Recent studies show some promise in understanding chemo-caused neuropathy, and perhaps in using a common medicine to ease the worst symptoms in some people.

Study shows neuropathy relief for some using antidepressant

 A well-designed clinical study has provided the first evidence that the antidepressant Cymbalta® (duloxetine) can provide some patients with significant relief from peripheral neuropathy caused by chemotherapy.

From 20 to 40 percent of cancer patients given neurotoxic chemotherapy–taxanes, platinum-based including Eloxatin® (oxaliplatin), vinca alkaloids, bortezomib–will develop painful peripheral neuropathy (numbness, tingling, burning in hands or feet). If the pain is severe, colorectal cancer patients often have to reduce the dose or stop taking Eloxatin. Even then, this painful condition can persist for months, even years, after chemotherapy is stopped.

Previous studies have found that Cymbalta eases the neuropathy pain caused by diabetes, but this is the first comprehensive trial testing whether Cymbalta could ease neuropathy from chemotherapy. As reported in the April 3, 2013 JAMA (Journal of the American Medical Association), the trial enrolled 220 patients at 8 different cancer centers across the U.S. who still had significant neuropathy (at least 4 on a pain scale of 10) at least 3 months after chemotherapy. (Over half, 129 patients, had taken Eloxatin, mostly for colorectal cancer.) In this randomized, double-blind (neither patients nor clinicians know who’s getting the test drug), crossover trial, one-half the group received Cymbalta for 5 weeks while the others took a placebo, and then the groups switched treatments.

Of those taking Cymbalta, 59% reported at least moderately decreased pain (minimum 1 point on the 10-point scale)—usually within the first week. Among those taking a placebo first, 38% reported decreased relief. Interestingly, Cymbalta-associated pain relief was significant only in feet, not hand, symptoms. Also, 11% of people taking Cymbalta had to stop due to side effects—mostly severe fatigue.

Experts theorize that the antidepressant might help because it reduces the neurotransmitters serotonin and noradrenaline, which deliver pain messages to the brain. The study authors pointed out limitations in this first study: relatively small numbers, the effects measured by patient self-report, and the study only followed patients for 5 weeks on Cymbalta.

However, “This is not just about improving quality of life by decreasing pain, but potentially it’s helping patients live longer because they can get their full chemotherapy treatment,” noted lead author Ellen M. Lavoie Smith, Ph.D., APRN, AOCN, of the University of Michigan Comprehensive Cancer Center.

Another expert not connected to the study, Marie Bakitas, D.NSc., at the University of Alabama at Birmingham School of Nursing, noted that the trial results weren’t surprising, because duloxetine is already being used in clinics. But, she also told Medscape, other treatments such as physical therapy, acupuncture and massage “are often neglected but can be very useful.”

Sources: “Effect of Duloxetine on Pain, Function, and Quality of Life Among Patients With Chemotherapy-Induced Painful Peripheral Neuropathy,” April 3 JAMA Network; “Drug for Depression Mutes Chemo Nerve Pain,”April 2 Medscape; “Antidepressant helps relieve pain from chemotherapy, study finds,” April 2 Univ. of Michigan Health Systems press release.

Searching for genes that could predict peripheral neuropathy

 Mayo Clinic researchers have reported that they’ve found that patients with mutations in  three specific genes were more likely to suffer peripheral neuropathy from chemotherapy.

Currently, doctors have no way to predict who will have the side effect, how severe it will get, nor how long it will last.

At the recent meeting of worldwide cancer researchers (AACR, or American Association of Cancer Researchers), scientists described how they studied more than 20,000 specific genes in 119 patients—over half of whom had developed peripheral neuropathy during chemotherapy. They pinpointed three genes, in which mutations were clearly associated with developing neuropathy. Their next step will be to expand their study of the entire genome in as many as 1000 patients. The ultimate goal would be to use these types of genetic clues to potentially predict which patients might suffer side effects from specific drugs.

Fight Colorectal Cancer’s Board Chair Nancy Roach noted that these first findings are a long way from proving cause-and-effect, creating a test, and actually being able to get a reliable test to doctors and patients.

Source: “Gene Variations Predict Chemotherapy Side Effects,”April 9 2013 Science News.

Disclosure: Fight Colorectal Cancer has accepted funding from Sanofi, manufacturer of Eloxatin, in support of its programs. Fight Colorectal Cancer has ultimate authority over website content.

The U.S. Supreme Court heard arguments Monday in a case that both sides consider absolutely vital to the future of medical research.

The case: Can a company take out a patent on a human gene? Or, as the company Myriad Genetics told the Court, not actually a patent on a gene, but a patent on isolated sections of DNA molecules that they synthetically re-create in the lab to make a test for the gene.

Patents were created 150 years ago in the Constitution as temporary protection of new inventions, thus giving economic incentive for inventors. But there is a clear rule that you cannot patent “a product of nature.”

During oral arguments on Monday, justices batted back and forth discussions of making everything from baseball bats to chocolate chip cookies, as they probed lawyers’ arguments about whether the patent was for a human gene (a product of nature)—or for “a new chemical entity,” as company argued in its legal brief, created through a complicated isolation process into a synthetic section of DNA to be used as a gene test.

Thirty years ago, scientists at the Utah biotech company Myriad painstakingly unraveled the 20,000 human genes that exist in a “6-foot-long molecule that’s coiled and compacted, and stuffed into each cell”. They beat other researchers in the race to isolate two genes, known as BRCA1 and BRCA2. Mutations in those genes greatly raise the risk of breast and ovarian cancer, and that risk that can be passed on to the next generation.

Myriad holds the patent and thus sells all tests for BRAC1 and BRAC2—at least for two more years until its patent expires. Myriad and others in the biotech industry argue that invalidating gene patents would threaten billions of dollars they’ve invested in creating genetic tests, drugs, vaccines, even genetically modified crops.

Opponents from the scientific and patient advocacy community argued that no company should hold rights to what is part of a human body, because it could hinder research and in fact has hindered patient access to lifesaving information turned up in clinical trials.

The Supreme Court justices today “seemed skeptical…that human genes can be patented,” reported National Public Radio’s long-time court reporter Nina Totenberg. She cited Justice Sonia Sotomayor’s remark that it seemed ‘the isolation [of the gene] itself is not valuable,’ but rather what’s done with the isolated gene. The government’s Solicitor General Donald Verrilli agreed that a gene cannot be patented, but he noted that the cDNA—the synthetic substance derived from DNA–could be patented, leaving the gene available for general research.

That’s when they got into making cookies, and baseball bats out of trees. Justice Stephen Breyer noted, “The patient law is filled with uneasy compromises.” If you develop a new process to extract sap from a plant that can cure cancer, he said, you could patent the process, but ‘what you can’t patent is the sap itself.”

Has the horse already left the barn….or is the barn burning

Myriad’s patents at issue will expire over the next two years, and according to an April 14^thNew York Times article. ”Experts say a relatively small number of other diagnostic tests or drugs are protected by patents on single genes….It will soon be possible to sequence a person’s entire genome for less than the $4000 that Myriad charges to analyze just two genes,” and most experts believe that whole-genome sequencing might not infringe on single-gene patents.

However, two researchers reported a study in the March 25 journal Genome Medicine that there are more than 40,000 patents on DNA molecules, essentially covering the whole human genome.

Credit: XnY hateZ/Fotolia

“If these patients are enforced, our genomic liberty is lost,” lead author Dr. Christopher Mason of Weill Cornell Medical College told Science Daily on March 25^th, referring to the upcoming Supreme Court case. “Just as we enter the era of personalized medicine, we are ironically living in the most restrictive age of genomics.”The research team studied two types of DNA sequence patents—for long and short fragments. They found that 41 percent of the human genome is covered by longer DNA patents often covering whole genes. But the short-fragment patents covered DNA sequences that are found in many genes, and even outside of genes, covering virtually the whole human genome. The study examined a Myriad-patented small sequence within BRCA1, which they found in at least 689 other genes; and found the company’s patents technically cover 19 other cancers plus brain development.

Dr. Mason said he undertook the study because he knew that, in his own research into brain and cancer disorders, he was studying genes or sequences actually covered under patents. “I’m extremely pro-patent,” he said, “…but I believe individuals have an innate right to their own genome…Failure to resolve these ambiguities perpetuates a direct threat to genomic liberty.”

Who owns you, and your genes? The court case is just the opening measure in this song.

  Sources:

• “Supreme Court Asks: Can Human Genes Be Patented?”, a 7-minute NPR story explaining court case, April 15, Morning Edition  
• “Justices Appear Skeptical of Patenting Human Genes,” NPR summary of court session April 15  All Things Considered,   
• “You Don’t ‘Own’ Your Own Genes: Researchers Raise Alarm About Loss of Individual ‘Genomic Liberty’ Due to Gene Patents,” Mar. 25 2013 Science Daily,  
• “Justices Consider Whether Patents on Genes Are Valid,” April 14 New York Times  
• “Are Human Genes Patentable?” April 12 ScienceDaily

Disclosure: Fight Colorectal Cancer has accepted funding from Myriad Genetics in support of its patient education program. Fight Colorectal Cancer has ultimate authority over website content.

Time to start printing new biology textbooks: The scientific—and medical—picture of the human cell changed today from a outer-space snapshot to detailed Google map.

In a blizzard of more than 30 scientific papers published today in multiple basic scientific journals, an international research collaboration has flung open the door of the “wiring closet” of human cells–exposing at least four million gene switches that can both flick our genes on and off, and, like an electric outlet dimmer, work together in minute adjustments to turn genes up or down.

Scientists had originally assumed that only 3% of DNA was active in directing cell functions through the genes, with the other 97% of the human genome nicknamed “junk DNA” or DNA “dark matter.”

“We now know that this conclusion was wrong,” said Eric D. Green, M.D., Ph.D. , director of the National Human Genome Research Institute (NHGRI), a part of the National Institutes of Health.

 Understanding the other 97% of DNA will help scientists understand how both genetics and environmental exposures can cause diseases—from lupus to heart disease to cancer—to appear, even in one identical twin but not the other. Read the rest of this entry »

Genome sequencing lab — NIH

A Labor Day salute to the hard-working scientists—doctors, PhDs, lab techs, technology inventors—who have done some  heavy lifting to peer into the tiniest recesses of cells, genes, and molecules to unravel what makes colorectal cancer happen.

In the widest and deepest effort to date, the Cancer Genome Atlas Project has produced some surprises and key clues about colorectal cancer, published recently in the journal Nature.

It was almost “ industrial-strength genetics to try to unpick and take apart the genetic coding,” according to Dr. David Kerr, professor at the University of Oxford and Past President of the European Society for Medical Oncology. 

One of the surprises for colorectal cancer—the third cancer they’ve analyzed—is that “colon and rectal cancer are genetically virtually indistinguishable,” said Kerr. “This puts to rest a mythology …that rectal and colon cancers are somehow different beasts… There is no molecular basis for that whatsoever. They have put that mythology to bed.” Read the rest of this entry »

C3 would like to thank President Bush for signing into law the Genetic Non-Discrimination Information Act (GINA) today. This monumental legislation will protect Americans from discrimination based on an individual’s genetic information in health insurance coverage and employment settings.

“This is a tremendous victory for every American not born with perfect genes – which means it’s a victory for every single one us,” said Representative Louise Slaughter (D-NY). “Since all of us are predisposed to at least a few genetic-based disorders, we are all potential victims of genetic discrimination.”

Read the rest of this entry »