A promising clinical trial developed a novel immunotherapy for lung cancer

A recent clinical trial of lung cancer has shown promising results, which could be considered as groundbreaking developments. In this clinical trial, a novel immunotherapy combination was very effective in controlling the progression and development of lung cancer. The results of this innovative study were published in the journal The Lancet Oncology. The clinical trial focused on combating non-small cell lung cancer, which is the most common form of lung cancer.

This clinical trial was conducted under the supervision of John Wrangle, M.D. He is a prominent immunologist at the Hollings Cancer Center, which is affiliated to the Medical University of South Carolina. According to Dr. John Wrangle, the clinical trial’s results are promising enough to confirm that the novel therapy can be delivered effectively in an outpatient setting.

In general, metastatic lung cancer is “incurable” in patients till date. But the results of immunotherapy have been promising enough to offer a ray of hope to these patients. . The disease-free survival rate of these patients was drastically improved when they treated with novel immunotherapy.

In the very least of terms, metastatic lung cancer patients cannot be “cured” presently but this novel immunotherapy has certainly increased their chances of survival. .Dr. John Wrangle designed this clinical trial with the help of his colleague Mark Rubinstein, Ph.D. John Wrangle and Mark Rubinstein work together at the Hollings Cancer Center. The clinical trial was started in the year 2016.

Despite receiving chemotherapy at regular intervals, metastatic non-small cell lung cancer always shows signs of progression in most patients. Therefore, these patients are also treated with immunotherapy to combat their deteriorating situation.

Immunotherapy is a recent development in cancer treatment. The principle of immunotherapy is as follows: the immune system of the human body is programmed to fight cancer cells. “Checkpoint inhibitor” is the most common class of immunotherapeutic drugs: white blood cells constitute the most important component of natural defenses in the human body.

White blood cells can effectively target cancer cells when “checkpoint inhibitor drugs” target the checkpoints associated with the regulation of immune system. According to Rubinsetin, the pathophysiology of checkpoint inhibitor drugs is as follows: the drugs cut off the brake cables of white blood cells, which are very effective in killing cancerous cells.

Tumor cells also have their own mechanism for proliferation and progression: Suppressive factors are produced by tumor cells, turning the brakes of white blood cells and preventing them from effecting the apoptosis of tumor cells.

Rubinstein further states the novel immunotherapy is more effective in killing lung cancer cells because it is based on the following principle: apart from cutting the brakes cables of white blood cells, the novel immunotherapy provides fuel so that cancer cells can be killed very effectively.

The novel immunotherapy developed by Wrangle and Rubinstein was based on the following principle: the checkpoint drug nivolumab was combined with ALT-803, which is a novel and powerful drug for stimulating the immune system.

The clinical trial was path-breaking because although the drugs were completely different from each other, they were effectively combined and administered to humans for the first time. Moreover, the results of the clinical trial indicate that these drugs can be administered safely. The evidence is compelling enough to prove that this immunotherapy can also be successful on patients who did not respond well to checkpoint therapy.

Rubinstein and Wrangle reiterate the significance of this novel immunotherapy: checkpoint therapy is not provided to lung cancer patients when they stop responding positively; however, the survival period of these patients can be improved significantly with the addition of ALT-803 drug.

This is because many studies have established that the immune system in the human body is activated by ALT-803 drug. Consequently, the lymphocytes of the immune system may be effectively coaxed to combat tumor cells. In such a scenario, combination treatments may be good enough provided they include the drug ALT-803.

In their clinical trial, they had carefully monitored the condition of 21 patients with metastatic lung cancer. Out of them, 9 patients had become resistant to single-agent immunotherapy after a certain period of time. All the nine patients either had stable disease or they responded partially to the single-agent immunotherapy. Therefore, novel combination therapy is the right step in combating cancer.

Surgery, chemotherapy, and radiation are the conventional modes of treating cancer since several decades. However, the last decade has shown prominent strides in cancer treatment, with promising results shown by targeted therapy and immunotherapy. The balance of power between cancer and human immune system has been tilted with these innovative approaches.

Better patient care with new online tool launched by FDA

The Food and Drug Administration (FDA) is the regulatory body for pharmaceutical and healthcare industry in the USA. The FDA has developed a new strategy to get real-time information and updates pertaining to the manufacture, sale, and approval of novel antibiotics and anti-fungal medications. This information shall be available to all healthcare providers (doctors, nurses, and pharmacists). The main objective of FDA is to combat the growing menace of antimicrobial resistance.

The regulatory authority FDA has created a special website that provides real-time information about how a special drug can be used to combat specific bacterial or fungal infections. This information is necessary to tackle the growing menace of medical negligence and non-optimized medications; the implications of these limitations have burdened the current healthcare system by more than billion dollars annually. The proliferation of resistant bacteria can be effectively tackled by healthcare professionals with this real-time information, thereby providing better patient outcomes.

One of the biggest problems of modern medications is the growing resistance to antibiotics. While concerted efforts are being made to develop new therapeutic drugs for various ailments, the use of antibiotics cannot be halted at this stage; however, medical doctors now prescribe limited doses of antibiotics to livestock as the problem of antimicrobial resistance is more severe in these subjects. The FDA has also implemented new guidelines on antibiotic use to improve patience care.

In a candid interview with Scott Gottlieb, M.D (erstwhile FDA Commissioner), we received the following feedback: most doctors have to tackle patients with critical ailments. To cure such patients, the doctor has to exactly identify the pathogen that is causing critical ailment in the patient. Moreover, the doctor has to assess comprehensively how defiant is the pathogen to various treatments.

A general diagnosis means that a doctor may prescribe a medication that is combated and resisted strongly by the bacterial or fungal pathogen. Such a situation does not do any good to improve the patients’ condition, and we cannot ignore the broader consequences of such situations as they can metamorphose into public health problems.

Under conventional treatment modality, the individual’s drug labeling had to be combined with the results of susceptibility testing; the process was quite lengthy and took a battery of tests for identification and confirmation.

A more centralized approach to tackle this issue of poor diagnosis and prognosis, FDA authorities have come up with a more centralized approach. The process had improved tremendously with this new tool; the efficiency of accurate diagnosis and prognosis has increased remarkably as healthcare providers are abreast with real-time information about latest drugs and medications.

In order to identify an antibacterial or antifungal drug that is most effective to treat infection in a patient, the FDA authorities have compulsorily asked physicians to perform antimicrobial susceptibility test (AST). The results of AST tests must be considered before prescribing any drug.

The criteria for these tests are as follows: “breakpoints” or “susceptibility test interpretive criteria. With these criteria, a physician has to evaluate the susceptibility of antibacterial/antifungal drugs to specific bacteria or fungi. The number of bacteria and fungi changes in the patients’ body over a period. With this changing trend, their susceptibility also decreases with respect to certain drugs. Breakpoints should be updated to take into account these occurrences.

The erstwhile conventional approach was as follows: the new breakpoint information was provided by the manufacturer of each drug in the drug label; each of these drug labels was reviewed and introduced into the market only after receiving approval from FDA. This process had to be accurately on a case-by-case basis. After receiving approval for revised drug labeling, the AST results also had to be updated and incorporated in the drug labeling. Owing to this process, there was an unnecessary delay in disseminating information to healthcare providers. In each case, the drug and device labeling had to be changed whenever there was a sharp change in breakpoints.

Because the US Congress updated the 21st Century Cure Act, the FDA could come up with this new approach: the breakpoints can now be updated for multiple drugs with same active ingredient; moreover, the information could be shared vividly through a dedicated website designed by the FDA. Thus, healthcare providers can now access all the FDA-recognized breakpoints on the online channel. Although the breakpoints are determined by the Standard-Development Organization, the FDA is the final regulatory authority that reviews and leverages their work. The FDA agrees as to whether they are appropriate for commercial use. Based on the review provided by the FDA, the standard can be accepted partially or completely. Furthermore, alternative breakthroughs can be established with the review of FDA. If companies disagree strongly with any of the recognized standards, they have full authority to supply data that can authenticate alternative breakpoints.

The breakpoint information is presented on the webpage of FDA. All drug manufacturers now have to update each drug labeling with respect to the breaking information updates. As the process has shifted, it has become automated and the previous time-consuming process of continuous updates has been overthrown. In other words, the process of drug and device labeling has become more efficient and less time-consuming. Thus, the responsibility of drug manufacturers and AST device developers has also reduced tremendously.

 

Daily doses of ibuprofen can prevent the onset of Alzheimer’s disease: Canadian neuroscientists

Research studies have been conducted by a team of neuroscientists to understand how the onset of Alzheimer’s disease can be prevented in general population. These studies were conducted under the supervision of the most famous neuroscientist in Canada, Dr. Patrick McGeer.

These comprehensive research studies were carried out a research team in Vancouver, Canada. They have presented some startling revelations: they suggest that ibuprofen [a non-steroidal anti-inflammatory drug (NSAID)] must be prescribed in daily doses at an early stage to prevent the onset of Alzheimer’s disease.

Ibuprofen is an over-the-counter medication and it seems to be a wonderful strategy to ward off this debilitating condition. According to latest estimates by the World Health Organization, Alzheimer’s disease has affected about 47 million people across the globe in 2016.

This has caused additional burden on major healthcare system all across the world, with the medical cost of treatment being pegged at US$818 billion per year. In fact, Alzheimer’s disease is considered to be the fifth most common cause of death in patients who are senior citizens (65 years and older).

According to the Alzheimer’s Association, United States of America accounts for more than 5 million cases. In fact, Alzheimer’s disease is so common in the USA that each new case is being recorded every 66 seconds. The burden on healthcare system due to Alzheimer’s disease is estimated to have been $259 billion in the year 2017. Moreover, the economic burden would certainly rise to 1.1 trillion $ by the year 2050.

The revelations of the research study are path-breaking and the fact that they have been conducted by the most noted Canadian neuroscientists (Dr. Patrick McGeer and Dr. Edith McGeer) only adds weightage to renewal of hope and prevention.

The study was conducted in the laboratory owned by Dr. Patrick McGeer and Dr. Edith McGeer (his wife). In this laboratory, they have conducted several research studies to understand the pathophysiology, prognosis, epidemiology, and prevention of several neurological diseases, with a special focus on Alzheimer’s disease.

They have devoted their careers to devise novel therapies in neurosciences for the past 30 years. The esteemed Journal of Alzheimer’s Disease has published a paper detailing the most recent discoveries of Dr. McGeer. Dr. McGeer and his team of researchers made an important announcement in 2016: they had devised a simple saliva test for the diagnosis of Alzheimer’s disease; this test could also be performed on healthy subject to predict the future onset of Alzheimer’s disease.

The saliva secretes the peptide amyloid beta protein 42 (Abeta42), whose concentration is measured by performing the aforementioned saliva test. Regardless the age and gender of healthy subjects, the rate of Abeta 42 production is almost constant. If the rate of Abeta 42 production is twice or thrice the normal rate, the individual may develop Alzheimer’s disease in the near future.

It is important to note that Abeta42 is produced throughout the body and it is relatively insoluble in bodily fluids; however, the deposits of Abeta42 occur only in the human brain. The deposited Abeta42 causes neuroinflammation to destroy the neurons of patients with Alzheimer’s disease.

Dr. McGeer and his team of neuroscientists made a path-breaking discovery in this study: they proved that Abeta42 is a peptide that is secreted into the saliva from the submandibular gland. Furthermore, they went on to prove that they could predict the susceptibility of the patient to Alzheimer’s disease by analyzing just a teaspoon of saliva.

As the saliva test is a predictive marker of Alzheimer’s disease, preventive measures can be prescribed at an early stage. This includes consumption of ibuprofen in daily doses: ibuprofen is a non-steroidal anti-inflammatory drug (NSAID).

The more startling facts of this study are as follows: the secretion of Abeta 42 peptide is same in patients and healthy individuals who are susceptible to developing the condition in the near future. What is even more assuring is the fact that elevated levels of Abeta 42 peptide are exhibited in healthy subjects at all times of the day, so the saliva test does not call for any special condition and restriction.

The saliva test can be performed on subjects at any given time of the day. In clinical practice, most patients are diagnosed with Alzheimer’s disease at the age of 65. Therefore, Dr. McGeer and his team suggest that individuals must get tested for Alzheimer’s disease at the age of 55.

The early signs of Alzheimer’s disease typically develop at the age of 55, although the subjects appear to be completely healthy in appearance. If the levels of Abeta 42 peptide are elevated at the age of 55, then a daily dose of ibuprofen is recommended for preventing the disease.

In most clinical trials, neuroscientists have included patients who showed mild to severe impairment in cognitive ability. When the disease progresses to a late stage, therapeutic opportunities are limited in number.

Unfortunately, the progression of the disease could not be halted in any of the clinical trials. The discovery of McGeer is path-breaking, innovative, and a true game changer. The saliva test is an accurate predictor of whether a healthy individual would develop Alzheimer’s disease in the near future.

They have proposed the use of ibuprofen to prevent the incidence of Alzheimer’s in such healthy individuals. Given that ibuprofen is a mild NSAID that is available over-the-counter, it is truly a simple solution that does not warrant the visit of a doctor. This is a truly innovative strategy to eliminate the crippling condition of the human brain.

 

Promising pilot trial for tumor vaccine

The University of Pennsylvania has conducted a promising clinical trial to devise a new type of vaccine for cancer. Although the clinical trial was of an initial stage, promising results have been meted out and researchers are hopeful of a breakthrough discovery.

The clinical trial was a joint collaboration between researchers of following medical schools, which are affiliated to the University of Pennsylvania: the Perelman School of Medicine and the Abramson Cancer Center. The vaccine is truly innovative in the sense that it corporates the immune cells of patients; the immune cells are directly exposed to the tumor cells of patients.

This experiment was carried out in a laboratory under simulated conditions. Following treatment, the immune cells are then injected into the patient to elicit a better immune response.This experimental clinical trial was performed on patients diagnosed with ovarian cancer at an advanced stage.

This was a pilot trial whose sole purpose was to determine the feasibility and safety of novel vaccine; however, the results were promising enough to ensure that is very effective in nature. Anti-tumor T-cell responses were elicited in more than half of the patients that participated in this clinical trial.

Patients that responded to this treatment had higher life expectancy despite tumor progression unlike patients who just did not elicit any response. In fact, one patient became “disease free” for five years after receiving being treated with this vaccine for two years. The promising results of this clinical trial have been published currently in the journal Science Translation Medicine.

The lead author of this study was Dr. Janos L. Tanyi, MD, who works as an assistant professor of obstetrics and gynecology at Penn Medicine. The researchers concluded that the novel vaccine was safe for clinical treatment of patients. This vaccine elicited a broad anti-tumor immunity; however, they have strongly recommended more clinical trials on a larger scale.

The other researchers who worked with the lead author at the Perelman School of Medicine at the University of Pennsylvania are as follows: Lana Kandalaft, PharmD, PhD, George Coukos, MD, PhD, and Alexandre Harari, PhD. The conventional treatment offered by cancer vaccines can be summarized as follows: A cell-surface receptor is a specific molecule that is mostly attacked by most cancer vaccines till date.

This molecule is generally found on cancerous cells in any kind of tumor. However, the team headed by Lausanne-Penn devised a far more aggressive approach. They developed a personalized vaccine that took into considered every individual cancer patients’ condition. For this purpose, they comprehensively analyzed the tumor system of each cancer patient.

The set of mutations are unique to each tumor, presenting a unique pathology of the impaired immune system. With this information, they developed a whole-tumor vaccine that elicited immune response and combated not just a single target in the tumor, but about hundreds or thousands. This is a truly innovative strategy that outshines the efficacy of conventional vaccines.

The basic objective of this clinical trial was to elicit a strong immune response that targets tumors comprehensively. They were successful in eliciting an immune response that hits all kinds of markers, including the markers that are unique to a particular tumor.

The formidable defenses of tumors were overcome by harnessing the T-cell immunity with the vaccine. To prepare a personalized vaccine for each patient, the researchers sifted through the mononuclear cells of peripheral blood, which was obtained from each patient.

They identified precursor cells that were suitable enough for use in this clinical experiment. These cells were grown into a culture in a laboratory under carefully controlled conditions. Thus, they produced a large number of dendritic cells. A T-cell immune response can be effectively elicited with the use of dendritic cells.

Infectious pathogens are engulfed by these T-cells; moreover, these T-cells also engulf tumor cells and anything that is considered “foreign”. Nevertheless, a specific response is elicited by the patients’ immune system when T-cells and other components of the immune system are again exposed to pieces of invader cells.

The patients’ tumor cells were obtained and a special extract was prepared from these tumor cells. Then, the extract of tumor cells was exposed to dendritic cells; the dendritic cells were activated by irradiating them with interferon gamma. Finally, the patients’ lymph nodes were injected with these activated dendritic cells and a T-cell response was generated.

The team of researchers successfully carried out this strategy on 25 patients in total. Every three weeks, each patient was administered a dose of dendritic cells; it is important to note that these dendritic cells were treated with tumor cells by a process described above.

The exposure of dendritic cells at periodic intervals was carried out for six months. A huge increase in the number of T-cells was reported in more than half of the patients included in this trial. What’s more fascinating is the fact that generated T-cells were specifically reactive to tumor cells. In other words, the personalized vaccine developed for combating cancer was hugely successful.

The patients that responded to this treatment showed 100 percent survival for a period of two years. The patients that failed to respond to this treatment showed an overall survival rate of just 25 percent over a two-year period.

In this experiment, researchers had a included a stage 4 ovarian cancer patient who was 46 years old. The prognosis of this patient is generally very poor with conventional treatment, which includes five courses of chemotherapy. Interestingly, this patient remained disease-free for five long years after receiving 28 doses of the personalized vaccine over a two year period.

In conclusion, the researchers hope that the efficacy of this personalized vaccine would be doubled if it is combined with chemotherapeutic drugs that strive to suppress anti-immune responses of the tumor.

 

 

Effects of non-optimized medications

Although the prices of drugs have risen steeply in recent times, prescription drugs are in reality much costlier than what is priced in terms of dollars and cents in retail pharmacies. A recent study was conducted by pharmaceutical researchers at the University of California in San Diego, USA.

The impact of non-optimized medications is surely dangerous: it can leads to illness and death in patients. What is frightening to know that the gruesome impact of non-optimized medications has now translated into a parallel market of $528.4 billion annually. This implies that non-optimized medications cause a 16% increase in medical expenditure in the USA, as of latest industry reports in 2016.

In the journal Annals of Pharmacology, the analysis report was published online in March 2016. The news has created a ripple effect in the pharmaceutical and healthcare sector in the USA. The research study was supervised by Dr. Jonathan Watanbe, PharmD. He is associate professor of clinical pharmacy at the Skaggs School of Pharmacy, which is affiliated to the University of San Diego in California. In an ideal situation, patients visit a doctor whenever they are sick or battling a chronic, progressive disease.

The healthcare professional prescribes medications, and patients feel better when they complete their due course of medication as per instructions. However, many a times the prescription dosage is not in agreement with the severity of your illness. This means the medication is not optimized to suit patients’ needs. Alternatively, a patient may not take the prescription drug as per indicated. In such scenarios, the patient would surely develop a adverse reaction or succumb to a new health problem.

The other collaborators in this path-breaking research study are as follows: Dr. Jan Hirsch, PhD, professor of clinical pharmacy at the Skaggs School of Pharmacy and Terry McInnis, MD of Laboratory Corporation of America. These researchers have lucidly explained the impact of non-optimized medications with a real-life scenario: Suppose a patient is down with flu and visits the emergency department of the hospital in his or her locality. A doctor would normally prescribe Tamiflu, but the patient does not take up the requisite dosage as it is too expensive.

The patients’ symptoms worsen over a period of time and he or she ultimately lands up in the Intensive Care Unit (ICU). Now, this translates into a huge financial set-back to the patient and the hospital. If the patient has been paying regular premiums to the medical insurance company, then it can certainly lead to a huge financial drain to the company. Nonetheless, the patient still has to go through a lot of paperwork to receive medical reimbursement from the company. In other words, a small problem of improper dosage and expensive medications has now snow-balled into a big problem.

The problem of non-optimized medications is not just restricted to improper dosage of medications. Watanbe has also analyzed instances where a certain medication can cause other health issues. For example, a patient is administered a steroidal drug for two years to combat epileptic fits; however, the impact of steroid is detrimental to the patients’ health.

The patient develops diabetes due to the administration of steroidal drug. Similarly, an ACE inhibitor is the most preferred drug used to combat blood pressure in patients. However, the most common side-effect of this drug is frequent cough. The patient consumes an over-the-counter medication to combat cough-and-cold and this further causes a steep rise in blood pressure. Moreover, the patient feels drowsy during daytime and ultimately falls down.

In both the scenario, a particular drug treatment used to combat a chronic ailment further leads to more complications. The researchers have developed decision-outcome models to estimate the financial impact of these situations, which includes visits to emergency department, intensive care units, additional medications, long-term medical treatment, etc.

The consequences have been shocking enough to compel changes in medical interventions: non-optimized medications certainly cause other illnesses and its annual cost is in the range of 490 to 670 billion dollars. At an individual level, the annual cost can be as high as $2500. It is important to note that this encompasses just medical treatments and does not include transportation and loss of productivity due to illness.

The last estimates were presented in the year 2008 and they seem relatively demure at $290 billion annually. Thus, the impact of non-optimized medications was just 13 percent of the US healthcare system. This implies that a phenomenal rise has occurred within a duration of eight years at 2016.

With a capitalistic economy, healthcare costs are at an all-time high; however, under the ambit of Obama healthcare, more than 20 million people were brought under the umbrella of Affordable Care Act. Thus, more than 20 million people could now access prescription drugs, a scenario that was not visible in the year 2008.

Consequently, the instance of non-adherence to prescribed dosages has increased phenomenally, leading to secondary health issues that are caused by adverse effects of long-term medication. It is not just non-adherence of medications, but also instances where healthcare professionals fail to prescribe an accurate medication region in accordance with the presented symptoms.

Each case is different, so the doctors should take into account all factors in order to provide optimized dosages to each patient rather than just considering external symptoms. For example, a diabetic patient with an attack of flu may need a more aggressive treatment regimen as compared to a healthy patient. This is because the immunity levels of diabetic patients are at an all-time low even when it is well-controlled with medications.

To overcome all these disturbing trends, Watanbe and his associates have proposed a novel model that improves patient outcomes: currently, pharmacists do not play an important role in analyzing each patients’ case. The direct contact is between the patient, nurse, and a trained medical doctor.

They have proposed a comprehensive healthcare management plan in which trained pharmacists must work along with the trained doctor to analyze the illness of each patient. This is because pharmacists are more trained in medications and their adverse effects, while a trained medical doctor is more trained in pharmacology and human body analysis.

 

 

Pancreatic stem cells can regenerate beta cells and respond to glucose

Progenitor cells within human pancreas were stimulated and developed into beta cells, which are responsive to glucose. These significant findings were published in the journal Cell Reports, which paved the way for developing regenerative cell therapies, which is an important breakthrough for type 1 diabetic patients. This addresses a major challenge that blocks the way for discovering a complete cure for type 1 diabetes.

Pancreas harbors progenitor cells and has the potential of regenerating islets. This hypothesis has been established since many decades, but it has not been proven conclusively. Scientists were able to identify the exact anatomic location of stem cells. They validated their proliferative ability to transform into beta cells, which were responsive to glucose.

An in-depth study of pancreatic stem cells was used to tap into an endogenous cell supply ‘bank’ of beta cells, which were used for regeneration purposes. In the future, these stem cells could be used for therapeutic applications of people living with type 1 diabetes.. In our previous findings, BMP-7 was used to stimulate growth and induce stem cells to transform into functional islets.

In previous studies, it was reported that bone morphogenetic protein 7 (BMP-7), which is a naturally occurring growth factor, could be used for clinical applications and to stimulate progenitor-like cells within non-endocrine pancreatic tissue of humans.

In a recent study, researchers further demonstrated that stem cells responding to BMP-7 would reside within ductal and glandular network of pancreas. Pancreatic cells are characterized by the expression of PDX1 and ALK3. The protein PDX1 is required for the development of beta cells, whereas ALK3 is a cell surface receptor associated with regeneration of multiple tissues.

With the help of “molecular fishing” techniques, researchers could selectively extract cells that expressed PDX1 and ALK3. These cells were grown in a dish, and they proliferated in the presence of BMP-7. These cells were later differentiated into beta cells. The combined results of this study were used to develop regenerative cell therapies for both type 1 and type 2 diabetes patients.

In patients with type 1 diabetes, insulin-producing cells of pancreas were destroyed by the immune system. Patients had to manage their blood glucose levels with a daily regimen of insulin therapy. In patients with type 2 diabetes, insulin was produced to some extent but beta cells became dysfunctional over a period of time.

With islet transplantation, some type 1 diabetes patients could live without insulin injections. This is because they received infusions of donor cells; however, enough cells are not there to treat millions of patients with type 1 diabetes.

Presently, research studies have primarily focused on creating more pancreatic cells, which can be transplanted from sources like embryonic (hESc), pluripotent (hPSc) and adult stem cells, and porcine (pig) islets. It would be better to regenerate insulin-producing cells in patients, which prevents the need to completely transplant donor tissue and eliminate roadblocks to other immune-related disorders.

Regenerative medicine strategies must be developed to restore insulin production in native pancreas. This would replace the need for of pancreas transplantation or other insulin-producing cells. In patients with type 1 diabetes, autoimmunity abrogation must be stopped in order to prevent the destruction of immune system and newly produced insulin cells. For this purpose, efforts were made to converge immune tolerance induction that did not require anti-rejection drugs for a long period of time.

 

Risks and benefits of phase I trials in pediatric cancer patients

On an average, one out of ten children with pediatric phase I cancer improve after being treated for the illness. But one out of fifty children succumb to drug-related complications. This was published in a systematic review and meta-analysis in PLOS Medicine. In phase I clinical trials, the safety and dosage of anti-cancer drugs was determined.

According to national and international regulations, limits on permissible risk were determined with respect to minors. Researchers systematically scoured pediatric phase I cancer studies, which were published between 2004 and 2015. They identified 170 studies that included 4,604 patients. They determined objective response rates and graded intensities as follows: 3, 4, or 5 (fatal). These caused adverse reactions of drugs.

Among all clinical trials, the overall response rate was 10.29% (95% CI 8.33 to 12.25). The overall response rate for solid tumors (3.17, 95% CI 2.62 to 3.72) was significantly greater than that for hematological malignancies (27.90, 95% CI 20.53 to 35.27).

The overall rate of fatal grade 5 adverse events was 2.09% (95% CI 1.45 to 2.72). An average response rate of 1.32 was reported for grades 3 and 4, which were drug-related adverse events per person. The adverse events and response rates were similar to those observed in adults that participated in phase I cancer trials.

This study has following limitations: heterogeneous types of cancer and treatment in included trials, reliance on only published data, and low-quality or incomplete reports of some clinical trial outcomes.

The data was coupled with careful ethical analysis, providing an empirical basis for further discussions on therapeutic status of phase I clinical trials in pediatric cancer patients. They provided evidence for refining risk/benefit in phase I trials and for identifying studies, which present greater challenges that meet standards of acceptable risk in children.

 

Correlation between obesity and gut bacteria

A new link exists between gut bacteria and obesity according to a latest research study conducted at Lund University in Sweden. In this research study, it was found that certain amino acids, which were present in our blood, were associated with both obesity and composition of gut microbiome. The significance of gut bacteria is not completely understood till date.

Many research studies have been conducted on animals, but the findings of these studies may not be applicable to human beings. Gut flora of a healthy person may not necessarily be compatible with another person.Several research studies have reported that gut microbiota plays an important role in maintaining the overall health of patients.

Gut microbiota governs the metabolism of humans, and it is linked to obesity, type 2 diabetes, and cardiovascular diseases. Previous studies have reported that the occurrence of different metabolites, i.e. small molecules or metabolic residues, varies in the bloodstream of people with these diseases.

The main aim of this new study was to identify metabolites in blood, which were linked with obesity (high body mass index, BMI). These studies had to determine whether these metabolites would affect the composition of bacterial flora in stool samples.

Researchers analyzed blood plasma and stool samples of 674 participants. They identified 19 different metabolites, which were linked with the BMI of person. There was a strong connection between obesity and following chemical compounds: glutamate and BCAA (branched-chain and aromatic amino acids).

Obesity-related metabolites were strongly linked with four different intestinal bacteria: blautia, dorea and ruminococcus in Lachnospiraceae family, and SHA98. The differences between BMI were largely associated with differences in glutamate levels and BCAA. There were interactions between metabolites and gut bacteria, but these interactions were not dependent on each other.

Glutamate is the strongest risk factor for obesity. This finding was compliant with the findings of previous studies. Moreover, BCAA predicts the onset of type 2 diabetes and cardiovascular diseases in near future.

Future studies have focused on how composition of gut bacteria could be modified, reducing the risk of obesity, metabolic diseases, and cardiovascular diseases. A proper understanding of a healthy normal gut flora is required to determine the factors that affect bacterial composition. Large population studies and intervention studies must be conducted for this purpose.

 

Calcium linked with progression of Parkinson’s disease

Excess calcium levels in brain cells lead to the formation of toxic clusters, which is a major warning sign of Parkinson’s disease. Researchers have found that calcium mediates the interaction between small membranous structures, which are present within nerve endings and are important for signaling neurons in human brain.

Alpha-synuclein is a protein associated with the development of Parkinson’s disease. When calcium or alpha-synuclein is present in excess levels, a chain reaction is triggered and it leads to the death of brain cells.

In the journal Nature, latest research studies present vividly pathogenesis of Parkinson’s disease. One in every 350 adults in the UK has Parkinson’s disease. As per global estimates, 145,000 are estimated to have developed this disease, which remains incurable till date.

Among several neurodegenerative diseases, Parkinson’s disease is the most common one that is caused under following conditions: naturally occurring proteins transform into wrongly shaped molecules, and they stick with other proteins.

They eventually form a thin structure that resembles a filament, and they are known as amyloid fibrils. Amyloid deposits of aggregated alpha-synuclein, which are also known as Lewy bodies, are warning signs of Parkinson’s disease.

The exact role of alpha-synuclein in the cell has not been understood till date. The exact role and function of alpha-synuclein is not understood till date. Alpha-synuclein is implicated in various processes, which govern smooth flow of chemical signals in human brain and flow of molecules in and out of nerve endings; however, the exact behavior of these molecules remains unclear till date.

The protein alpha-synuclein has a very small structure, and its functional capacity depends on its interaction with other proteins or structures. It is difficult to study these protein structures.

The behavior of alpha-synuclein can be determined within cells with the help of super-resolution microscopy techniques. For this purpose, researchers isolated synaptic vesicles that form a part of nerve cells, which store neurotransmitters and send signals to different nerve cells.

The release of neurotransmitters in neurons depends on the concentration of calcium levels. Calcium levels can increase in nerve cells, such as in neuronal signaling processes.

The protein alpha-synuclein would bind with synaptic vesicles at multiple points and vesicles could come into contact with each other. This indicates how alpha-synuclein is used to chemically transmit information across nerve cells.

Calcium influences the pathways of alpha-synuclein protein, which interacts with synaptic vesicles. The protein alpha-synuclein acts like a calcium sensor. In the presence of calcium, there is a change in the structure of protein alpha-synuclein and its interaction with environment. This is likely to be very important for the normal functioning of protein alpha-synuclein.

A fine balance exists between calcium and the protein alpha-synuclein in cell. Whenever there is too much of one or the other, the balance would be tipped and aggregation would begin. This leads to the development of Parkinson’s disease.

The imbalance was caused by genetically doubling the amount of alpha-synuclein, which is a protein used for duplication of genes. This is an age-related slowing mechanism involved in the breakdown of excess protein.

By increasing the level of calcium in neurons, the secretion of the protein alpha-synuclein sensitive to Parkinson’s disease can be controlled. Calcium buffering capacity is lacking in these neurons.

By understanding the role of alpha-synuclein in physiological or pathological processes, new treatments for Parkinson’s disease can be developed strategically. Calcium levels were blocked with the development of novel drug candidates, which are used in pathogenesis of heart diseases and they can also combat Parkinson’s disease.

 

The onset of type 1 diabetes may be prevented with existing drug

According to researchers at the University of Colorado, a drug used to treat high blood pressure may also be used as a preventive medication for type 1 diabetes. This study was published in the Journal of Clinical Investigation.  This seems to be an important breakthrough to combat type 1 diabetes. In the clinical investigating laboratory, this discovery was path-breaking on mice and humans with the aid of supercomputers.

In pregnant woman and children, the drug methyldopa was used to treat high blood pressure for the past 50 years. This drug was included in the list of essential drugs at the World Health Organization (WHO).

Many drugs may be used to treat a single condition; however, the path-breaking discovery was completely unrelated to current use of medication. The risk of developing type 1 diabetes increases manifold with the molecule D8, with about 60 percent people with type 1 diabetes being diagnosed with this molecule. Scientists believe that the onset of heart disease could be prevented if the molecule D8 can be blocked specifically.

Every allopathic medication has side-effects. Excessive consumption of acetaminophen can cause damage to liver. Every small molecule approved by FDA was taken into consideration and analyzed with a supercomputer to identify whether the linkage between HLA and DQ8 existed. Each drug exhibited more than thousand orientations. We identified the ones that were associated with DQ8 molecule.

Thousands of drugs were analyzed with a supercomputer. The drug methyldopa was found to block DQ8. Nevertheless, the immune function of remaining cells was not compromised in this case like the way other immunosuppressant drugs. These research studies were conducted over a period of 10 years, but the efficacy was proved in mice and in 20 patients who were diagnosed with type 1 diabetes.

These patients participated in the clinical trial that was conducted at the School of Medicine, University of Colorado. With this discovery, prediction of type 1 diabetes is possible. The ultimate aim of this study was either to delay or to prevent the onset of type 1 diabetes among the people who were at risk of developing diabetes.

The drug used to prevent type 1 diabetes can be administered orally, at least three times a day. The strategy of blocking the expression of a specific molecule can also be used to combat other diseases.This study showed significant improvement in people suffering from diabetes and other autoimmune diseases.

The same approach can also be used to treat other autoimmune disorders, such as rheumatoid arthritis, multiple sclerosis, systemic lupus, etc. To verify the implications of this disease, a larger clinical trial would be conducted at the National Institutes of Health in spring season. A very significant development would be the prevention of type 1 diabetes in people at risk of developing the illness.