‘Cannibal disease’ study revels gene that produces CJD resistance

Researchers studying a neurological disease associated with cannibalism have discovered a natural genetic variation that produces resistance to brain diseases such as Creutzfeldt-Jakob disease and bovine spongiform encephalopathy, also known as “mad cow disease.”

Their discovery could be the first step toward understanding how neurodegenerative disorders such as Creutzfeldt-Jakob disease (CJD) and others dementias could be prevented and treated.

The study, published in Nature, was conducted by researchers from the UK Medical Research Council’s (MRC) Prion Unit at University College London (UCL) in the UK.

Prions are infectious proteins that can cause lethal neurodegenerative diseases. In addition to causing diseases such as CJD and mad cow disease (BSE), prions are also a rare cause of dementia.

These proteins damage the brain by changing shape and forming misshapen chains. This process has also been identified in Parkinson’s disease and common forms of dementia such as Alzheimer’s disease.

One disease caused by prions that has been studied at the MRC’s Prion Unit is kuru, a rare disease that was typically found in a remote region of Papua New Guinea, among a community that consumed the brains of their dead as part of a funeral ritual.

In the late 1950s, at the height of a kuru epidemic, up to 2% of the population was killed by the disease each year. The mortuary feasts of the Fore people stopped in 1960, yet cases of the disease were reported in subsequent years, indicating that kuru has a long incubation period. It is now believed that the average incubation period for kuru is 10-13 years.

Experts believe that those who survived exposure to kuru may have a genetic resistance to the disease, and that the identification of any genetic changes that may have occurred could provide insight into how similar diseases such as CJD could be prevented or treated.

‘A striking example of Darwinian evolution in humans’

Working alongside colleagues at the Papua New Guinea Institute, the researchers discovered a specific gene – the prion protein gene – carried by some of the survivors of kuru that they believed might confer protection from the disease.

To investigate, the team bred mice with the same genetic change as that found in the kuru survivors. They achieved this by altering one of the amino acids that the prion protein is comprised of. The researchers then exposed the mice to kuru and CJD to test for resistance.

The team discovered that the mice were completely resistant not only to kuru but all forms of CJD too, including a form caused by human infection with BSE.

“From the human genetic work the Unit has carried out in Papua New Guinea we were expecting the mice to show some resistance to disease,” says study leader Dr. Emmanuel Asante. “However, we were surprised that the mice were completely protected from all human prion strains. The result could not have been clearer or more dramatic.”

The researchers believe that if they can work out how this change to the prion protein structure prevents it from changing shape and forming damaging chains, they may be able to discover a way to prevent CJD and other dementias caused by these chains of misshapen proteins.

“This is a striking example of Darwinian evolution in humans – the epidemic of prion disease selecting a single genetic change that provided complete protection against an invariably fatal dementia,” states Prof. John Collinge, leader of the kuru research program.

“Much work is now ongoing in the MRC Unit to understand the molecular basis of this effect which we expect to provide key insights into how seeds of other misshapen proteins develop in the brain and cause the common forms of dementia, thereby guiding us to new treatments in the years ahead.”

Last year, Medical News Today reported on a study suggesting that there could be a way to harness the brain’s capacity to self-repair and preserve brain function in brain-wasting prion diseases.

Written by James McIntosh

Copyright: Medical News Today


Veterans say VA Policy on Marijuana and Painkillers Lacking Consistency

Austin American-Statesman | Jun 15, 2015 | by Jeremy Schwartz

Since early 2013, Vietnam veteran Bill Williams had received daily doses of hydrocodone to help him deal with chronic leg and back pain. For more than 30 years, he has taken anti-anxiety drugs like Valium to help with the post-traumatic stress disorder he developed after a lengthy tour on a Navy submarine.

Occasionally, the 62-year-old Brackettville resident would smoke marijuana, which he said provided relief for his pain and PTSD in ways the pharmaceuticals could not. His experience with that drug, which he said also helped him sleep, mirrors that of a growing number of veterans who have turned to medical marijuana as an alternative to traditional treatments.

At first, he said, his Department of Veterans Affairs doctors tolerated his marijuana use, telling him that if it helped his symptoms he should continue. But that changed with the introduction of stricter VA policies on narcotic painkillers, the result of new Drug Enforcement Administration rules on hydrocodone and a VA push to reduce the number of patients receiving the medications.

In April, after he tested positive for marijuana, the VA canceled his hydrocodone prescription.

The incident is emblematic of a brewing battle over marijuana use among veterans suffering with chronic pain and anxiety disorders and the VA’s evolving, sometimes confusing, position as more states legalize the drug.

“There is no consistency, even in the states where it’s legal,” said Roger Martin, executive director of Grow4Vets, which advocates for marijuana treatment of pain and PTSD.

As a federal agency, the VA is in an unusual position. It recognizes marijuana possession as a federal offense, but its policy doesn’t prohibit veterans who get state-sanctioned medical marijuana from participating in VA pain control programs.

And officials say a positive marijuana test doesn’t automatically result in an opioid prescription cancellation, but should cause doctors to assess patients for “misuse, adverse effects and withdrawal.” The decision to halt opioid drugs when a patient uses marijuana “need(s) to be made by individual providers in partnership with their patients,” the agency’s policy states.

But in states such as Texas, where marijuana isn’t legal, the VA’s policy is less clear. Asked specifically about marijuana use by Texas patients, VA officials couldn’t provide clarification.

Williams’ doctor at the San Antonio VA, for example, told him that the agency’s policies provided no wiggle room. “Due to the presence of the marijuana, based on current VA practice guidelines, I am unable to prescribe further controlled substances (hydrocodone) at this time,” he wrote in a letter to Williams.

Martin said his group has heard from a number of veterans like Williams who say their painkiller prescriptions have been abruptly canceled in recent months because of marijuana use.

“It’s a flat-out violation of the Hippocratic oath,” he said. “It puts veterans and the people around them in danger.”

Pain specialist Dr. C.M. Schade, director emeritus of the Texas Pain Society, said that civilian doctors in Texas must halt narcotic prescriptions for patients who test positive for controlled substances; they can be resumed once the patient stops taking the illegal drug or enters treatment.

Williams said he stopped smoking marijuana months before his positive test, which he blamed on secondhand smoke from toking friends, but he acknowledged previous positive tests. But he said that shouldn’t disqualify him from receiving the pain medication he needs to function on a daily basis, especially if it is allowed in states like Colorado and Washington.

He recently underwent a procedure to burn the nerve endings in his back, which should give him relief for several months, but he fears for the future.

“What’s scaring me is that in (the coming) months, when I’m going to need pain medication, are they going to give it to me?” he said. “I’m not a person that’s going to go beg the VA for pain meds. I have a high tolerance for pain. But once those nerves grow back I won’t be able to live with it.”

Related Topics
Department of Veteran Affairs, PTSD

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Fusion Cells Leading to Cancer?

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Copyright: Medical News Today

As the number two leading cause of death in the US, cancer touches just about everyone in some way. There are many factors involved in the formation of cancer, and genetic changes are a key culprit. Now, a new study sheds light on how the fusion of one normal cell with another can trigger genomic events that turn normal cells cancerous, allowing tumors to form.

According to the American Cancer Society, in the US in 2015, around 1.6 million new cancer cases will be diagnosed, and over 589,000 individuals will die from the disease.

To further investigate causes for this ubiquitous condition, researchers from the University of Michigan and the Mayo Clinic undertook a study that is published in The American Journal of Pathology.

They note that exposure to carcinogens and infectious agents can trigger spontaneous genetic mutations that arise when cells divide. Some researchers, however, believe that the link between carcinogens and genetic changes are too uncertain to account fully for the development of common cancers.

However, researchers have suspected that cell fusion – the process whereby one or more cells combine to form a new cell with multiple nuclei – is a potential cause for some cancers, providing a reason why multiple genetic changes appear to underpin cancer development.

But there has been a lack of clear evidence that normal cell fusion alone could trigger cancer – until now, that is. In their latest study, the researchers show the missing link between cell fusion and the multiple genetic changes that transform normal cells into cancerous cells.

Additionally, the team has been able to show how, when injected into live animals, these fused cells form tumors.

‘Cell fusion generates chromosomal instability’

To conduct their study, the researchers used rat IEC-6 intestinal epithelial cells. They explain that these cells maintain a “stable diploid genomic structure” (one with two sets of chromosomes), replicate normally and lack the cellular features of cancer cells. These cells also do not form tumors when observed over several generations.

The team labeled the IEC-6 cells with either red or green dyes and then exposed them to 50% polyethylene glycol to facilitate cell fusion. The researchers could then determine if the cells had fused by noting the presence of both the red and green dyes within one cell.

While non-fused cells only contained one color, the researchers also noted that fused cells were larger than their non-fused counterparts.

Results reveal that fused cells can replicate – 19% of fused IEC-6 cells generated clones – and with replication, the chromosomes from the two separate cells fused together.

Additionally, the researchers found that 41% of the clones had abnormal numbers of chromosomes, 56% were near-diploid and 4% were tetraploid. In contrast, 86% of the non-fused cells were diploid.

Dr. Jeffrey L. Platt, from the University of Michigan-Ann Arbor, says their results “indicate that cell fusion generates chromosomal instability,” which refers to changes in the appearance and number of chromosomes. Because such abnormalities are typically observed in cancer, the team looked for DNA damage in the fused clones and found such damage in significantly more fused clones than non-fused clones.

They say their findings suggest that after cells fuse, a chromosomal instability might result in DNA damage and, therefore, genetic changes that underpin cancer.

Commenting on their findings, cancer specialist William B. Coleman, PhD, from the University of North Carolina Comprehensive Cancer Center in Chapel Hill, says:

“The frequency of cell fusion events in vivo is not known, although cell fusion is thought to occur under some circumstances such as cell injury, inflammation and viral infection. Although fusion of normal cells in vitro and in vivo may be a rare event, this study shows that cell fusion between normal cells can have pathological consequences.”

He adds that their results “provide evidence for another molecular mechanism driving neoplastic transformation – genomic catastrophe.”

Fused cells form tumors in mice

Interestingly, the team also found that when they transplanted IEC-6 cells into immunodeficient mice, during 12 weeks, they generated tumors in 61% of the hosts. In contrast, no tumors formed from the cells that did not fuse.

“We believe one cell fusion event can both initiate malignancy and fuel evolution of the tumor that ensues,” says lead author Xiaofeng Zhou, from the University of Michigan-Ann Arbor.

Dr. Coleman also adds that most cases of human spontaneous cancer are believed to come from cells that underwent random DNA damage or random errors during replication.

He calls for further research to determine whether cell fusion events between normal human cell types can bring about genomic catastrophe and neoplastic transformation.

Last week, Medical News Today reported on two studies that suggested immunotherapy is highly effective against cancer.