occurs. It is assumed that the possible etiological factors are exposure to certain chemicals, exposure to electromagnetic fields or various traumas or electric shocks. There have been studies that have shown a link between prions (prions are abnormal proteins involved in transmissible spongiform encephalopathies) and ALS or elevated glutamate (found in both serum and cerebrospinal fluid in patients with ALS). According to the ALS Association, about 5,000 Americans are diagnosed each year with this disease, and of these 50% are alive at three years after diagnosis.

amyotrophic lateral sclerosis

amyotrophic lateral sclerosis

Masatoshi Suzuki, assistant professor of comparative biosciences year, and his team of researchers at the UW School of Veterinary Medicine, used stem cells from adult human bone marrow and, after they genetically engineered these cells to produce growth factors to nourish damaged neurons, they transplanted them directly into the muscles of rats suffering from ALS.

Suzuki said he  turned his attention to the neuromuscular junction because it seems that this is the site where neurological damage in ALS begins. He said: “We know that the neuro-muscular junction is a site of early deterioration, and we suspected that it might be the villain in causing the nerve cell to die. It might not be an innocent victim of damage that starts elsewhere.”

In previous studies Suzuki found that injecting glial cell line-derived neurotropic factor (GDNF) at the neuromuscular junction helps neurons survive. Now the new study comes to show that vascular endothelial growth factor has a similar effect as GDNF. In this way, it was found that the delivery of vascular endothelial growth factor using stem cells improves survival and delays disease onset. The real advantage is that stem cells can generate both growth factors. Suzuki said that the combination was powerful than single growth factor in terms of disease-free time, overall survival, and sustaining muscle function, and that the results offer a new chance people with this fatal disease.  Researchers believe that replacing neurons remains a challenge, but now their goal is to keep neurons alive and health with the same growth factors that the body gives.

2934

Levosimendan proves safe and effective

According to a study presented at the Heart Failure Congress 2013,  levosimendan, a calcium sensitiser, improves event free survival by 50% compared with placebo in patients with end stage cardiac failure. Furthermore, another study showed that the third generation mineralocorticoid receptor antagonist (MRA) BAY 94-8862 is effective in patients with chronic kidney disease and heart failure. Levosimendan is a drug that increases heart sensitivity to calcium, which means that it increases cardiac contractility without increasing the level of calcium in the heart. Besides the positive inotropic effect, levosimendan also has vasodilatory effect (because it acts on potassium channels and induces smooth muscle relaxation) and a cardioprotective effect.

Management of patients with congestive heart failure is difficult on the one hand because each patient responds individually to treatment and on the other hand because patients usually have multiple comorbidities (kidney disease, liver disease, digestive diseases associated etc). Therefore, researchers conducted a multicenter study (LevoRep)  to investigate the efficacy and safety of levosimendan, a calcium sensitiser, in patients with congestive heart failure. It should be noted that LevoRep is the largest study of ambulatory administration of an inotrope drug in patients with end-stage heart failure.

Drugs

Drugs

The study included 120 patients with congestive heart failure who received biweekly either levosimendan (0.2 mcg / kg / min for 6 hours) or placebo. Results showed that levosimendan administered ambulatory was safe and effective in patients with end stage cardiac failure because it improved event free survival by 50% compared with placebo. This was the secondary endpoint of the study. However, it must be said that in terms of functional capacity and quality of life, levosimendan did not bring benefits. In other words the primary endpoints of the study were not met. Dr Gerhard Poelzl (Austria) said the further studies with more patients and with higher doses or higher repetition frequencies of levosimendan, could have positive results in terms of primary endpoints.

Another study was a randomized, double-blind,  phase 2 trial (MinerAlocorticoid Receptor Antagonist Tolerability Study) conducted on patients with chronic heart failure and chronic kidney disease. First and second generation of MRA have limited indications in such patients because of side effects (hyperkalemia, worsening renal function). However, the third generation MRA (BAY 94-8862) is considered to be less harmful to the kidneys. Study results showed that BAY 94-8862 is safe and well tolerated regardless of the dose used (2.5, 5, or 10 mg once daily or 5 mg twice daily). Professor Faiez Zannad (France) added that: “Future studies will investigate BAY 94-8862 novel indications: patients with heart failure and either moderate CKD or diabetes hospitalized for worsening chronic heart failure, and kidney protection in diabetics.”

2821

New insights into mechanisms of Parkinson’s disease

Latest studies on laboratory animals conducted by researchers at the German Center for Neurodegenerative Diseases (DZNE) in Bonn reveal new pathogenic mechanisms of Parkinson’s disease. Parkinson’s disease is the second most common neurodegenerative disease after Alzheimer’s disease. We already know that a key role in the development of Parkinson’s disease is represented by the protein ‘alpha-synuclein’ that aggregates and accumulates in neurons affecting different areas of the brain. Pathogenic mechanism underlying this degenerative disease is not fully known but one hypothesis is that it may result from an abnormal protein spreading along nerve tracts of the nervous system.

Now experiments conducted by researchers from the German Center for Neurodegenerative Diseases (DZNE) in Bonn provide new keys about the mechanisms of this disease. They created a new experimental model to reproduce the formation of ‘alpha-synuclein’ in neurons. They were able to reproduce the formation of human alpha-synuclein in rats and track the spread of this protein in the lower parts of the brain to the upper parts. The new experimental model could be the basis for the development of therapies to halt the progression of Parkinson’s disease.

Brain

Brain

Parkinson’s disease is a disease of the nervous system characterized both by motor symptoms (akinesia, motor disorders, tremors, etc.) but also by non-motor symptoms (trouble sleeping, depression, behavioral disorders, etc.). There have not been yet found a drug to cure Parkinson’s disease until the present, but there is treatment to control symptoms and to slow someway disease progression, such as dopamine agonists.

The causes are related to both genetic factors and environmental factors, although the exact cause of this disease is not known exactly. An interesting finding regarding the possible etiology of the disease was that of Friedrich Lewy, a German neurologist, who first discovered that the brains of patients with Parkinson’s disease contain some neuronal inclusions that accumulate progressively (and which were called Lewy bodies).

Studies so far have shown that the formation of alpha-synuclein aggregates begin in “medulla oblongata”, that is in the lower areas of central nervous system and then these aggregates migrate in midbrain and in  cortical areas, which referes to more rostral brain regions. To learn more about these aggregates, researchers monitored the production and localization of human alpha-synuclein in rats’ brains over a period of approximately 4 months after injection of viral particles. It was found that the production of human alpha-synuclein occurs only in neurons connected to the vagus nerve, and the overproduction of this protein occurs in conditions of aging, neuronal injury, genetic polymorphisms that might promote Parkinson’s disease.