Pilot Study Drug Controls Blood Sugar in People with HI | The Children's Hospital of Philadelphia

The standard treatment for some forms of congenital HI is diazoxide (right structure), a drug that controls insulin secretion by opening potassium channels in beta cells. However, this drug does not work in the most common types of HI, in which mutations prevent these potassium channels from forming.                                       

A pilot study in adolescents and adults has found that an investigational drug (Exendin 9-39) (see below structure) shows promise as the first potential medical treatment for children with the severest type of congenital hyperinsulinism, a rare but potentially devastating disease in which gene mutations cause insulin levels to become dangerously high.

Pilot Study Drug Controls Blood Sugar in People with HI | The Children's Hospital of Philadelphia

Hint of tafamidis benefit in rare polyneuropathy

The results of a randomized trial suggest that tafamidis treatment may slow the progression of early-stage V30M transthyretin familial amyloid polyneuropathy.

During 18 months of treatment, 45.3% of the 65 patients given tafamidis (see structure) 20 mg/day worsened by less than 2 points on the Neuropathy Impairment Score-Lower Limbs (NIS-LL). The rate among 63 placebo-treated patients was 29.5%, which was a nonsignificant difference. 

The Norfolk Quality of Life-Diabetic Neuropathy total score (TQOL) worsened by 2.0 points in the tafamidis group, compared with 7.2 points in the placebo group - also a nonsignificant difference.

But this analysis was based on the intent-to-treat population. A higher than anticipated dropout rate, caused by patients requiring liver transplantation, meant that just 87 of the original 125 patients actually completed the treatment.

In this group, 60.0% versus 38.1% of those treated with tafamidis and placebo had a less than 2-point deterioration on the NIS-LL, and TQOL scores worsened by a corresponding 0.1 versus 8.9..... 

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Hint of tafamidis benefit in rare polyneuropathy

Developing the First Novel Drug Regimen from TB Alliance...

TB Alliance’s push to test new drugs in combination has been done to produce a regimen that not only would be faster and easier for patients, but also would tackle two other challenges as a major step in stopping the spread of drug-resistant TB—the complexity and high cost of treatment. This promising regimen eliminates the use of injectables and projects to reduce the cost of MDR-TB therapy by as much as 90 percent.

The study, NC-001, or New Combination 1, was a two-week trial successfully completed at two centers in South Africa. It involved the new combination therapy called PaMZ, consisting of the novel TB drug candidate, PA-824 (see below structure left); moxifloxacin (right structure), an established antibiotic not yet approved for use in first-line TB therapy and being developed in partnership with Bayer Healthcare AG; and pyrazinamide, an existing TB drug.

“Treating drug-sensitive and drug-resistant TB with the same regimen can simplify the delivery of TB treatment worldwide,” said Andreas Diacon, MD, the trial’s principal investigator and lead author of the Lancet study. “The results of this study give healthcare providers on the front lines of the TB epidemic hope for better, faster tools needed to stop this disease.”

 (Pyrazinamide)

Newscenter | Global Alliance for TB Drug Development

Chemical makes blind mice see; compound holds promise for treating humans

The chemical, called AAQ (see below structure,   acrylamide- azobenzene - quaternary ammonium),  acts   by taking the remaining, normally "blind" cells in the retina  sensitive to  light,  said  lead  researcher  Richard Kramer, UC Berkeley professor of molecular and cell biology.   AAQ is a photoswitch that binds to protein ion channels on the surface of retinal cells. When switched on by light, AAQ alters the flow of ions through the channels and activates these neurons much the way rods and cones are activated by light.

The blind mice in the experiment had genetic mutations that made their rods and cones die within months of birth and inactivated other photopigments in the eye. After injecting very small amounts of AAQ into the eyes of the blind mice, Kramer and his colleagues confirmed that they had restored light sensitivity because the mice's pupils contracted in bright light, and the mice showed light avoidance, a typical rodent behavior impossible without the animals being able to see some light. Kramer is hoping to conduct more sophisticated vision tests in rodents injected with the next generation of the compound.

Because the chemical eventually wears off, it may offer a safer alternative to other experimental approaches for restoring sight, such as gene or stem cell therapies, which permanently change the retina. It is also less invasive than implanting light-sensitive electronic chips in the eye.

"The advantage of this approach is that it is a simple chemical, which means that you can change the dosage, you can use it in combination with other therapies, or you can discontinue the therapy if you don't like the results. As improved chemicals become available, you could offer them to patients. You can't do that when you surgically implant a chip or after you genetically modify somebody," Kramer said........... 

The Antidepressant Sertraline Provides a Promising Therapeutic Option for Neurotropic Cryptococcal Infections

New research conducted by biologists at Texas A&M University suggests that sertraline (see structure below, ZOLOFT®), one of the most widely prescribed antidepressants in the world, also packs a potential preventative bonus  potent mechanisms capable of inhibiting deadly fungal infections. 

C. neoformans is a potentially dangerous fungal pathogen found in many soils throughout the world that may cause systemic infections, particularly involving the central nervous system. In most cases, the microscopic, airborne fungal cells of C. neoformans cause asymptomatic colonization in the lungs. However, Lin says the fungus is particularly aggressive in people with weakened immune systems and can spread to other parts of the body, such as the brain and spinal cord, resulting in cryptococcal meningitis  a condition that, in absence of treatment, is fatal. 

Rapamycin effective in mouse model of inherited heart disease and muscular dystrophies

In continuation of my update on Rapamycin (Sirolimus)...

Rapamycin, an immunosuppressant drug used in a variety of disease indications and under study in aging research labs around the world, improved function and extended survival in mice suffering from a genetic mutation which leads to dilated cardiomyopathy (DCM) and rare muscular dystrophies in humans. There are currently no effective treatments for the diseases, which include Emery-Dreifuss muscular dystrophy and limb-girdle muscular dystrophy. The familial form of DCM often leads to sudden heart failure and death when those affected reach their 40s and 50s.

Scientists from the Buck Institute and other organizations focused on mutations in the gene LMNA, which produces A-type lamins. Mutations in this gene are associated with at least 13 diseases, with DCM among the most common. DCM accounts for 60 percent of all cardiomyopathy cases. LMNA mutations may account for up to one-third of patients that are diagnosed as having DCM and conduction disease. DCM causes a thinning of the left ventricle and loss of cardiac function. The study showed that deletion of the LMNA gene led to ramped up activity in the molecular pathway mTOR (mammalian target of rapamycin) and that treatment with rapamycin turns down the abnormal signaling. Senior author Brian K. Kennedy, PhD, President and CEO of the Buck Institute for Research on Aging, says treatment with rapamycin extended mouse lifespan by 60 percent in a relatively rapid onset model of disease.

Ref : http://stm.sciencemag.org/content/4/144/144ra103

Rapamycin effective in mouse model of inherited heart disease and muscular dystrophies

Once-daily Gralise significantly reduces pain intensity in PHN patients

Depomed, Inc. announced that a report of Phase 3 data published online this month, ahead of the print edition,  in the Clinical Journal of Pain showed that once-daily Gralise^® (gabapentin) tablets (1,800 mg) formulation significantly reduces intensity of pain in patients with postherpetic neuralgia (PHN). The results showed that patients treated with Gralise experienced a significant reduction (- 2.12) in their average daily pain intensity compared with placebo treated patients (-1.63; P=0.013). This difference from placebo was statistically significant after one week and continued to be superior through the duration of the study. 

About Gralise (below structure-Gabapentin) : Gabapentin (brand names Fanatrex, Gabarone, Gralise, Neurontin, Nupentin) is a pharmaceutical drug, specifically a GABA analogue. It was originally developed for the treatment of epilepsy, and currently is also used to relieve neuropathic pain. There are, however, concerns regarding the quality of the trials conducted.

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Depomed - Investor Relations - Press Releases

New agents, Antimicrobial peptides, join the fight against antibiotic-resistant bacteria

Line Hein-Kristensen worked with a new class of antimicrobial agents, the so-called antimicrobial peptides. Antimicrobial peptides are part of the immune system in all life forms, including humans, and constitute the first line of defence against pathogenic organisms entering the body, e.g. via the food that we eat.

Antimicrobial peptides are special in that they act differently to conventional antibiotics and may thus be active against the very bacteria that are resistant to conventional antibiotics. These also include multiresistant bacteria – for example MRSA and ESBL against which we now have only a limited arsenal of treatment options.

Synthetic compound emulating nature.........................

Novel chemical methods have now made it possible to emulate the structure of natural antimicrobial peptides and thus also to develop many novel synthetic variants. Line Hein-Kristensen's PhD project focuses specifically on a series of synthetic compounds that have been designed, synthetised and characterised the Faculty of Health and Medical Sciences, University of Copenhagen.

The findings of her research show that the degree of antimicrobial activity against a range of food-borne and nosocomial (hospital-acquired) pathogenic bacteria depends on the chemical structure of custom-designed compounds. The research also shows that the synthetic antimicrobial peptides kill the bacteria by disrupting the bacterial cell membrane.

New agents join the fight against antibiotic-resistant bacteria

Ref :  http://www.dtu.dk/upload/institutter/food/publikationer/2012/phd%20thesis,%20line%20h.%20kristensen.pdf 

Memantine, Drug Shown to Improve Memory in Those With Down Syndrome

In continuation of my update on  memantine

Costa, an associate professor of medicine, and his colleagues studied 38 adolescents and young adults with Down syndrome. Half took the drug memantine, used to treat Alzheimer's disease, and the others took a placebo.

Costa's research team hypothesized that memantine, which improved memory in mice with Down syndrome, could increase test scores of young adults with the disorder in the area of spatial and episodic memory, functions associated with the hippocampus region of the brain.

Participants underwent a 16-week course of either memantine or a placebo while scientists compared the adaptive and cognitive function of the two groups.

While they found no major difference between the groups in adaptive and most measures of cognitive ability, researchers discovered that those taking memantine showed significant improvement in verbal episodic memory. One of the lowest functioning individuals in the study saw a ten-fold increase in memory skills.

"People who took the medicine and memorized long lists of words did significantly better than those who took the placebo," said Costa, a neuroscientist specializing in Down syndrome research. "This is a first step in a longer quest to see how we can improve the quality of life for those with Down syndrome."

Translational Psychiatry - Antagonism of NMDA receptors as a potential treatment for Down syndrome: a pilot randomized controlled trial

Eliquis Receives Positive Opinion from CHMP | News | Drug Discovery and Development Magazine

In continuation of my update on Apixaban
Eliquis Receives Positive Opinion from CHMP | News | Drug Discovery and Development Magazine