Posts Tagged ‘medicine’


A group of independent biologists say they plan to copy a costly gene therapy. Are they medicine’s Robin Hood or a threat to safety?

by Alex Pearlman

Citing the tremendous cost of new drugs, an international group of biohackers say they are creating a knock-off of a million-dollar gene therapy.

The drug being copied is Glybera, a gene therapy that was the world’s most expensive drug when it came on the market in Europe in 2015 with a $1 million per treatment price tag. Glybera was the first gene therapy ever approved to treat an inherited disease.

Now a band of independent and amateur biologists say they have engineered a prototype of a simpler, low-cost version of Glybera, and they plan to call on university and corporate scientists to help them check, improve, and test it on animals.

The group says it will start sharing the materials and describe their activities this weekend at Biohack the Planet, a conference in Las Vegas that hosts citizen scientists, journalists, and researchers for two days of presentations on body implants, biosafety, and hallucinogens.

“This was developed in a shed in Mississippi, a warehouse in Florida, a bedroom in Indiana, and on a computer in Austria,” says Gabriel Licina, a biohacker based in South Bend, Indiana. He says the prototype gene therapy cost less than $7,000 to create.

Experts briefed on the biohacking project were divided, with some calling it misguided and unlikely to work. Others say the excessive cost of genetic treatments has left patients without options and created an incentive to pirate genetic breakthroughs.

“It’s a fairly big deal to see biohackers turning their focus to gene therapies because the potential consequences can be quite large,” said Rachel Sachs, an associate professor of law at Washington University in St. Louis and an expert on drug pricing. “They may see themselves as serving the interests of the patient community.”

This year the Swiss pharmaceutical firm Novartis introduced another gene therapy, Zolgesma, for spinal muscular atrophy, with a price of $2.1 million. Because of the cost, some parents have struggled to obtain it for their children and the treatment is unlikely to be made available in most of the world.

Disrupting the narrative

The gene therapy that the biohackers say they are copying, Glybera, was approved for people with an ultra-rare blood disease called lipoprotein lipase deficiency. But it didn’t prove cost-effective and was pulled from the market in 2017 by its manufacturer, UniQure. To date, only one insurer, in Germany, is known to have paid for the treatment.

Andreas Stürmer, a biotechnologist and environmental engineer who is based in Linz, Austria, says after the idea of reverse engineering the treatment occurred to him he brought the concept to Licina. Their collaboration took place through Facebook messages and Skype calls, and included help from David Ishee, a biohacker in Mississippi.

In another recent example of copy-cat gene therapy, a biohacker in Florida in 2018 produced and ate an oral gene therapy for lactose intolerance using a 20-year-old scientific paper as a recipe.

“It’s about disrupting the narrative,” says Licina, also the cofounder of SciHouse, a community biotechnology lab in Indiana. “It was like, ‘Well, why not?”

One reason not to is that copying and selling the drug could infringe on UniQure’s intellectual property. Tom Malone, a spokesperson for UniQure, says the company had not been informed of the biohacking attempt. He says it still owns a patent on the drug but it does not believe there is strong demand for the treatment. “To that end, a “knock off” version of Glybera would likely face significant regulatory and commercial hurdles,” says Malone.

Also, the US Food and Drug Administration has said it is illegal to sell do-it-yourself gene therapy supplies. Still, some biohackers feel confident grabbing information from published papers, even if some of it has been patented. “This thing is protected 10 different ways,” says Ishee. “I don’t care. Because I’m not selling it.”

Get the job done

To make their knock-off, the biohackers checked the original Glybera papers for the information about the genetic sequence of the gene that patients require corrected copies of. They then placed an order with a gene synthesis company for a copy of the DNA, which was added to a circular genetic construct called a “minicircle.” When added to a cell, the mincircle will begin manufacturing small amounts of the lipoprotein lipase enzyme.

That is an important difference from the original Glybera, which employed an injection of viruses into the leg muscle to deliver the gene. Viral “delivery” is a complex undertaking but is the most commonly used strategy in gene therapy. The biohackers don’t have access to viruses because of their high cost, but say minicircles can potentially be injected, too.

Robert Kotin, an expert in gene therapy production, calls the minicircle technology controversial and says it has shown contradictory results. While minicircles, unlike viruses, could possibly be readministered time and again, they are not as efficient in getting cells to follow genetic instructions.

“It’s not the same [but] it can get the job done. It’s just less efficient,” says Ishee of the minicircles, which are based on his design. He thinks they could be injected over a period of half a year. “It’s like if you wanted to dig a swimming pool or a pond—you could buy a backhoe and dig it in a day or you could do it with a shovel at no cost over several months.”

https://www.technologyreview.com/s/614245/biohackers-are-pirating-a-cheap-version-of-a-million-dollar-gene-therapy/

Thanks to Kebmodee for bringing this to the It’s Interesting community.


Nourianz is the first adenosine A2A receptor antagonist approved for use in Parkinson Disease

By Brian Park

The Food and Drug Administration (FDA) has approved Nourianz (istradefylline; Kyowa Kirin) tablets as adjunctive treatment to levodopa/carbidopa in adult patients with Parkinson disease (PD) experiencing “off” episodes.

Nourianz is an oral selective adenosine A2A receptor antagonist and non-dopaminergic pharmacologic option. Adenosine A2A receptors are found in the basal ganglia of the brain where degeneration or abnormality is noted in PD; the basal ganglia are involved in motor control.

The approval was based on data from four 12-week, randomized, placebo-controlled clinical trials that evaluated the efficacy and safety of Nourianz in 1143 patients with PD taking a stable dose of levodopa/carbidopa with or without other PD medications.

Results from all 4 studies have demonstrated a statistically significant decrease from baseline in daily “off” time in patients treated with Nourianz compared with placebo. Regarding safety, the most common treatment-emergent adverse reactions were dyskinesia, dizziness, constipation, nausea, hallucination, and insomnia.

“Istradefylline is an Adenosine A2A receptor antagonist, and is a novel non-dopaminergic pharmacologic approach to treating OFF episodes for people living with PD,” said Dr Stuart Isaacson, MD, Parkinson’s Disease and Movement Disorders Center of Boca Raton, Florida. “Based on data from four clinical studies, istradefylline taken as an adjunct to levodopa significantly improved OFF time and demonstrated a well-tolerated safety profile. Istradefylline represents an important new treatment option for patients with Parkinson’s disease who experience ‘OFF’ episodes.”

The FDA had accepted the resubmitted NDA for Nourianz in April 2019 after previously rejecting the submission in 2008 due to concerns over efficacy findings.

For more information visit kyowakirin.com.

FDA Approves New Adjunct Treatment for Parkinson Disease

By Alice Park

While death is inevitable, knowing when it will come isn’t necessarily, and scientists have been trying to develop a test that could reliably and easily predict how long a person will live — or, more technically, how healthy they are and therefore how vulnerable they might be to major mortality risk factors. Blood tests are the most likely avenue to such a test, since it’s easy to obtain blood samples and labs equipped to handle them are common.

The latest effort is described in a new paper published in Nature Communications, by a team led by Joris Deelen, postdoctoral researcher at the Max Planck Institute for the Biology of Aging and P. Eline Slagboom, head of molecular epidemiology at Leiden University Medical Center. The researchers report that, in a group of more than 44,000 healthy patients, their blood test was around 80% accurate in predicting mortality risk within five to 10 years.

The patients, who ranged in age from 18 to 109 years, provided blood samples and had their health events tracked for up to 16 years. The researchers analyzed a group of 226 so-called metabolites, or by-products of things that various cells and tissues in the body pour into the blood stream for circulation and removal. From this collection of markers, the team narrowed down the list to 14 that they determined could together, and along with the person’s sex, provide a pretty good picture of each person’s health risk, and, by association, their risk of dying in the next five to 10 years. They accomplished this by comparing those who died during the study to those who did not and isolating which agents in their blood differed to statistically significant amounts. The link between the final 14 factors and mortality remained strong even after the scientists accounted for potential confounding factors that also affect survival such as age, sex, and cause of death.

“We want to tackle the vulnerability of people’s health that is hidden and that doctors cannot see from the outside,” says Slagboom. “I am still surprised by the fact that in a group of people you can take one blood sample at one point of time in their life, and that would say anything meaningful about their five to 10 year mortality risk.”

Both Deelen and Slagboom stress that the test is not ready yet for doctors to use in the clinic with their patients, but that it does establish a foundation for one down the road. An eventual test could be most useful at first in assessing older patients and guiding treatment decisions, since the 14 metabolites represent a range of processes including the breakdown of fat and glucose, inflammation and fluid balance in the body, that impact a range of chronic ailments, as well as a person’s ability to recover from illness or injury.

Researchers at Leiden University are currently studying the test to see if it can help doctors predict which patients with hip fractures are more likely to develop complications during their recovery after surgery. Another study is looking at whether the test can predict which people with kidney failure are more likely to develop dementia or side effects like delirium as a result of their treatment; this information could help doctors to better adjust dosage and treatment decisions.

The researchers are also hoping to work with large databanks around the world to further validate the findings. “We see this as a foundation,” says Slagboom, “we do not see this test as an endpoint.”

https://time.com/5656767/blood-test-longevity/


Brain tissue from deceased patients with Alzheimer’s has more tau protein buildup (brown spots) and fewer neurons (red spots) as compared to healthy brain tissue.

By Yasemin Saplakoglu

Alzheimer’s disease might be attacking the brain cells responsible for keeping people awake, resulting in daytime napping, according to a new study.

Excessive daytime napping might thus be considered an early symptom of Alzheimer’s disease, according to a statement from the University of California, San Francisco (UCSF).

Some previous studies suggested that such sleepiness in patients with Alzheimer’s results directly from poor nighttime sleep due to the disease, while others have suggested that sleep problems might cause the disease to progress. The new study suggests a more direct biological pathway between Alzheimer’s disease and daytime sleepiness.

In the current study, researchers studied the brains of 13 people who’d had Alzheimer’s and died, as well as the brains from seven people who had not had the disease. The researchers specifically examined three parts of the brain that are involved in keeping us awake: the locus coeruleus, the lateral hypothalamic area and the tuberomammillary nucleus. These three parts of the brain work together in a network to keep us awake during the day.

The researchers compared the number of neurons, or brain cells, in these regions in the healthy and diseased brains. They also measured the level of a telltale sign of Alzheimer’s: tau proteins. These proteins build up in the brains of patients with Alzheimer’s and are thought to slowly destroy brain cells and the connections between them.

The brains from patients who had Alzheimer’s in this study had significant levels of tau tangles in these three brain regions, compared to the brains from people without the disease. What’s more, in these three brain regions, people with Alzheimer’s had lost up to 75% of their neurons.

“It’s remarkable because it’s not just a single brain nucleus that’s degenerating, but the whole wakefulness-promoting network,” lead author Jun Oh, a research associate at UCSF, said in the statement. “This means that the brain has no way to compensate, because all of these functionally related cell types are being destroyed at the same time.”

The researchers also compared the brains from people with Alzheimer’s with tissue samples from seven people who had two other forms of dementia caused by the accumulation of tau: progressive supranuclear palsy and corticobasal disease. Results showed that despite the buildup of tau, these brains did not show damage to the neurons that promote wakefulness.

“It seems that the wakefulness-promoting network is particularly vulnerable in Alzheimer’s disease,” Oh said in the statement. “Understanding why this is the case is something we need to follow up in future research.”

Though amyloid proteins, and the plaques that they form, have been the major target in several clinical trials of potential Alzheimer’s treatments, increasing evidence suggests that tau proteins play a more direct role in promoting symptoms of the disease, according to the statement.

The new findings suggest that “we need to be much more focused on understanding the early stages of tau accumulation in these brain areas in our ongoing search for Alzheimer’s treatments,” senior author Dr. Lea Grinberg, an associate professor of neurology and pathology at the UCSF Memory and Aging Center, said in the statement.

The findings were published Monday (Aug. 12) in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.

https://www.livescience.com/alzheimers-attacks-wakefulness-neurons.html?utm_source=notification

A 7-year-old boy complaining of jaw pain was found to have 526 teeth inside his mouth, according to the hospital in India where he was treated.

The boy was admitted last month in the southern city of Chennai because of swelling and pain near his molars in his lower right jaw.

When doctors scanned and x-rayed his mouth, they found a sac embedded in his lower jaw filled with “abnormal teeth,” Dr. Prathiba Ramani, the head of Oral and Maxillofacial Pathology at Saveetha Dental College and Hospital, told CNN.

While the surgery to remove the teeth took place last month, doctors needed time to individually examine each tooth before they could confirm their findings.

After discovering the sac, two surgeons removed it from the boy’s mouth. Then Ramani’s team took four to five hours to empty the sac to confirm its contents and discovered the hundreds of teeth.

“There were a total of 526 teeth ranging from 0.1 millimeters (.004 inches) to 15 millimeters (0.6 inches). Even the smallest piece had a crown, root and enamel coat indicating it was a tooth,” she said.

The boy was released three days after the surgery and is expected to make a full recovery, Ramani said.

Ramani said the boy was suffering from a very rare condition called compound composite odontoma. She said what caused the condition is unclear, but it could be genetic or it could be due to environmental factors like radiation.

The boy actually may have had the extra teeth for some time. His parents told doctors that they had noticed swelling in his jaw when he was as young as 3, but they couldn’t do much about it because he would not stay still or allow doctors to examine him.

Dr. P. Senthilnathan, head of the hospital’s Oral and Maxillofacial Surgery Department and one of two surgeons who operated on the boy, detailed the procedure to CNN.

“Under general anesthesia, we drilled into the jaw from the top,” he said. “We did not break the bone from the sides, meaning reconstruction surgery was not required. The sac was removed. You can think of it as a kind of balloon with small pieces inside.”

Dr. Senthilnathan said the discovery showed it was important to seek treatment for dental issues as early as possible.

Awareness about dental and oral health was improving, he said, though access in rural areas remained problematic.

“Earlier, things like not as many dentists, lack of education, poverty meant that there was not as much awareness. These problems are still there.

“You can see people in cities have better awareness but people who are in rural areas are not as educated or able to afford good dental health.”

In Ravindrath’s case, all has turned out well; the boy now has a healthy count of 21 teeth, Dr. Senthilnathan said.

Doctors find 526 teeth in boy’s mouth after he complains of jaw pain

by Ed Cara

People who only occasionally fall down an internet rabbit hole on their smartphones late at night might be able to rest easier—at least according to the results of a new study in mice. Researchers found that short bursts of light exposure at night won’t necessarily disrupt your internal clock, including sleep habits.

The researchers used mice to study the circadian rhythm. In both mice and humans, the circadian rhythm is primarily controlled by the brain’s suprachiasmatic nucleus (SCN), a tiny region found in the hypothalamus. One crucial aspect of the SCN involves regulating our sleep/wake, or light/dark, cycle. It’s long been thought that any kind of light exposure our eyes take in affects the SCN, and thus, can affect our sleep.

“Light information comes into the SCN, and that’s what synchronizes all of the body’s clocks to the light/dark cycle,” said lead author Tiffany Schmidt, a neurogeneticist at Northwestern, in a release from the university. “This one master pacemaker makes sure everything is in sync.”

Schmidt and her team wanted to test this long-held theory that the SCN responds to any light exposure. So they bred mice that had light-sensitive nerve cells in the retina that were only capable of communicating with the SCN. Then they exposed these mice to light for short periods of time.

Because mice, unlike people, are nocturnal, the light should have made them want to fall asleep. But they instead just carried out on with their day, sleeping and waking as normal. Their body temperature, which fluctuates predictably before, during, and after sleep, also followed the same pattern seen in mice with normal circadian rhythms.

What this could mean, according to the authors, is that our brains respond to acute light—meaning brief exposures to light—through a different neural pathway than what’s used for long periods of light exposure, a pathway that doesn’t involve the SCN.

“If these two effects—acute and long-term light exposure—were driven through the same pathway, then every minor light exposure would run the risk of completely shifting our body’s circadian rhythms,” Schmidt said.

The findings will be published this week in the journal eLife.

Mice and their brains aren’t a perfect proxy for people, obviously. And even if the same general principle does apply to us, Schmidt and her team say there’s no clear lead on where these other pathways could exist in the brain. And there’s undoubtedly a point where being exposed to light late at night too long or too often can start to affect our internal clock—even if where that point lies is still a mystery right now. There needs to be a lot much research studying these questions and others.

What is clear, the authors cautioned, is that chronic nighttime light exposure, and the disruptions to our sleep it can cause, can be very bad for health. In other words, don’t use this study as an excuse to start regularly binge-watching Netflix till 4 a.m.

“Light at the wrong time of day is now recognized as a carcinogen,” Schmidt said. “We want people to feel alert while they are exposed to light without getting the health risks that are associated with shifted circadian rhythms, such as diabetes, depression and even cancer.”

https://gizmodo.com/checking-your-phone-at-night-wont-necessarily-throw-off-1836603924

Users of prosthetic limbs could soon be able to feel sensation on them, thanks to an “electronic skin” (e-skin) invented by researchers from the National University of Singapore (NUS).

The artificial nervous system can detect touch more than 1,000 times faster than the human equivalent and is the first e-skin in the world to do so, according to Assistant Professor Benjamin Tee from the Department of Materials Science and Engineering at the NUS Faculty of Engineering, who led the research.

Previously, damaged e-skins would lose their function due to their interlinked wiring system.

But if a corner of the Asynchronous Coded Electronic Skin (Aces) nervous system tears, the rest of the skin continues to have sensation, just like human skin, the researchers said.

This is because the Aces detects signals like the human nervous system and it comprises a network of sensors – each working independently – connected via a single electrical conductor.

The research team, which took 11/2 years to develop the sensor system, published its innovation in Science Robotics journal today.

“When you lose a limb and get fitted with a prosthetic that doesn’t feel, it’s almost like you’re always feeling numb and cannot control things very well,” said Prof Tee. “If we have a skin that can make prosthetics smarter, we can restore motor functions, productivity and general quality of life for these people.”

In human skin, receptors send information about touch to the brain, which enables humans to intuitively sense touch.

When the Aces is attached to a prosthetic hand, a neural implant must be inserted into the patient’s arm so that the brain can detect the sense of touch from the e-skin.

The team will work with prosthetics researchers abroad to conduct a clinical trial of the e-skin with a patient using an artificial hand.

The Aces has also been designed for robots. “Robots need to have a sense of touch to interact better with humans, but robots today still cannot feel objects very well,” said Prof Tee.

For instance, a search-and-rescue robot digging through rubble will need sensation to know that it has to push away rocks and concrete to rescue a trapped person.

E-skin such as the Aces can be commercialised for robots within a year or two, Prof Tee said, but it will take five to 10 years for prosthetics that sense touch to reach patients, to allow for clinical trials.

https://www.straitstimes.com/singapore/prosthetics-can-sense-touch-with-electronic-skin-invention