Is it time to rethink the potential of a much-maligned female organ?
She’s the third person ever to be cured. Researchers announced that the new approach holds the potential for curing more people of racially diverse backgrounds.
Most muscles in our bodies only act in response to incoming nerve signals, which have to trigger each individual muscle cell to contract or relax. But heart muscle is different. The impulses that trigger contraction in heart muscle are passed from one muscle cell to its neighbors, leading to a rhythmic wave of contractions. This is so thoroughly built into the system that a sheet of heart muscle cells in a culture dish will start contracting spontaneously.
Now, researchers have taken advantage of some of the unique properties of cardiac cells to build a swimming robot fish powered by nothing but sugar. And while they tried to craft the heart’s equivalent of a pacemaker, it turned out not to be needed: the right arrangement of muscle cells got the fish swimming spontaneously.
Building a heart-like muscle
In some ways, the paper describing the new robot fish is a tribute to our growing ability to control stem cell development. The researchers behind the paper, based at Harvard, decided to use cardiac muscle cells to power their robot. A couple of years ago, this would have meant dissecting out a heart from an experimental animal before isolating and growing its cardiac cells in culture.
By tracking every cell in an organism, scientists are working out why certain cancer treatments fail, which could lead to improved medicine.
In 1961, Osamu Shimomura and Frank Johnson isolated a protein from jellyfish that glow green under UV light. Corals, too, can fluoresce in a wide range of hues, thanks to similar proteins. Now, scientists at Harvard University have genetically modified the three-banded panther worm to enable the creature to emit a similar green glow, according to a new paper published in the journal Developmental Cell. Their hope is to uncover the secrets to regeneration.
Most animals exhibit some form of regeneration: regrowing hair, for instance, or knitting a fractured bone back together by growing new skin. But some creatures are capable of particularly amazing regenerative feats, and studying the mechanisms by which they accomplish this could have important implications for human aging. If a salamander loses a leg, the limb will grow back, for example, while some geckos can detach their tails as a distraction to evade predators and then regrow them later. The zebrafish can regrow a lost or damaged fin, as well as repair a damaged heart, retina, pancreas, brain, or spinal cord. Cut a planarian flatworm, a jellyfish, or a sea anemone in half, and it will regenerate its entire body.
And then there is the three-banded panther worm (Hofstenia miamia), a tiny creature that looks a bit like a plump grain of rice, so named because of its trademark trio of cream-colored stripes across its body. If a panther worm is cut into three parts, each part will generate into a fully formed worm within eight weeks or so. These worms are found primarily in the Caribbean, Bahamas, and Bermuda, as well as Japan, and they are voracious predators, not above taking a few bites out of their fellow panther worms if they’re hungry enough and can’t find other prey. And they offer a promising new model for studying the mechanics of regeneration.
By observing mice hair follicles, scientists discovered an unexpected mechanism of aging. “If I didn’t see it with my own eyes I wouldn’t believe it,” one said.
In the US, September is National Prostate Cancer Awareness Month. This feature highlights why catching prostate cancer early can be critical, and what researchers are doing to improve the odds of controlling the disease once it’s found.
Prostate cancer is a paradox. It has one of the highest early-stage survival rates of any cancer, yet it’s the second most common cause of cancer death in the US among people with a prostate (behind only lung cancer). Localized prostate cancer, only found in the organ itself, is highly curable. But once it becomes metastatic, spreading beyond the prostate, it is incurable and leads to death.
This makes studying it complicated. How do you understand something that is at once easy and impossible to cure? Researchers tackling the paradox are harnessing technologies like imaging, genetic sequencing, big data, and artificial intelligence to work toward changing outcomes for patients across the spectrum of cancer severity. From understanding what makes the cancer develop in the first place to identifying new drugs and new methods of treatment—each innovation is an opportunity to save lives. Here’s a look at just a few of the countless projects in progress around the world that could one day change the treatment landscape for prostate cancer.
New research is intensifying the debate — with profound implications for the future of the planet.
What are the key differences between modern humans and our closest relatives, the Neanderthals and Denisovans? For the Neanderthals, there doesn’t look to be any sort of obvious difference. They used sophisticated tools, made art, and established themselves in some very harsh environments. But, as far as we can tell, their overall population was never particularly high. When modern humans arrived on the scene in Eurasia, our numbers grew larger, we spread even further, and the Neanderthals and Denisovans ended up displaced and eventually extinct.
With our ability to obtain ancient DNA, we’ve now gotten a look at the genomes of both Neanderthals and Denisovans, which allows us to ask a more specific question: could some of our differences be due to genetics?
The three species are close relatives, so the number of differences in our proteins are relatively small. But a large, international research team has identified one and engineered it back into stem cells obtained from modern humans. And the researchers found that neural tissue made of these cells has notable differences from the same tissue grown with the modern human version of this gene.
Tricia Derges, a Republican state representative in Missouri, falsely claimed to patients at her medical clinic that she was injecting them with stem cells, prosecutors said.
Our visual system is complex, with photoreceptors that pick up incoming light and at least three types of neurons between those and the brain. Once in the brain, visual input is interpreted by multiple dedicated regions that build a scene out of small pieces of shape and motion. The outcome of that processing may be further interpreted by areas of the brain that handle things like reading or face recognition.
With all that complexity, lots of different things can go wrong. Accordingly, we’ll likely need multiple solutions if we want to try to correct these problems. So, it was nice to see the results of two very different approaches to tackling visual problems tested in experimental animals this week. One group manipulated biology to correct problems in the transmission of information between the eye and the brain, while another group used electronics to bypass the need for an eye entirely.
One of the most exciting developments in tissue repair has been the recognition that we could convert many cell types into stem cells just by activating four specific genes. Unfortunately, activating those genes widely in mice kills them, as the genes also promote loss of normal cellular identity and uncontrolled division. A huge, US-based collaboration suspected many of these problems were due to one of those four genes (called MYC), and so it focused on working with the remaining three. The first showed that activating these three in cells from older mice restored properties that were typical of younger cells without any loss of normal cell function.
The bones are among the hardest to replace in the body. A trial of the new technique in humans is about to begin.
Known initially as the “Berlin Patient,” he underwent an experimental stem cell transplant 13 years ago that rid his body of the virus. He died of leukemia.
Researchers discovered a way to awaken dormant stem cells and transform them into cartilage. If the technique works in humans, it may help ease debilitating joint pain.
California-based startup Mission Bio has raised a new $70 million Series C funding round, led by Novo Growth and including participating from Soleus Capital and existing investors Mayfield, Cota and Agilent. Mission Bio will use the funding to scale its Tapestri Platform, which uses the company’s work in single-cell multi-omics technology to help optimize clinical trials for targeted, precision cancer therapies.
Mission Bio’s single-cell multi-omics platform is unique in the therapeutic industry. What it allows is the ability to zero in on a single cell, observing both genotype (fully genetic) and phenotype (observable traits influenced by genetics and other factors) impact resulting from use of various therapies during clinical trials. Mission’s Tapestri can detect both DNA and protein changes within the same single cell, which is key in determining effectiveness of targeted therapies because it can help rule out the effect of other factors not under control when analyzing in bulk (ie. across groups of cells).
Founded in 2012 as a spin-out of research work conducted at UCSF, Mission Bio has raised a total of $120 million to date. The company’s tech has been used by a number of large pharmaceutical and therapeutic companies, including Agios, LabCorp and Onconova Therapeutics, as well as at cancer research centers including UCSF, Stanford and the Memorial Sloan Kettering Cancer Center.
In addition to helping with the optimization of clinical trials for treatments of blood cancers and tutors, Mission’s tech can be used to validate genome editing – a large potential market that could see a lot of growth over the next few years with the rise of CRISPR-based therapeutic applications.
Stem cells hold the promise of helping us repair tissues damaged by disease or injury. But outside of bone marrow stem cells, the practice remains largely a promise, as we’re just starting clinical trials to determine if we can use these cells effectively. But that hasn’t stopped people from offering stem cell “treatments” with no basis in evidence. Many of the clinics that offer these services are based overseas, leading to what’s been termed “stem cell tourism.” But a number take advantage of ambiguities in Food and Drug Agency regulations to operate in the United States.
A new survey of doctors suggests that a surprising number of their patients are using these services—sometimes with severe consequences. And many doctors don’t feel like they’re prepared to deal with the fallout.
The work focuses on neurologists, who specialize in treating diseases of the nervous system. These include diseases like Parkinson’s and multiple sclerosis, for which there are few effective treatments—although stem cells have undergone some preliminary tests in the case of Parkinson’s. Given the lack of established options, it wouldn’t be surprising if these patients turned to therapies that haven’t been established, like those involving stem cells.
Bit Bio, the new startup which pitches itself as the “enter button for the keyboard to the software of life” only needed three weeks to raise its latest $41.5 million round of funding.
Originally known as Elpis Biotechnology and named for the Greek goddess of hope, the Cambridge, England-based company was founded by Mark Kotter in 2016 to commercialize technology that can reduce the cost and increase the production capacity for human cell lines. These cells can be used in targeted gene therapies and as a method to accelerate drug discovery at pharmaceutical companies.
The company’s goal is to be able to reproduce every human cell type.
“We’re just at a very crucial time in biology and medicine and the bottleneck that has become really clear is a scalable source of robust human cells,” said Kotter. “For drug discovery this is important. When you look at failure rates in clinical trials they’re at an all time high… that’s in direct contradiction to the massive advancements in biotechnology in research and the field.”
In the seventeen years since scientists completely mapped the human genome, and eight years since scientists began using the gene editing technology known as CRISPR to edit genetic material, there’s been an explosion of treatments based on individual patient’s genetic material and new drugs developed to more precisely target the mechanisms that pathogens use to spread through organisms.
These treatments and the small molecule drugs being created to stop the spread of pathogens or reduce the effects of disease require significant testing before coming to market — and Bit Bio’s founder thinks his company can both reduce the time to market and offer new treatments for patients.
It’s a thesis that had investors like the famous serial biotech entrepreneur, Richard Klausner, who served as the former director of the National Cancer Institute and founder of revolutionary biotech companies like Lyell Immunopharma, Juno, and Grail, leaping at the chance to invest in Bit Bio’s business, according to Kotter.
Joining Klausner are the famous biotech investment firms Foresite Capital, Blueyard Capital and Arch Venture Partners.
“Bit Bio is based on beautiful science. The company’s technology has the potential to bring the long-awaited precision and reliability of engineering to the application of stem cells,” said Klausner in a statement. “Bit Bio’s approach represents a paradigm shift in biology that will enable a new generation of cell therapies, improving the lives of millions.”
Kotter’s own path to develop the technology which lies at the heart of Bit Bio’s business began a decade ago in a laboratory in Cambridge University. It was there that he began research building on the revolutionary discoveries of Shinya Yamanaka, which enabled scientists to transform human adult cells into embryonic stem cells.
“What we did is what Yamanaka did. We turned everything upside down. We want to know how each cell is defined… and once we know that we can flip the switch,” said Kotter. “We find out which transcription factors code for a single cell and we turn it on.”
Kotter said the technology is like uploading a new program into the embryonic stem cell.
Although the company is still in its early days, it has managed to attract a few key customers and launch a sister company based on the technology. That company, Meatable, is using the same process to make lab-grown pork.
Meatable is the earliest claimant to a commercially viable, patented process for manufacturing meat cells without the need to kill an animal as a prerequisite for cell differentiation and growth.
Other companies have relied on fetal bovine serum or Chinese hamster ovaries to stimulate cell division and production, but Meatable says it has developed a process where it can sample tissue from an animal, revert that tissue to a pluripotent stem cell, then culture that cell sample into muscle and fat to produce the pork products that palates around the world crave.
“We know which DNA sequence is responsible for moving an early-stage cell to a muscle cell,” says Meatable chief executive Krijn De Nood.
If that sounds similar to Bit Bio, that’s because it’s the same tech — just used to make animal instead of human cells.
If Meatable is one way to commercialize the cell differentiation technology, Bit Bio’s partnership with the drug development company Charles River Laboratories is another.
“We actually do have a revenue generating business side using human cells for research and drug discovery. We have a partnership with Charles River Laboratories the large preclinical contract research organization,” Kotter said. “That partnership is where we have given early access to our technology to Charles River… They have their own usual business clients who want them to help with their drug discovery. The big bottleneck at the moment is access to human cells.”
Drug trials fail because the treatments developed either are toxic or don’t work in humans. The difference is that most experiments to prove how effective the treatments are rely on animal testing before making the leap to human trials, Kotter said.
The company is also preparing to develop its own cell therapies, according to Kotter. There, the biggest selling point is the increased precision that Bit Bio can bring to precision medicine, said Kotter. “If you look at these cell therapies at the moment you get mixed bags of cells. There are some that work and some that have dangerous side effects. We think we can be precise [and] safety is the biggest thing at this point.”
The company claims that it can produce cell lines in less than a week with 100 percent purity, versus the mixed bags from other companies cell cultures.
“Our moonshot goal is to develop a platform capable of producing every human cell type. This is possible once we understand the genes governing human cell behaviour, which ultimately form the ‘operating system of life’,” Kotter said in a statement. “This will unlock a new generation of cell and tissue therapies for tackling cancer, neurodegenerative disorders and autoimmune diseases and accelerate the development of effective drugs for a range of conditions. The support of leading deep tech and biotech investors will catalyse this unique convergence of biology and engineering.”
Since 2012, Dr. Jeanne Loring, the founder of the eponymous Loring Lab at Scripps Research, has been thinking about how to use pluripotent stem cells as a potential treatment for Parkinson Disease.
Now, eight years later, Aspen Neuroscience, the company she founded to bring her research to market has raised $70 million in funding and is set to begin clinical trials.
Roughly 60,000 Americans are diagnosed with Parkinson disease, which destroys parts of the brain responsible for motor function. The disease causes a debilitating loss of movement as a result of the degradation of a specific type of neuron in the brain responsible for the production of dopamine — a chemical that facilitates the brain’s control of mood and movement.
Aspen’s experimental treatment takes skin cells from patients who already have Parkinson’s disease and converts those cells into pluripotent stem cells using the technique that won Shinya Yamanaka and John Gurdon the Nobel Prize for medicine back in 2012.
It was Yamanaka’s discovery that in some ways served as a trigger for the work that Loring and Aspen’s chief executive officer Dr. Howard Federoff would be bringing to market eight years later.
Other cell replacement therapies for Parkinson’s had run into difficulties because patient’s bodies would reject the introduction of foreign neurons — in much the same way that organ transplants are sometimes unsuccessful because a host rejects the foreign tissue.
Aspen’s technology uses the host’s own tissue to develop the stem cells that will become the basis for treatment. A patient who carries a diagnosis of Parkinsons would be consented to give a biopsy and the tissue collected is then placed in a cell culture. The cells are then converted into pluripotent stem cells through the introduction of an inert viral RNA that recodes the cell structure.
Those pluripotent stem cells are then converted into neurons that are then transplanted into a patient to replace the ones that Parkinson’s disease has destroyed.
Federoff and Loring have known each other for years, and when the former vice chancellor for health affairs at the University of California, Irvine heard what Loring and her team was working on he stepped down to join her company as chief executive.
Federoff previously founded MedGenesis Therapeutix, another privately held company working on a treatment for Parkinsons. “Much of what we do for Parkinsons and the extant gene therapy is stabilizing the disease,” says Federoff. “Cells of fibroblasts help to dial the clock back.”
The key is the use of autologous cells — those collected from the same individual that will receive the transplant, says Federoff.
Aspen’s novel approach was compelling enough to win the support of longtime healthcare investors including OrbiMed, ARCH Venture Partners, Frazier Healthcare Partners, Domain Associates, Section 32, and former Y Combinator President, Sam Altman.
Following the new round, Aspen is significantly expanding its board of directors to include Faheem Hasnain, the founder of Gossamer Bio who’s taking the chairman role at Aspen; Tom Daniel a venture partner at ARCH Ventures, and Peter Thompson, a partner at OrbiMed.
Aspen’s first product is currently undergoing investigational new drug (IND)-enabling studies for the treatment of sporadic forms of Parkinson disease, the company said. Its second product uses gene correction and neuron therapy to try to treat genetic forms of Parkinson disease.
According to the company, the financing will support the completion of all remaining investigational studies and FDA submission of the studies relating to the company’s lead product. In addition, the financing will support data collection from a Phase 1 clinical trial and the expansion into Phase 2 randomized studies.