Diabetes drug use during pregnancy may increase risk of obesity or overweight in children

In continuation of my update on metformin

When women take the common diabetes medication metformin during pregnancy, it may put their children at increased risk of having obesity or overweight.

A growing number of pregnant women are taking metformin to treat gestational diabetes or a condition called polycystic ovary syndrome (PCOS). PCOS is a common cause of infertility and can put women at risk of developing diabetes and other metabolic health problems. PCOS affects an estimated 7 percent to 10 percent of women of childbearing age, according to the Hormone Health Network.

When pregnant women with PCOS or gestational diabetes take metformin, the medication crosses the placenta and is passed to the fetus.

"Our findings indicate the offspring of women who took metformin for PCOS during pregnancy are more likely to meet the criteria for obesity or overweight than children whose mothers were given a placebo during pregnancy," said the study's first author, Liv Guro Engen Hanem, M.D., of the Norwegian University of Science and Technology in Trondheim, Norway. "The results were surprising, since limited past research in this area had suggested metformin would have a protective effect on the children's metabolic health."

The researchers invited parents of 292 children who participated in two previous randomized clinical trials to be part of this study. In the previous trials, pregnant women with PCOS were assigned to take either metformin or a placebo during pregnancy. The researchers wound up reviewing body mass index (BMI) and other measurements for 161 children born following the two earlier studies.

At four years of age, the children whose mothers were randomized to metformin during pregnancy tended to weigh more than the children whose mothers took the placebo. Although metformin did not appear to affect birth weight, the trend became apparent when children reached six months of age. At the age of four years, the children in the metformin group had higher BMI scores and were more likely to meet the criteria for obesity or overweight than children in the placebo group.

"Few studies have examined the long-term health of children born to women with PCOS who took metformin," Hanem said. "Our findings indicate more research is needed to determine its effects on children who were exposed in the womb."

Ref : https://www.endocrine.org/news-room/2018/diabetes-drug-use-during-pregnancy-linked-to-childs-weight

Diabetes drug use during pregnancy may increase risk of obesity or overweight in children

Failed osteoarthritis drug may help lessen opioid dependence

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A new study from Indiana University suggests that a drug proven safe for use in people may prevent opioid tolerance and physical dependence when used in combination with opioid-based pain medications.

Researchers in the Linda and Jack Gill Center for Biomolecular Science at IU Bloomington have discovered that a compound previously tested to treat osteoarthritis pain appears to block neuropathic pain and decrease signs of opioid dependence. The work is reported in the journal Molecular Pharmacology.

Human trials of the drug to treat osteoarthritis pain conducted by Indianapolis-based drug manufacturer Eli Lilly and Co. found that the drug lacked efficacy. However, the drug's use in treating other kinds of pain and lessening opioid dependence had not been tested before.

"The potential to quickly begin using this compound in combination with opioid-based medication to treat pain and reduce addiction makes this discovery very significant," said lead investigator Andrea G. Hohmann, a Linda and Jack Gill Chair of Neuroscience and professor in the IU Bloomington College of Arts and Sciences' Department of Psychological and Brain Sciences. "We already know this drug is safe for use in people, so moving into human trials will not require as many regulatory hurdles."

The need for non-addictive alternatives to opioid-based pain medication is urgent due to the rapid rise in overdose deaths over the past decade. According to the Centers for Disease Control and Prevention, over 64,000 Americans died from drug overdoses in 2016, including from illicit drugs and prescription opioids. To tackle this issue, IU last year launched the Responding to the Addictions Crisis Grand Challenge initiative to invest $50 million to prevent and reduce addictions in Indiana.

To test the potential of the experimental drug to treat pain and reduce addiction symptoms, IU scientists administered the compound and the opioid morphine to male mice with neuropathic pain. While morphine initially reduced the pain, mice quickly developed tolerance to morphine's effectiveness, similar to people who require higher doses of opioid over time to achieve relief.

Ref : http://molpharm.aspetjournals.org/content/93/2/49

Failed osteoarthritis drug may help lessen opioid dependence

Aspirin appears to reduce risk of death, hospitalization for people with heart failure and diabetes

In continuation of my update on aspirin and its uses..

For people living with both Type 2 diabetes and heart failure, taking an aspirin each day appears to lower the risk of dying or being hospitalized for heart failure, according to research being presented at the American College of Cardiology's 67th Annual Scientific Session. But the data also reveal aspirin use may increase the risk of nonfatal heart attack or stroke, a somewhat contradictory finding that surprised researchers.

The study is the first to assess aspirin as a preventive measure for patients who have both diabetes and heart failure. Aspirin, a blood thinner, is strongly recommended for patients who have previously had a heart attack or stroke, but guidelines are unclear regarding its use as a preventive measure for patients who have cardiovascular risk factors but no history of heart attack or stroke. Previous studies in people who have not had those types of health events have shown conflicting evidence of aspirin's potential benefits in the general population. In patients with heart failure, some studies suggest a daily aspirin may even be harmful.

About 27 million people in the U.S. have Type 2 diabetes and about 6.5 million U.S. adults have heart failure, a condition in which the heart becomes too weak to pump enough blood to meet the body's needs. Each condition is associated with an elevated risk of cardiac events, including heart attack and stroke. This study sheds new light on the potential risks and benefits of aspirin for people with both conditions.

"We were surprised to see a paradoxical increase in nonfatal heart attacks and nonfatal stroke, parallel to the decrease in mortality," said Charbel Abi Khalil, MD, PhD, assistant professor of medicine at Weill Cornell Medicine-Qatar and the study's lead author. "This finding might be due to the fact that those patients lived longer; given their mean age of 70 years, perhaps these patients were predisposed to more cardiac events."

Using data from a United Kingdom database known as The Health Improvement Network (THIN), researchers extracted health records of more than 12,000 patients ages 55 and older who had Type 2 diabetes and heart failure but no prior history of heart attack, stroke, peripheral artery disease or atrial fibrillation. Roughly half had been prescribed daily aspirin and half had not.

Researchers analyzed health outcomes over an average of five years of follow-up. All-cause mortality and hospitalization for heart failure were tracked as a composite primary outcome. All-cause mortality, hospitalization for heart failure, major bleeding events and nonfatal heart attack or stroke were tracked separately as secondary outcomes. Those taking a daily aspirin were found to show a 10 percent decrease in the primary outcome, no difference in major bleeding events, and a 50 percent increase in nonfatal heart attack or stroke.

Aspirin interferes with blood's ability to clot, by reducing the activity of platelets, which aggregate during clot formation. Heart failure and diabetes cause changes in the blood that make clot formation more likely, which is why these conditions are associated with a higher risk of heart attacks and strokes.

"Both heart failure and diabetes are associated with increased blood clotting activity," Abi Khalil said. "Because it decreases platelet aggregation, aspirin is thought to lower the likelihood of forming harmful blood clots like those responsible for heart attacks and strokes."

Abi Khalil said patients should speak with their doctors to assess the benefits and risks of taking aspirin.

The research is limited in that it was based on a retrospective analysis of health records, rather than a randomized controlled trial. Further studies would help to confirm the findings, further elucidate the risks and benefits of aspirin use in this patient population, and potentially inform specific guidelines for treatment of patients with diabetes and heart failure.

The study was funded by the biomedical research program at Weill Cornell Medicine-Qatar, a program supported by Qatar Foundation.

Abi Khalil will present the study, "Primary Prevention with Aspirin Reduces Mortality in Type 2 Diabetes and Heart Failure: Results from the THIN Primary Care Database," on Sunday, March 11 at 9:45 a.m. ET in Poster Hall A/B.

The ACC's Annual Scientific Session, which will take place March 10-12 in Orlando, brings together cardiologists and cardiovascular specialists from around the world to share the newest discoveries in treatment and prevention. Follow @ACCinTouch, @ACCMediaCenter and #ACC18 for the latest news from the meeting.

Aspirin appears to reduce risk of death, hospitalization for people with heart failure and diabetes

Low-cost drug could prevent postpartum hemorrhage after normal delivery

In continuation of Tranexamic acid (TXA)

Postpartum hemorrhage (major blood loss after labor and birth) is the leading cause of maternal mortality worldwide, accounting for approximately one-quarter of all maternal deaths. In a study to be presented at the Society for Maternal-Fetal Medicine's (SMFM) annual meeting, The Pregnancy Meeting™, researchers will unveil findings that demonstrate that tranexamic acid prevents blood loss after vaginal births and postpartum hemorrhage (PPH) among women who have an operative vaginal delivery (use of a vacuum or forceps) or an episiotomy. In the United States, about 3.1% of births occur via operative vaginal delivery and 11-12% of births include an episiotomy. These rates, however, vary between low, middle and high-income countries.

Tranexamic acid (TXA) has long been used to reduce bleeding in elective surgeries, trauma patients, and menstrual blood loss. More recently, TXA has been recommended for the treatment of PPH and studied for use following cesarean birth. However, until now, there were no methodically sound studies that demonstrated TXA could prevent PPH in vaginal births. The research presented today is part of the "TRAnexamic Acid for Preventing Postpartum Hemorrhage after Vaginal Delivery," more commonly referred to as the TRAAP Trial.

In multicenter, randomized control study in France, researchers gave nearly 4,000 women in labor either one gram of TXA or a placebo. In the group that received the TXA, there was a reduction in the incidence of postpartum blood loss. In sub-group analysis, the researchers found that TXA reduced PPH in women with instrumental vaginal delivery and episiotomy. Further, there was no increase in severe adverse events in the TXA group, including thrombotic events, as compared to the placebo group in the three months after delivery.

"TXA should be considered for women who deliver via operative vaginal delivery and episiotomy in conjunction with prophylactic oxytocin," said Loïc Sentilles, MD, PhD, lead author of the study and chair of the Department of Obstetrics and Gynecology at Bordeaux University Hospital. "At the dosage studied, the only side effect observed was an increase in nausea and vomiting."

There are certain risk factors that increase the likelihood of a woman experiencing PPH, including obesity, prolonged or augmented labor, previous cesarean birth, and others. However, more women with PPH have no identifiable risk factors. Therefore, it is therefore essential to prevent PPH and ultimately save women's lives

Low-cost drug could prevent postpartum hemorrhage after vaginal delivery

Soy milk found to be most nutritious among various types of plant-based milk

In continuation of my update on soy millk,

How healthy is your almond milk really? It may taste good and may not cause you any of the unpleasant reactions caused by cow's milk. But though plant-based milk beverages of this kind have been on the market for a couple of decades and are advertised as being healthy and wholesome for those who are lactose-intolerant, little research has been done to compare the benefits and drawbacks of the various kinds of plant-based milk. 

A new study from McGill University looks at the four most-commonly consumed types of milk beverages from plant sources around the world - almond milk, soy milk, rice milk and coconut milk - and compares their nutritional values with those of cow's milk. After cow's milk, which is still the most nutritious, soy milk comes out a clear winner.

The researchers compared the unsweetened versions of the various plant-based milks in all cases and the figures below are based on a 240 ml serving.

Soy milk - the most balanced nutritional profile

• Soy milk is widely consumed for its health benefits linked to the anti-carcinogenic properties of phytonutrients present in the milk known as isoflavones.

• Has been a substitute for cow's milk for 4 decades.

• Concerns, however, are the 'beany flavor' and the presence of anti-nutrients (substances that reduce nutrient intake and digestion).

• Lactose free and can act as an alternative for patients with allergy issues caused by soybeans and almonds.

• Concerns, apart from the high carbohydrate count, is that consumption of rice milk without proper care can result in malnutrition, especially in infants.

• Widely consumed in Asia and South America

• Consumption can help reduce levels of harmful low-density lipoproteins (bad cholesterol) that are associated with cardiovascular diseases.

• Nutritional values are reduced if stored for over 2 months.

• Almonds have a high content of monounsaturated fatty acids (MUFA) that are considered helpful in weight loss and weight management. MUFA also helps in reduction of low-density lipoprotein (bad cholesterol).

• A wholesome, complete food, providing all major nutrients like fat, carbohydrates and proteins.

• Can help humans by providing a wide range of host-defence proteins because various beneficial anti-microbial effects are found in both human and bovine milks. (E.g., a study shows that in the case of infants, consumption of cow's milk has considerably reduced risk of fever and respiratory infections.)

• But the presence of various pathogens like Salmonella spp and Escherichia coli O157:H7 in milk have been associated with disease outbreaks around the world.

• One of the most common allergies among infants and children affecting 2.2-3.5% of children (a greater percentage than those who are affected by peanuts and tree nut allergies). As many as 35 % of these infants outgrow being allergic to milk by the age of 5-6, and this may increase to 80% by age 16.

• Lactose intolerance, due to the absence or deficiency of the enzyme lactase in the digestive tract, affects somewhere between 15-75 % of all adults depending on race, food habits and gut health.

• Some studies have suggested that 80 % of people of African origin and 100 % of those of Asian and Indigenous American origin are lactose intolerant.

Rice milk - sweet taste and relatively little nutrition

Coconut milk - no protein and few calories, but most of them from fat

Almond milk - need for complementary sources of food to provide essential nutrients

Cow's milk benefits & drawbacks

Cow's milk allergy & lactose intolerance

The researchers add that more work will need to be done to understand the effects of various conventional and novel processing methods on the nutritional profile, flavour and texture of these alternative milks.

Ref : https://www.mcgill.ca/newsroom/fr/node/32895

Soy milk found to be most nutritious among various types of plant-based milk

One hundred percent fruit juice does not alter blood sugar levels

The results are consistent with prior studies which have shown that consumption of 100% fruit juice is not linked to increasing risk of developing type 2 diabetes. It also supports a growing body of evidence that fruit juice has no significant impact on glycemic control.

The study involved comprehensive data analysis that quantitatively evaluated the correlation between consumption of 100% juice and blood glucose control.

The systematic review involved a meta-analysis of 18 randomized controlled trials (RCT) and assessed the effect that 100% juice from fruits like apple, citrus, berry, pomegranate, and grape, has on fasting blood insulin and blood glucose levels. This was used as a biomarker for diabetes risk.

According to The American Diabetes Association, more than 90% of the 29 million cases in adults and children in the United States fall in the category of type 2 diabetes—a metabolic disorder where the body is incapable of responding to insulin.

Following a healthy lifestyle is the first line of defense for preventing and treating type 2 diabetes. A healthy diet, regular physical exercise, and maintaining a healthy weight are also encouraged.

The US Dietary Guidelines state that  a healthy eating pattern should  include vegetables, fruits, low-fat or fat-free dairy, grains, and a variety of protein foods. A 4-oz. glass of 100% fruit juice could replace one serving (1/2 cup) of fruit, and can supplement whole fruit to help people add more nutrition to their diets.

Ref : https://www.eurekalert.org/pub_releases/2018-01/kc-n-nrf011718.php

One hundred percent fruit juice does not alter blood sugar levels

Researchers test new anti-malaria medication

In continuation of my update on Fosmidomycin

Fosmidomycin  Piperaquine

An international research team has conducted successful phase II clinical tests of a new anti-malaria medication. The treatment led to a cure in 83 cases. The new combination of drugs was developed by Professor Peter Kremsner of the Tübingen Institute of Tropical Medicine and the company DMG Deutschen Malaria GmbH. The study was recently published in Clinical Infectious Diseases and is freely accessible.

In the study, the researchers tested the efficacy, tolerability and safety of a combination of the drugs Fosmidomycin and Piperaquine. The twofold medication was administered for three days to patients aged one to thirty who were infected with malaria via the Plasmodium falciparum pathogen. In the 83 evaluable cases, there was a 100% cure rate. Patients tolerated the treatment well, and it led to a swift reduction of clinical symptoms. Safety issues were limited to changes in electrocardiogram readings, as had been described for Piperaquine.

The study was conducted at the Centre de Recherches Médicales de Lambaréné (CERMEL) in the African country of Gabon; CERMEL has close ties with the University of Tübingen. Financial support came from the nonprofit organization Medicines for Malaria Venture (MMV).

"This study represents a milestone in the clinical research into Fosmidomycin," says Tübingen Professor of Tropical Medicine Peter Kremsner. The substance was originally extracted from Streptomyces lavendulae and today can be produced synthetically. It blocks a metabolic pathway for the production of Isoprenoid in the malaria pathogen. This makes the malaria pathogen unable to metabolize or reproduce. Because Isoprenoids are formed via a different synthesis path in the human body, humans have no target structures for Fosmidomycin. For this reason humans tolerate the drug well and suffer barely any side effects. In addition, this unique mechanism excludes the possibility of cross-resistance to the drugs used in earlier malaria treatments.

The new combination meets WHO guidelines for combination therapies. The two drugs mechanisms against differing target structures means that they attack the parasite in the bloodstream independently of one another. This meets WHO requirements for a fast and effective treatment of the acute phase of infection, and for protection against relapse due to reappearance of the infection. The researchers say the effective mechanism helps to delay the formation of a possible resistance. Further studies are in planning to optimize dose.

Ref : https://www.uni-tuebingen.de/en/newsfullview-landingpage/article/vielversprechender-malaria-wirkstoff-erprobt.html

Researchers test new anti-malaria medication

FDA grants approval for first drug to treat inherited breast cancer

In continuation of my update on olaparib

The U.S. Food and Drug Administration  expanded the approved use of Lynparza (olaparib tablets) to include the treatment of patients with certain types of breast cancer that have spread (metastasized) and whose tumors have a specific inherited (germline) genetic mutation, making it the first drug in its class (PARP inhibitor) approved to treat breast cancer, and it is the first time any drug has been approved to treat certain patients with metastatic breast cancer who have a "BRCA" gene mutation. Patients are selected for treatment with Lynparza based on an FDA-approved genetic test, called the BRACAnalysis CDx.

"This class of drugs has been used to treat advanced, BRCA-mutated ovarian cancer and has now shown efficacy in treating certain types of BRCA-mutated breast cancer," said Richard Pazdur, M.D., director of the FDA's Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research. "This approval demonstrates the current paradigm of developing drugs that target the underlying genetic causes of a cancer, often across cancer types."

Breast cancer is the most common form of cancer in the United States. The National Cancer Institute at the National Institutes of Health estimates approximately 252,710 women will be diagnosed with breast cancer this year, and 40,610 will die of the disease. Approximately 20-25 percent of patients with hereditary breast cancers and 5-10 percent of patients with any type of breast cancer have a BRCA mutation. BRCA genes are involved with repairing damaged DNA and normally work to prevent tumor development. However, mutations of these genes may lead to certain cancers, including breast cancers.

Lynparza is a PARP (poly ADP-ribose polymerase) inhibitor that blocks an enzyme involved in repairing damaged DNA. By blocking this enzyme, DNA inside the cancerous cells with damaged BRCA genes may be less likely to be repaired, leading to cell death and possibly a slow-down or stoppage of tumor growth. Lynparza was first approved by the FDA in 2014 to treat certain patients with ovarian cancer and is now indicated for the treatment of patients with germline breast cancer susceptibility gene (BRCA) mutated, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer, who have been previously treated with chemotherapy. Patients with hormone receptor (HR)-positive breast cancer should have been treated with a prior hormonal (endocrine) therapy or be considered inappropriate for endocrine treatment.

FDA also expanded the approval of the BRACAnalysis CDx, an approved companion diagnostic to Lynparza, to include the detection of BRCA mutations in blood samples from patients with breast cancer.

The safety and efficacy of Lynparza for the treatment of breast cancer was based on a randomized clinical trial of 302 patients with HER2-negative metastatic breast cancer with a germline BRCA mutation. The trial measured the length of time the tumors did not have significant growth after treatment (progression-free survival). The median progression-free survival for patients taking Lynparza was 7 months compared to 4.2 months for patients taking chemotherapy only.

Common side effects of Lynparza include low levels of red blood cells (anemia), low levels of certain white blood cells (neutropenia, leukopenia), nausea, fatigue, vomiting, common cold (nasopharyngitis), respiratory tract infection, influenza, diarrhea, joint pain (arthralgia/myalgia), unusual taste sensation (dysgeusia), headache, indigestion (dyspepsia), decreased appetite, constipation and inflammation and sores in the mouth (stomatitis).

Severe side effects of Lynparza include development of certain blood or bone marrow cancers (myelodysplastic syndrome/acute myeloid leukemia) and inflammation in the lungs (pneumonitis). Lynparza can cause harm to a developing fetus; women should be advised of the potential risk to the fetus and to use effective contraception. Women taking Lynparza should not breastfeed as it could cause harm to a newborn baby.

This application was granted Priority Review, under which the FDA's goal is to take action on an application within 6 months where the agency determines that the drug, if approved, would significantly improve the safety or effectiveness of treating, diagnosing or preventing a serious condition.

Lynparza is also approved for the treatment of patients with BRCA-mutated, advanced ovarian cancer who have received three or more treatments of chemotherapy, and for the maintenance treatment of patients with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer whose tumors have completely or partially responded to chemotherapy.

Ref : https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm592347.htm

FDA grants approval for first drug to treat inherited breast cancer

Pfizer Announces FDA Approval of Xeljanz (tofacitinib) and Xeljanz XR for the Treatment of Active Psoriatic Arthritis

In continuation of my update on tofacitinib 

Pfizer Inc.  announced that the United States Food and Drug Administration (FDA) has approved Xeljanz 5 mg twice daily (BID) and Xeljanz XR (tofacitinib) extended release 11 mg once daily (QD) for the treatment of adult patients with active psoriatic arthritis (PsA) who have had an inadequate response or intolerance to methotrexate or other disease-modifying antirheumatic drugs (DMARDs). Xeljanz/Xeljanz XR is the first and only Janus kinase (JAK) inhibitor approved by the FDA for both moderate to severe rheumatoid arthritis (RA) and active PsA.

“Psoriatic arthritis is a complex and progressive disease with an unpredictable course,” said Angela Hwang, Global President, Inflammation and Immunology, Pfizer. “The approval of Xeljanz is an important step forward for patients seeking new treatments and is a testament to Pfizer’s unwavering commitment to advancing patient care.”

The recommended dose of Xeljanz/Xeljanz XR is in combination with nonbiologic DMARDs, and use in combination with biologic DMARDs or with potent immunosuppressants such as azathioprine and cyclosporine is not recommended.

The FDA approval of Xeljanz for the treatment of adult patients with active PsA was based on data from the Phase 3 Oral Psoriatic Arthritis Trial (OPAL) clinical development program, which consisted of two pivotal studies, OPAL Broaden and OPAL Beyond, as well as available data from an ongoing long-term extension trial, OPAL Balance. The findings from OPAL Broaden and OPAL Beyond were published in October 2017 in the New England Journal of Medicine.

Both pivotal studies met their two primary efficacy endpoints, demonstrating statistically significant improvements in American College of Rheumatology 20 (ACR20) response and change from baseline in the Health Assessment Questionnaire–Disability Index (HAQ-DI) score at three months in patients receiving Xeljanz 5 mg BID treatment in combination with a nonbiologic DMARD, compared to those treated with placebo. In OPAL Broaden, 50% of patients taking Xeljanz 5 mg BID achieved an ACR20 response, compared to 33% of patients taking placebo (p≤0.05), at three months. In OPAL Beyond, 50% of patients achieved an ACR20 response with Xeljanz 5 mg BID, compared to 24% of patients taking placebo (p≤0.05), at three months. In both studies, statistically significant improvements in ACR20 response was also seen with Xeljanz 5 mg BID compared to placebo at week 2, a secondary endpoint and the first post-baseline assessment (OPAL Broaden: 22% and 6% [p=0.0003], respectively; OPAL Beyond: 27% and 13% [p=0.0046], respectively).

“As a practicing rheumatologist, I’ve seen the significant physical impact psoriatic arthritis has on people living with the disease, and many patients are looking for additional therapeutic options,” said Philip Mease, M.D., Swedish Medical Center, University of Washington and study investigator. “I’m pleased that Xeljanz is now available for use in the treatment of this chronic condition.”

The safety profile observed in patients with active psoriatic arthritis treated with Xeljanz was consistent with the safety profile observed in rheumatoid arthritis patients. The most common adverse events observed occurring in greater than 3% of patients on Xeljanz 5 mg BID were nasopharyngitis, upper respiratory tract infection, headache and diarrhea.

“Psoriatic arthritis is a serious and debilitating chronic illness that should be diagnosed and treated early,” said Randy Beranek, president and CEO, National Psoriasis Foundation. “As an organization that advocates for people living with psoriatic arthritis, we welcome the availability of new therapies for treating this disease.”

Pfizer Announces FDA Approval of Xeljanz (tofacitinib) and Xeljanz XR for the Treatment of Active Psoriatic Arthritis

Diabetes drug holds promise of being developed into new treatment for Alzheimer's

A drug developed for diabetes could be used to treat Alzheimer's after scientists found it "significantly reversed memory loss" in mice through a triple method of action.

The research, published in Brain Research, could bring substantial improvements in the treatment of Alzheimer's disease through the use of a drug originally created to treat type 2 diabetes.

Lead researcher Professor Christian Holscher of Lancaster University in the UK said the novel treatment "holds clear promise of being developed into a new treatment for chronic neurodegenerative disorders such as Alzheimer's disease."

Alzheimer's disease is the most common cause of dementia and the numbers are expected to rise to two million people in the UK by 2051 according to Alzheimer's Society, who part- funded the research.

Dr Doug Brown, Director of Research and Development at Alzheimer's Society, said: ""With no new treatments in nearly 15 years, we need to find new ways of tackling Alzheimer's. It's imperative that we explore whether drugs developed to treat other conditions can benefit people with Alzheimer's and other forms of dementia. This approach to research could make it much quicker to get promising new drugs to the people who need them."

Although the benefits of these 'triple agonist' drugs have so far only been found in mice, other studies with existing diabetes drugs such as liraglutide have shown real promise for people with Alzheimer's, so further development of this work is crucial."

This is the first time that a triple receptor drug has been used which acts in multiple ways to protect the brain from degeneration. It combines GLP-1, GIP and Glucagon which are all growth factors. Problems with growth factor signaling have been shown to be impaired in the brains of Alzheimer's patients.

The study used APP/PS1 mice, which are transgenic mice that express human mutated genes that cause Alzheimer's. Those genes have been found in people who have a form of Alzheimer's that can be inherited. Aged transgenic mice in the advanced stages of neurodegeneration were treated.

In a maze test, learning and memory formation were much improved by the drug which also:-

• enhanced levels of a brain growth factor which protects nerve cell functioning
• reduced the amount of amyloid plaques in the brain linked with Alzheimer's
• reduced both chronic inflammation and oxidative stress
• slowed down the rate of nerve cell loss

Professor Holscher said: "These very promising outcomes demonstrate the efficacy of these novel multiple receptor drugs that originally were developed to treat type 2 diabetes but have shown consistent neuro- protective effects in several studies."

"Clinical studies with an older version of this drug type already showed very promising results in people with Alzheimer's disease or with mood disorders"

"Here we show that a novel triple receptor drug shows promise as a potential treatment for Alzheimer's but further dose-response tests and direct comparisons with other drugs have to be conducted in order to evaluate if this new drugs is superior to previous ones."

Type 2 diabetes is a risk factor for Alzheimer's and has been implicated in the progression of the disease. Impaired insulin has been linked to cerebral degenerative processes in type 2 diabetes and Alzheimer's disease. Insulin desensitisation has also been observed in the Alzheimer's disease brain. The desensitisation could play a role in the development of neurodegenerative disorders as insulin is a growth factor with neuroprotective properties.

Ref : http://www.research.lancs.ac.uk/portal/en/publications/-(ccd64550-72ab-4d4b-9e42-986da99f7b36).html

Diabetes drug holds promise of being developed into new treatment for Alzheimer's