Radioisotope Shortages

This is an interesting article from MedPage Today about how technetium-99 is produced and distributed for medical imaging and about how the supply is threatened by a planned reactor shut-down in 2016. Here is the link and I’ve copied the article below.


New Process Could Ease Isotope Crunch


By Michael Smith, North American Correspondent, MedPage TodayPublished: February 26, 2012

1 comment(s)


The solution to a looming shortage of the medical isotope technetium-99 may lie in the basements of many hospitals, according to Canadian scientists.

The answer: cyclotrons.

Researchers associated with Vancouver’s TRIUMF nuclear physics research center say machines that are widely used to make other imaging isotopes can be modified to make technetium-99, the substance at the heart of the isotope crisis.

The process is relatively simple to implement and can produce commercial quantities of technetium-99 at a reasonable cost, they said. Best of all, it uses equipment that is a lot cheaper than a nuclear reactor, currently needed to make the isotope.

“We don’t think there are any show-stoppers here at all,” said Tom Ruth, PhD, who is principal investigator for the two-year, $6-million project.

“We’ve demonstrated it all works and it’s feasible and within the economic realm of being competitive,” he told MedPage Today.

But there remain a few hurdles that still need to be cleared, according to Robert Atcher, PhD, of the University of New Mexico in Albuquerque, who is past president of SNM and chairman of the molecular imaging society’s isotope committee.

Among them are regulatory issues, he told MedPage Today, such as does the technetium-99 produced by the cyclotrons meet medical safety standards, and does the production process itself meet nuclear safety guidelines?

Atcher pointed out that cyclotron production may work well in the Canadian health system but he’s not convinced it’s suitable for the U.S.

Isotope Insufficiency

If one possible solution to the isotope crunch lies in Canada, the root of the problem is also there.

Canada’s aging NRU reactor in Chalk River, Ont., is the main source of technetium-99 in North America. It has been in and out of service for the past several years, and the Canadian government says it will get out of the medical isotope business entirely by 2016.

That’s a problem because technetium-99 is used in about 85% of all medical imaging procedures, and the remaining facilities that produce it — reactors in the Netherlands, Belgium, France, Australia, and South Africa — are unlikely to be able to take up the slack left by the Canadian shutdown.

The reactors don’t actually make technetium-99. Instead they make molybdenum-99, a radioactive substance that decays into technetium-99.

The molybdenum-99 is packed into “generators” and distributed to hospitals, where nuclear medicine specialists can draw off the technetium-99 as needed for about a week.

The cyclotron process is more direct, Ruth said. For between three and six hours, the machine sends a stream of high-energy protons at a target of molybdenum-100, a nonradioactive isotope of the element, converting some of its atoms to technetium-99.

At the end of that time, a half-hour chemical processing step removes technetium-99 from the target and it’s ready to be used in imaging procedures, he said. Unlike nuclear reactors, the machines that are needed are in wide use.

The downside is that the technetium-99 has a half-life of only about six hours, meaning it can’t be stored for a long time or shipped long distances, Atcher said.

In Canada, where a large fraction of the population lives in urban centers, that may not matter, he said, as a dozen cyclotrons could probably handle the country’s needs.

But in the U.S., the distance factor might mean that rural areas would be left out, Atcher said.

As well, the short half-life might make it more difficult to get technetium-99 on an emergency basis — at night, for instance, or on weekends — where specialists currently can simply draw off a little more from their generators.

“You can’t equal the convenience of the generator,” Ruth conceded. “That’s why they’ve lasted so long.”

So some generator production will probably continue, but the cyclotron process is “a piece of the puzzle,” he said.

The researchers made a point of using machines similar to those now in use. In particular, of the three machines they modified to make the substance, two were 16 MeV machines made by GE, which are in common use around the world.

At least in Canada, one of the regulatory hurdles — establishing nuclear safety — is under way, Ruth said. The Canadian Nuclear Safety Commission, the equivalent of the U.S. Nuclear Regulatory Commission, was involved in and approved the modifications to the test machines.

The second hurdle, establishing medical safety, will require clinical trials. Ruth said he and his colleagues hope to have a phase I study running this fall to show that their isotope is both safe and efficacious.

The technetium-99 they produce, he said, is identical structurally to the substance produced by molybdenum-99 generators. But the cyclotron process also introduces some other technetium isotopes — less than 1%, the researchers calculated — and those might have some unforeseen toxicity.

Ruth said Health Canada, the government department that has equivalent safety jurisdiction to that of the FDA, has also been aware of the research from the beginning.

Technetium Tussles

Another issue is cost, Atcher said. Given that the Canadian reactor is going out of business, there was pressure in Canada to find other sources of isotopes, even if they cost more.

But whether the U.S. market would pay more is another question, he said.

Ruth told MedPage Today he thinks the cost per dose will not be much higher, as least according to his group’s preliminary calculations. But complicating the picture are the subsidies that underlie the current price of technetium-99.

All of the reactors in the business, including Chalk River, are primarily research machines that get substantial support from their respective governments — in essence, a subsidy for the isotope business.

But there is currently a push to use molybdenum-99 made in reactors that use low-enriched uranium, unlike the highly enriched uranium used in current machines.

Those facilities may not get similar support, so that the cost of generators would rise, Ruth said.

The U.S. Department of Energy has been supporting efforts to develop a domestic source of isotopes. Two groups had been trying to develop a reactor-based technology, but one of those — led by General Electric — has recently dropped the project.

As well, there are two projects based in Wisconsin that do not use reactors. Madison-based NorthStar Medical Radioisotopes is hoping to have commercial production of molybdenum generators this year, while Middleton-based Phoenix Nuclear Labs is also developing a production process.

Because of that work, Atcher said he is more optimistic that the isotope market can become more stable than it has been.

“But when we have a hard deadline of 2016, you always wonder what can go wrong in terms of technical development,” he added.

Bench to Bedside

Technical development aside, it’s also important to get products from the lab to the clinic, Ruth said. His group has done the scientific spadework and is now trying to find commercial partners to make and distribute cyclotron-produced technetium-99.

Ottawa-based Nordion, the current commercial intermediary between the Chalk River reactor and the clinic, said it’s discussing the issue with TRIUMF.

In a statement, the company said it considers the cyclotron process to be something that would supplement reactor-based production.

For clinicians, Ruth said, the key question is reliability — can they depend on having enough isotope? That is a matter of how the cyclotrons are distributed and what other demands are placed on them.

For example, the machine they tested in Vancouver could probably supply the needs of the Greater Vancouver Area, with a population of about 2.1 million.

That device, at the B.C. Cancer Agency, has other functions, Ruth said, but a similar machine dedicated to making technetium-99 could probably serve all of the people in the province, some 3.5 million.

Similar calculations would have to be made anywhere the process is used, he said.

On the other hand, clinicians are used to some isotopes with a short half-life, such as fluorine-18, so that the distribution channels should not be a major issue.

“We think we’ve dotted all the i’s and crossed all the t’s,” he said.

But “time will tell,” Atcher noted.

Pancreatic neuropeptide Y in neuropsychiatry

This abstract outlines a gradual development of evidence for the effects of neuropeptide Y in mood and anxiety disorders.

Expert Opin Ther Targets. 2011 Nov;15(11):1317-31.

Central functions of neuropeptide Y in mood and anxiety disorders.


Karolinska Institutet-Clinical Neuroscience, Stockholm, Sweden.


INTRODUCTION: Neuropeptide Y (NPY) is a highly conserved neuropeptide belonging to the pancreatic polypeptide family. Its potential role in the etiology and pathophysiology of mood and anxiety disorders has been extensively studied. NPY also has effects on feeding behavior, ethanol intake, sleep regulation, tissue growth and remodeling. Findings from animal studies have delineated the physiological and behavioral effects mediated by specific NPY receptor subtypes, of which Y1 and Y2 are the best understood. AREAS COVERED: Physiological roles and alterations of the NPYergic system in anxiety disorders, depression, posttraumatic stress disorder (PTSD), alcohol dependence and epilepsy. For each disorder, studies in animal models and human investigations are outlined and discussed, focusing on behavior, neurophysiology, genetics and potential for novel treatment targets. EXPERT OPINION: The wide implications of NPY in psychiatric disorders such as depression and PTSD make the NPYergic system a promising target for the development of novel therapeutic interventions. These include intranasal NPY administration, currently under study, and the development of agonists and antagonists targeting NPY receptors. Therefore, we are proposing that via this mode of administration, NPY might exert CNS therapeutic actions without untoward systemic effects. Future work will show if this is a feasible approach.

[PubMed - indexed for MEDLINE]

Neuroprotection in Neurodegenerative Diseases

This abstract outlines preliminary work in identifying first-line FDA-approved neuropsychiatric medications that may also work to slow progression of an assortment of neurodegenerative diseases.

J Neuropsychiatry Clin Neurosci. 2011 Summer;23(3):242-60.
Psychopharmacological neuroprotection in neurodegenerative diseases, part III: criteria-based assessment: a report of the ANPA committee on research.
Lauterbach EC, Mendez MF.
SourceDepartment of Psychiatry, Neurology Section, Mercer University School of Medicine, Macon, GA, USA.

Neuroprotective therapies for neurodegenerative diseases (NDDs) have proven elusive. The established psychotropic agents commonly used to treat the neuropsychiatric manifestations of NDDs are potential neuroprotective therapies, and neuropsychiatrists and others may benefit from a knowledge of the neuroprotective properties of these medications. This report identifies FDA-approved, first-line psychotropic drugs affecting intracellular mechanisms and meriting disease-modifying clinical trials in NDDs. The authors evaluated evidence for neuroprotection according to 1) preclinical; and 2) clinical criteria. Despite low-to-moderate preclinical evidence scores and scant clinical evidence, the most promising investigative priorities are 1) lithium and paroxetine in Alzheimer’s disease (AD); 2) lithium in tauopathies (frontotemporal lobar degeneration [FTLD], FTDP-17); 3) lithium-plus-valproate in AD and amyotrophic lateral sclerosis; 4) pramipexole and valproate in Parkinson’s disease; 5) amantadine and buspirone in multiple system atrophy; and 6) antidepressants in Huntington’s disease. Preliminary clinical results signal caution regarding olanzapine use in AD and poor tolerability of lithium in progressive supranuclear palsy and corticobasal degeneration. These preliminary findings can lead to further clinical drug trials on the use of these well-known medications, not only for their psychotropic effects, but also for neuroprotection in NDDs.

PMID:21948886[PubMed - indexed for MEDLINE]

Detecting Lung Cancer by Breath Sampling

This trade press article reports briefly on an approach to identifying the presence of lung cancer through analyzing chemical constituents in breath and comparing them with known spectrum samples of normal and already diagnosed patients. Here is the link. Still in development, this is reminiscent of another article that I recently saw about training giant African rats to detect tuberculosis by sniffing the sputum of potentially infected patients.

20111227 Detecting Lung Cancer by Breath_111223091331

Web address:

New Sensor to Detect Lung Cancer from Exhaled Breath

Tecnalia, through the Interreg project Medisen, is contributing to develop biosensors capable of detecting the presence of tumour markers of lung cancer in exhaled breath. (Credit: Image courtesy of Elhuyar Fundazioa)

ScienceDaily (Dec. 23, 2011) — Tecnalia, through the Interreg project Medisen, is contributing to develop biosensors capable of detecting the presence of tumour markers of lung cancer in exhaled breath. This is possible because of the changes produced within the organism of an ill person, changes reflected in the exhaled breath of the patient and which enable determining the presence of this type of marker during the initial stages of the disease.


Some illnesses such as lung and stomach cancer or liver diseases which, due to the difficulty of diagnosis, have symptoms that are often confused with routine disorders. Therefore, in most cases, the disease is only detected at an advanced stage. New methods for early detection are being investigated as an urgent need.

Tecnalia, through the Interreg project Medisen, is contributing to develop biosensors capable of detecting the presence of tumour markers of lung cancer in exhaled breath. This is possible because of the changes produced within the organism of an ill person, changes reflected in the exhaled breath of the patient and which enable determining the presence of this type of marker during the initial stages of the disease.

Patients with lung cancer, treated in the Section of Medical Oncology of the Institute of Onco-Haemathology of the Donostia Hospital (IDOH) have collaborated in this phase of the project. For that, the Ethic Committee of the Clinical Research of Euskadi (CEIC) gave the authorization to the Instituto Biodonostia for the clinical trials

Human breath, whether from a healthy or ill person, is composed of a hundreds of organic compounds: acetone, methanol, butanol, hydrocarbons, amongst others. There is not a single specific component in the exhaled breath capable of acting as a marker for the diagnosis of lung cancer. A range of biomarkers and its combination should be selected. The compounds of interest are generally to be found at 1-20 parts per billion (ppb) in healthy human breath but can be increased 10-100-fold in the breath of sick patients. In order to be able to detect these changes the development of novel materials was required.

During the first phase of the project, breath samples were collected by the hospital staff by a breath collecting device. A detailed analysis of the most representative compounds present in the breath samples has been carried out and the family or families of compounds required to act as markers for the presence of lung cancer selected. Organic compounds have been analysed using gas chromatograph/mass spectrometry analysis (GC/MS). Then, the GC/MS results of breath tests have been analysed by statistical and structural algorithms to discriminate and identify “healthy and “cancerous” patterns that really provide information for the design of the sensor.

In parallel, novel materials for the detection of the selected organic compounds have been developed by Tecnalia in order to increase the sensitivity of the devices. Participating together with Tecnalia in this project were the Instituto de Tecnologías Químicas Emergentes de La Rioja (Inter-Química) designing the sensor device and the University of Perpignan (France) testing the novel materials.

As a conclusion, the biosensors will facilitate the diagnosis of certain diseases; mainly those located in the lungs, at the initial stages of the illness, which could increase considerably the chances of survival.Story Source:

The above story is reprinted from materials provided by Elhuyar Fundazioa.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.





Elhuyar Fundazioa. “New sensor to detect lung cancer from exhaled breath.” ScienceDaily, 23 Dec. 2011. Web. 27 Dec. 2011.

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.


How interoperable digital signatures will bring clinical trials to the cloud.

I have copied this interesting article about the technology of digital signatures adapted to the security and audit requirements of clinical trials and also placed a link here.

The Paperless, Cloud-Based Clinical Trial; It’s Happening Now

By Mollie Shields-Uehling, President and CEO,
SAFE-BioPharma Association

Interoperable digital identities are poised to help the global biopharmaceutical industry harness the full power of cloud computing. One major outcome will be more efficient and less costly clinical trials.

An ongoing study involving cancer researchers at the National Cancer Institute’s Cancer Therapy Evaluation Program (NCI/CTEP) and counterparts at Bristol-Myers Squibb and Sanofi provides a window into the future of this process.

NCI/CTEP is the world’s largest sponsor of cancer treatment clinical trials. In 2010, it generated almost 100,000 pages to get clinical trials underway.

The study eliminated paper from the clinical trial start-up process by placing documents in the cloud and giving the researchers access using their digital identity credentials. These credentials also gave the researchers the ability to apply digital signatures to the electronic documents.

As a result, dramatic time savings occurred for all document flows requiring multiple signatures or signatures from people working off-site. Because cloud-based digital signatures were used, there was an audit trail of when the document was uploaded, of the email that was sent to alert the signatory that the document was available for signature, and when the document was actually signed.

The success of the study was based on the use of digital identities that are interoperable. Interoperable digital identities also will be at the foundation of future cost and time savings in the entire clinical trial process.

By way of explanation, these identities are digital credentials that are closely linked to the user’s proven identity and installed on a computer, cell phone or other device. They become interoperable when the entities that issue them have gone through a process that assures they can be trusted by governments, in other companies and in other industries.

That’s where the SAFE-BioPharma digital identity standard plays its critical role. The standard — developed by a consortium of biopharmaceutical and related companies with participation from the US Food and Drug Administration and the European Medicines Agency – provides standardized ways to manage and verify digital identities and to apply legally binding digital signatures to electronic documents.

Unlike simple electronic signatures, SAFE-BioPharma digital signatures cryptographically guarantee the integrity of every document. And unlike some solutions that bill themselves as “digital” SAFE-BioPharma signatures are based on interoperable identities. They are trusted by government agencies and by other important collaborators outside the organization’s firewall.

This combination of factors – trust, interoperability and the ability to sign electronic documents in a legally-binding way – has made identity credentials based on the SAFE-BioPharma standard critical where used.

The NCI/Bristol-Myers Sqibb/Sanofi study started in 2010. BMS and Sanofi researchers are using SAFE-BioPharma digital identity credentials and NCI researchers are using digital identity credentials issued by the federal government. Because of their interoperability, all were able to access, sign and exchange documents using cloud computing.

As one sign of efficiency, NCI informally calculated that each digital signature used in the study saved about 2.2 hours over conventional “wet” signatures.

As the study moves to production, we are enhancing the signing application to fit into NCI processes with even greater efficiency.

I’m confident that lessons from this study will have a long range impact on the clinical trial process. Readers who are interested should download the white paper documenting its development and success (

Mollie Shield-Uehling is President and CEO of SAFE-BioPharma Association. In this role she directs the business and strategic activities of SAFE-BioPharma Association. She has more than 20 years of international trade and biopharmaceutical industry experience. She is a member of the association’s Board of Directors.

“Protectans” mitigate effects of therapeutic radiation on healthy cells.

A company called Cleveland BioLabs, now based in Buffalo, NY, has an interesting discussion of their investigational pipeline involving radiation-sparing medicines. I have included the link here and also copied the webpage below.


The scientific foundation of Cleveland BioLabs’s product development efforts is based upon proprietary discoveries of the molecular mechanisms underlying a form of cell death called apoptosis. Apoptosis is a highly specific and tightly regulated form of cell death that can be initiated by a variety of external and internal stresses including exposure to radiation or toxic chemicals. For example, exposure to high doses of radiation is lethal due to massive cell loss through apoptosis in radiosensitive tissue such as the hematopoietic (HP) system and the gastrointestinal (GI) tract (“Acute Radiation Syndrome” (ARS)). In addition, apoptotic death of bystander non-tumor cells accounts for the dose-limiting toxicity of anti-cancer radio- and chemotherapy that affects more than 70% of patients. Apoptosis is also a major determinant of tissue damage caused by acute medical conditions involving ischemia (lack of sufficient blood flow) such as cerebral stroke, heart attack and acute renal failure. On the other hand, apoptosis can serve as a protective mechanism that allows the body to rid itself of defective cells, such as those that have gained malignant potential and would develop into tumors if not eliminated. Thus, strategic manipulation of apoptosis has a wide range of potential therapeutic applications.

Based upon research by the founder and Chief Scientific Officer of CBLI, Dr. Andrei Gudkov, we have developed novel proprietary strategies to target the molecular mechanisms controlling apoptotic cell death for therapeutic gain. These strategies exploit naturally occurring differences in the way tumor cells and normal cells respond to genotoxic (DNA-damage-inducing) stresses such as radiation. As illustrated in the Figure below, tumor cells are typically characterized by defects in stress-induced apoptotic pathways. Such defects frequently include inactivation of the p53 tumor suppressor and/or constitutive activation of NF-kappaB signaling. Thus, while normal cells undergo apoptosis in response to radiation, tumor cells die through other non-apoptotic pathways.

CBLI is focused on development of two general classes of apoptosis-modulating pharmaceuticals:

1. Protectans are compounds that block stress-induced apoptosis. Since the targeted pathway is typically only functional in normal cells, Protectans have the potential to specifically protect normal, but not tumor, cells from death in the face of stress. CBLI’s lead Protectan compounds, CBLB502 and CBLB600 Series, are optimized derivatives of microbial factors that are natural regulators of apoptosis. Our expectations for these rationally designed compounds have been borne out in extensive preclinical studies showing that Protectans rescue mammals exposed to lethal doses of radiation by protecting the vulnerable HP and/or GI systems. Protectans may be useful in counteracting the effects of radiation exposure in military, terrorist attack and nuclear accident settings, in protecting cancer patients from the negative side effects of radiation and chemotherapy, and in limiting ischemia-induced tissue damage. CBLI’s recent discovery that CBLB600 Series Protectans also regulate proliferation and mobilization of hematopoietic stem cells opens up another wide array of potential applications for these drugs.
2. Curaxins are small molecules designed to reactivate apoptotic pathways in tumor cells by simultaneously restoring p53 function and inhibiting NF-kappaB activity. Curaxins induce apoptosis in a broad range of human tumor cells, yet have no effect on normal cells. Curaxins also sensitize tumor cells to the apoptosis-inducing effects of other cancer treatments. Thus, Curaxins may be useful either as a monotherapy or as an adjuvant to other therapies for a number of human malignancies including renal cell carcinoma, hormone-refractory prostate cancer, soft-tissue sarcoma and myeloma. CBLI’s first generation Curaxin, CBLC102, has demonstrated safety and activity in a Phase II clinical trial in patients with hormone-refractory prostate cancer. In addition, CBLI has successfully identified a lead next generation Curaxin compounds that have demonstrated reliable anti-tumor effects in animal models of colon, breast, renal and prostate cancers. These next generation compounds have favorable pharmacological characteristics, are suitable for oral administration and demonstrate a complete lack of genotoxicity. They share all of the positive aspects of CBLC102, but significantly exceed the former compound’s activity and efficacy in pre-clinical tumor models. Development of the next generation compounds will be conducted through Incuron, a joint venture between CBLI and BioProcess Capital Ventures. “

I haven’t had a chance to investigate the literature publication record for these compounds, but they sound novel and potentially very useful.

“Meditation keeps the mind on track.”

Here is an interesting article, one among many, on the results of science applied to the practice of meditation, from MedPage Today:

Meditation Keeps the Mind on Track

By Kristina Fiore, Staff Writer, MedPage Today

November 22, 2011

MedPage Today Action Points

Explain that this study found that meditation diminishes activity in areas of the brain associated with mind-wandering, the so-called default mode network in the medial prefrontal cortex and the posterior cingulate corticies.
Note that the study used functional MRI to assess brain activation during both a resting state and a meditation period in experienced mindfulness meditation practitioners and controls.


Meditation diminishes activity in areas of the brain associated with mind-wandering, researchers found. Compared with novice meditators, experienced study participants had significant deactivation in parts of the brain associated with the “default mode network” — areas linked with attentional lapses and anxiety, Judson Brewer, MD, of Yale University, and colleagues reported in the Proceedings of the National Academy of Sciences.

Practiced meditators also reported less mind-wandering during meditation than did their less experienced counterparts, the researchers found. Aside from attention lapses and anxiety, the “default mode network,” or DMN, has also been associated with certain conditions, including ADHD and Alzheimer’s disease. Conversely, mindfulness training has been shown to benefit certain conditions, such as pain, substance use disorders, anxiety, and depression.

So to assess whether mindfulness-based meditation can reduce activity along this brain axis, the researchers analyzed both experienced meditators and controls who’d never practiced the technique. The researchers used functional MRI to assess brain activation during both a resting state and a meditation period in 12 experienced mindfulness meditation practitioners and 13 controls.
Groups attempted three different types of meditation: concentration, loving-kindness, and choiceless awareness. Concentration is intended to prevent practitioners from engaging with their preoccupations; loving-kindness focuses on fostering acceptance; and choiceless awareness allows for focusing on whatever arises in the conscious field of awareness at any moment.

Brewer and colleagues found that experienced meditators reported less mindwandering during meditation than did controls, which was true across groups. At the same time, they generally saw less activation in the main nodes of the DMN — the medial prefrontal cortex and the posterior cingulate corticies — in experienced meditators than in controls. While there was significantly less activation in the posterior cingulate cortex/precuneus and in the superior, middle, and medial temporal gyri and uncus, the trend toward diminished activation in the medial prefrontal cortex was not significant, they noted. With regard to the specific types of meditation, the researchers found less activation in experienced meditators than in controls in the following regions:

Concentration: posterior cingulate cortex, left angular gyrus

Loving-kindness: posterior cingulate cortex, inferior parietal lobule, and inferior temporal gyrus extending into hippocampal formations, amygdala, and uncus

Choiceless awareness: superior and medial temporal gyrus

When using the posterior cingulate cortex as a seed region, the researchers saw significant differences in connectivity patterns with several other brain regions, notably the dorsal anterior cingulate cortex, for experienced meditators compared with controls. And when using the medial prefrontal cortex as the seed region, they found increased connectivity with the fusiform gyrus, the inferior temporal and parahippocampal gyri, and the left posterior insula.

These patterns held during the resting-state baseline period as well, the researchers said, suggesting that meditation practice “may transform the resting-state experience into one that resembles a meditative state, and, as such, is a more present-centered default mode.”

The researchers concluded that the overall results “support the hypothesis that alterations in the DMN are related to reduction in mind-wandering.”

Though the study was limited by a small sample size, the researchers concluded that the findings may have a host of clinical implications, including treatment of conditions linked with dysfunction of these areas, such as ADHD or Alzheimer’s disease. 11/23/2011

Primary source:

Proceedings of the National Academy of Sciences
Source reference:
Brewer JA, et al “Meditation experience is associated with diffferences in default mode network activity and connectivity” PNAS 2011.

Disclaimer The information presented in this activity is that of the authors and does not necessarily represent the views of the University of Pennsylvania School of Medicine, MedPage Today, and the commercial supporter. Specific medicines discussed in this activity may not yet be approved by the FDA for the use as indicated by the writer or reviewer. Before prescribing any medication, we advise you to review the complete prescribing information, including indications, contraindications, warnings, precautions, and adverse effects. Specific patient care decisions are the responsibilityof the healthcare professional caring for the patient.

Please review our Terms of Use. 

© 2004-2011 MedPage Today, LLC. All Rights Reserved.


The advent of MicroRNA treatments

 Here is a link to the article, which I have also copied below. This approach to combatting an illness is elegant in its conception and precise in its application, perhaps the beginning of a new era in medicine.

AASLD: MicroRNA Drug Safe in Ongoing HCV Study
By Michael Smith, North American Correspondent, MedPage Today
November 12, 2011 

MedPage Today Action Points
Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
• Explain that a novel hepatitis C virus drug (miravirsen) targeting genetic material in the liver was safe and well tolerated in a small, dose-finding clinical trial.
• Point out that in all of the doses evaluated, the drug resulted in a significant decrease in hepatitis C RNA levels, compared with placebo.
• Review

SAN FRANCISCO — A novel hepatitis C virus (HCV) drug targeting genetic material in the liver was safe and well tolerated in a small, dose-finding clinical trial, a researcher said here.

Given as monotherapy, the compound, dubbed miravirsen, induced rapid dosedependent reductions in the hepatitis C viral load, according to Harry Janssen, MD, of Erasmus Medical Center in Rotterdam, the Netherlands.

The reductions were sustained for more than a month after the end of therapy, Janssen reported at a late-breaker session during the annual meeting of the American Association for the Study of Liver Diseases. 

Miravirsen “has the potential to eradicate” hepatitis C virus either alone or as part of an interferon-free regimen, Janssen concluded.

The compound blocks a host microRNA — miR-122 — that is critical to hepatitis C accumulation in the liver, Janssen said. MicroRNAs play important roles in gene regulation and expression and Janssen said miravirsen is the first drug to exploit a microRNA target for therapy.

Indeed, of the research presented at the late-breaker session, this study is ” the most exciting because it is a whole new class of drug,” said Norah Terrault, MD, of the University of California San Francisco, who was not part of the study but who was one of the moderators of the session. 

For the study, Janssen said, researchers enrolled 36 patients with the difficult-to-treat genotype 1 of hepatitis C and assigned them to placebo or one of three doses of the drug — 3, 5, and 7 mg/kg. 

The patients, none of whom had been previously treated with pegylated interferon and ribavirin, were given five subcutaneous injections of the drug over four weeks and then followed for another 14 weeks. 

The primary endpoint was safety and tolerability, Janssen said, with viral response as a second endpoint. Not all patients have completed the study, so the researchers reported data up to week 10, six weeks after the final dose. 

Adverse events, he said, were “very much balanced” among the arms and over all “there were not a lot of side effects seen here.” Most such events were mild and none led to stopping treatment, he added. 

The only serious adverse event, in a patient receiving the high dose of the drug, was not considered related to treatment, he said. 

In all three arms, the drug resulted in a significant drop in hepatitis C RNA levels, compared with placebo. Specifically: 

The low dose (3 mg/kg) led to a 0.57 IU/mL decline in viral load, which was significant at P=0.0334.

• The medium dose (5 mg/kg) yielded a drop of 2.16 IU/mL, which was significant at P=0.007.

• The high dose (7 mg/kg) led to a decline of 2.73 IU/mL, significant at P<0.001.

Although some patients in the low- and medium-dose arms had been allowed to begin treatment with peginterferon and ribavirin three weeks after their last dose of miravirsen, those taking the high dose were not allowed standard therapy until week 10. 

Janssen said the drop in viral load seen with the high dose at week 10 “is a pure effect of miravirsen.”

The downside of the drug, Terrault told MedPage Today, is that “it has to be given by injection, and that’s always a challenging form of treatment.” 

On the other hand, it appears well tolerated and safe, with good efficacy, so “it might still be part of the mix” of treatment options. “I clearly get the sense it isn’t going to be used solo,” she said. 

The study was supported by Santaris Pharma. Janssen reported financial links with the company and one author was employed by the company. 

Terrault reported financial links with Gilead, Pfizer, Genentech, Roche, SciClone, BMS, Novartis, Eisai, and Vertex. 

Primary source: Hepatology

Source reference:

Janssen HL, et al “A randomized, double-blind, placebo (PLB) controlled safety and anti-viral proof of concept study of miravirsen (MIR), an oligonucleotide targeting miR-122, in treatment naive patients with genotype 1 (GT1) chronic HCV infection” Hepatology 2011; Abstract LB-6.

Disclaimer The information presented in this activity is that of the authors and does not necessarily represent the views of the University of Pennsylvania School of Medicine, MedPage Today, and the commercial supporter. Specific medicines discussed in this activity may not yet be approved by the FDA for the use as indicated by the writer or reviewer. Before prescribing any medication, we advise you to review the complete prescribing information, including indications, contraindications, warnings, precautions, and adverse effects. Specific patient care decisions are the responsibility of the healthcare professional caring for the patient. Please review our Terms of Use. © 2004-2011 MedPage Today, LLC. All Rights Reserved.