Category Archives: Oregon Stem Cells

Michelle Johnson and Jeff Maginnis got word at her 20-week ultrasound that her developing baby was diagnosed with spina bifida.

DAMASCUS, Ore. An Oregon baby became the second person in the world to undergo a ground breaking surgery after he was diagnosed with spina bifida while still in the womb.

Tobi Maginnis, now 8 months old, was born happy and healthy thanks to the procedure by a team of doctors at the University of California, Davis.

At home in Damascus, Tobi Maginnis is all smiles and laughs.

"Even when we were in [the] NICU, he smiled and he would laugh in his sleep as a baby. Three days old, laughing in his sleep," said Michelle Johnson and Jeff Maginnis, Tobi's parents.

That joy extends to their entire family after a long journey to get to this point.

"Jeff and I met and I have a 13-year-old son and Jeff has a 6-year-old daughter and we decided we needed one more to complete our family," Johnson said.

But after Johnson's 20-week ultrasound last year, the couple learned some distressing news during a call with the radiologist.

"His voice was just trembling," Johnson said. "He says, 'I need to talk to you about your ultrasound.' And I knew something was wrong. He said 'There's some abnormalities. It appears to be spina bifida.'"

According to health experts, spina bifida occurs when spinal tissue fails to fuse properly during the early stages of pregnancy, leading to a range of lifelong cognitive, mobility, urinary and bowel disabilities. It affects 1,500 to 2,000 children in the U.S. each year.

"Just kind of shock," Maginnis said about learning of the diagnosis. "There's this very serious problem with your fetus, with your baby. What do you do? How do you react? How do you move forward?"

Because options in Oregon for fetal surgery were extremely limited, the couple had to look outside the state. This led them to UC Davis and a clinical trial that makes use of stem cells to treat spina bifida. The clinical trial, known formally as the CuRe Trial: Cellular Therapy for In Utero Repair of Myelomeningocele, is funded by the states stem cell agency, California Institute for Regenerative Medicine.

"I tell [Jeff] all the time, I would rather be in the CuRe trial than win the Powerball because of how rare and exclusive it is, and how life-changing it's been for our son."

After several screenings, interviews and acceptance into the trial, the couple moved down to California. She was the second patient to enroll in the trial.

"I think I was nervous, but I was also relieved knowing we're pursuing the best option for our baby," Johnson said.

Despite fears and concerns, with the help of a 40 person team, the surgery was a success. At 25 weeks gestation, Johnson had the landmark fetal surgery and stem cell procedure, where stem cells were placed directly on her fetuss spinal cord using a special patch to repair the spina bifida defect, according to UC Davis.

The couple spent the rest of the pregnancy in California, with a C-section scheduled at 36 weeks.

"They put the drape down and they held Tobi up. It was like Simba in the The Lion King. A Pride Rock moment," Johnson said. "And then Jeff said, 'It's a boy!' And that's how we found out Tobi was a boy."

Born February 1, 2022, Tobi is happy, healthy and full of personality.

"Tobi is the second baby in the entire world to receive stem cells during gestational surgery for spina bifida repair," Johnson said.

She praised the staff at UC Davis for their work and called them "talented."

"After 10 years of animal trials, to finally be able to do this on humans, this is exciting and I just hope it continues to become more available for all moms," Johnson said.

At this point, Tobi doesn't need any more procedures, but doctors will monitor his progress for several more years so the team can continue to assess the stem cell surgical procedure's safety and effectiveness.

Original post:
Oregon baby undergoes fetal surgery for spina bifida | kgw.com

Medical condition

Neuronal ceroid lipofuscinosis is the general name for a family of at least eight genetically separate neurodegenerative lysosomal storage diseases that result from excessive accumulation of lipopigments (lipofuscin) in the body's tissues.[1] These lipopigments are made up of fats and proteins. Their name comes from the word stem "lipo-", which is a variation on lipid, and from the term "pigment", used because the substances take on a greenish-yellow color when viewed under an ultraviolet light microscope. These lipofuscin materials build up in neuronal cells and many organs, including the liver, spleen, myocardium, and kidneys.

The classic characterization of the group of neurodegenerative, lysosomal storage disorders called the neuronal ceroid lipofuscinoses (NCLs) is through the progressive, permanent loss of motor and psychological ability with a severe intracellular accumulation of lipofuscins,[2][3] with the United States and Northern European populations having slightly higher frequency with an occurrence of one in 10,000.[4] Four classic diagnoses have received the most attention from researchers and the medical field, differentiated from one another by age of symptomatic onset, duration, early-onset manifestations such as blindness or seizures, and the forms which lipofuscin accumulation takes.[2]

In the early infantile variant of NCL (also called INCL or Santavuori-Haltia), probands appear normal at birth, but early visual loss leading to complete retinal blindness by the age of 2 years is the first indicator of the disease; by 3 years of age, a vegetative state is reached, and by 4 years, isoelectric encephalograms confirm brain death. Late infantile variant usually manifests between 2 and 4 years of age with seizures and deterioration of vision. The maximum age before death for late infantile variant is 1012 years.[5][6][7][8] Juvenile NCL (JNCL, Batten disease, or Spielmeyer-Vogt), with a prevalence of one in 100,000, usually arises between 4 and 10 years of age; the first symptoms include considerable vision loss due to retinal dystrophy, with seizures, psychological degeneration, and eventual death in the mid- to late 20s or 30s ensuing.[9] Adult variant NCL (ANCL or Kuf's disease) is less understood and generally manifests milder symptoms; however, while symptoms typically appear around 30 years of age, death usually occurs 10 years later.[1]

All the mutations that have been associated with this disease have been linked to genes involved with the neural synapses metabolism most commonly with the reuse of vesicle proteins.[citation needed]

Childhood NCLs are generally autosomal recessive disorders; that is, they occur only when a child inherits two copies of the defective gene, one from each parent. When both parents carry one defective gene, each of their children faces a one in four chance of developing NCL. At the same time, each child also faces a one in two chance of inheriting just one copy of the defective gene. Individuals who have only one defective gene are known as carriers, meaning they do not develop the disease, but they can pass the gene on to their own children. The most commonly identified mutations are in the CLN3 gene, which is located on the short arm of chromosome 16 (16p12.1). The normal function of the gene is not presently known, but results in a transmembrane protein.[citation needed]

Adult NCL may be inherited as an autosomal recessive (Kufs), or less often, as an autosomal dominant (Parry's) disorder. In autosomal dominant inheritance, all people who inherit a single copy of the disease gene develop the disease. As a result, no carriers of the gene are unaffected.[citation needed]

Many authorities refer to the NCLs collectively as Batten disease.[10]

Because vision loss is often an early sign, NCL may be first suspected during an eye exam. An eye doctor can detect a loss of cells within the eye that occurs in the three childhood forms of NCL. However, because such cell loss occurs in other eye diseases, the disorder cannot be diagnosed by this sign alone. Often, an eye specialist or other physician who suspects NCL may refer the child to a neurologist, a doctor who specializes in disease of the brain and nervous system. To diagnose NCL, the neurologist needs the patient's medical history and information from various laboratory tests.[citation needed]

Diagnostic tests used for NCLs include:

The older classification of NCL divided the condition into four types (CLN1, CLN2, CLN3, and CLN4) based upon age of onset, while newer classifications divide it by the associated gene.[11][12]

CLN4 (unlike CLN1, CLN2, and CLN3) has not been mapped to a specific gene.

Nonsense and frameshift mutations in the CLN1 gene (located at1p32[15][16][17]) always induce classical INCL, while some missense mutations have been associated with ANCL in addition to the infantile and juvenile forms. The mutation typically results in a deficient form of a lysosomal enzyme called palmitoyl protein thioesterase 1 (PPT1).[18]

The wild-type PPT1 is a 306-amino acid polypeptide that is typically targeted for transport into lysosomes by the mannose 6-phosphate (M6P) receptor-mediated pathway.[5][18] Here, the protein appears to function in removing palmitate residues by cleaving thioester linkages in s-acylated (or palmitoylated) proteins, encouraging their breakdown.[5][6] Defective polypeptides, however, are unable to exit the endoplasmic reticulum (ER), most likely due to misfolding; further analyses of this pathway could serve to categorize INCL among lysosomal enzyme deficiencies. The human PPT gene shows 91% similarity to bovine PPT and 85% similarity to rat PPT; these data indicate that the PPT gene is highly conserved and likely plays a vital role in cell metabolism.[5] In addition, buildup of defective PPT1 in the ER has been shown to cause the increased release of Ca2+. This homeostasis-altering event leads to increased mitochondrial membrane permeability and subsequent activation of caspase-9, eventually leading to an accumulation of cleft and uncleft poly(ADP-ribose) polymerase and eventual apoptosis.[6]

The CLN2 gene encodes a 46kDa protein called lysosomal tripeptidyl peptidase I (TPP1), which cleaves tripeptides from terminal amine groups of partially unfolded proteins.[7][19] Mutations of this gene typically result in a LINCL phenotype.[20]

On April 27, 2017, the U.S. Food and Drug Administration approved cerliponase alfa (Brineura) as the first specific treatment for NCL. It is enzyme replacement therapy manufactured through recombinant DNA technology. The active ingredient in Brineura, cerliponase alfa, is intended to slow loss of walking ability in symptomatic pediatric patients 3 years of age and older with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2), also known as TPP1 deficiency. Brineura is administered into the cerebrospinal fluid by infusion via a surgically implanted reservoir and catheter in the head (intraventricular access device).[21]

All mutations resulting in the juvenile variant of NCL have been shown to occur at the CLN3 gene on 16p12;[16] of the mutations known to cause JNCL, 85% result from a 1.02-kb deletion, with a loss of amino acids 154438, while the remaining 15% appear to result from either point or frameshift mutations.[9] The wild-type CLN3 gene codes for a protein with no known function,[3] but studies of the yeast CLN3 ortholog, the product of which is called battenin (after its apparent connections to Batten's disease, or JNCL), have suggested that the protein may play a role in lysosomal pH homeostasis. Furthermore, recent studies have also implied the protein's role in cathepsin D deficiency; the overexpression of the defective protein appears to have significant effects on cathepsin D processing, with implications suggesting that accumulation of ATP synthase subunit C would result.[22] Only recently have studies of human patients shown deficiency of lysosomal aspartyl proteinase cathepsin D.[citation needed]

Between 1.3 and 10% of cases are of the adult form. The age at onset is variable (662 yr). Two main clinical subtypes have been described: progressive myoclonus epilepsy (type A) and dementia with motor disturbances, such as cerebellar, extrapyramidal signs and dyskinesia (type B). Unlike the other NCLs, retinal degeneration is absent. Pathologically, the ceroid-lipofuscin accumulates mainly in neurons and contains subunit C of the mitochondrial ATP synthase.[citation needed]

Two independent families have been shown to have mutations in the DNAJC5 gene one with a transversion and the other with a deletion mutation.[23] The mutations occur in a cysteine-string domain, which is required for membrane targeting/binding, palmitoylation, and oligomerization of the encoded protein cysteine-string protein alpha (CSP). The mutations dramatically decrease the affinity of CSP for the membrane. A second report has also located this disease to this gene.[24]

Currently, no widely accepted treatment can cure, slow down, or halt the symptoms in the great majority of patients with NCL, but seizures may be controlled or reduced with use of antiepileptic drugs. Additionally, physical, speech, and occupational therapies may help affected patients retain functioning for as long as possible.[citation needed] Several experimental treatments are under investigation.[citation needed]

In 2001, a drug used to treat cystinosis, a rare genetic disease that can cause kidney failure if not treated, was reported to be useful in treating the infantile form of NCL. Preliminary results report the drug has completely cleared away storage material from the white blood cells of the first six patients, as well as slowing down the rapid neurodegeneration of infantile NCL.Currently, two drug trials are underway for infantile NCL, both using Cystagon.[citation needed]

A gene therapy trial using an adenoassociated virus vector called AAV2CUhCLN2 began in June 2004 in an attempt to treat the manifestations of late infantile NCL.[25] The trial was conducted by Weill Medical College of Cornell University[25] and sponsored by the Nathan's Battle Foundation.[26] In May 2008, the gene therapy given to the recipients reportedly was "safe, and that, on average, it significantly slowed the disease's progression during the 18-month follow-up period"[27] and "suggested that higher doses and a better delivery system may provide greater benefit".[28]

A second gene therapy trial for late infantile NCL using an adenoassociated virus derived from the rhesus macaque (a species of Old World monkey) called AAVrh.10 began in August 2010, and is once again being conducted by Weill Medical College of Cornell University.[28] Animal models of late infantile NCL showed that the AAVrh.10 delivery system "was much more effective, giving better spread of the gene product and improving survival greatly".[28]

A third gene therapy trial, using the same AAVrh.10 delivery system, began in 2011 and has been expanded to include late infantile NCL patients with moderate tosevere impairment or uncommon genotypes, and uses a novel administration method that reduces general anesthesia time by 50% to minimize potential adverse side effects.[29]

A painkiller available in several European countries, flupirtine, has been suggested to possibly slow down the progress of NCL,[30] particularly in the juvenile and late infantile forms. No trial has been officially supported in this venue, however. Currently, the drug is available to NCL families either from Germany, Duke University Medical Center in Durham, North Carolina, or the Hospital for Sick Children in Toronto.[citation needed]

On October 20, 2005, the Food and Drug Administration approved a phase-I clinical trial of neural stem cells to treat infantile and late infantile Batten disease. Subsequent approval from an independent review board also approved the stem cell therapy in early March 2006. This treatment will be the first transplant of fetal stem cells performed on humans. The therapy is being developed by Stem Cells Inc and is estimated to have six patients. The treatment was to be carried out in Oregon.[31]

Juvenile NCL has recently been listed on the Federal Clinical Trials website to test the effectiveness of bone-marrow or stem-cell transplants for this condition. A bone-marrow transplant has been attempted in the late infantile form of NCL with disappointing results; while the transplant may have slowed the onset of the disease, the child eventually developed the disease and died in 1998.[citation needed]

Trials testing the effectiveness of bone-marrow transplants for infantile NCL in Finland have also been disappointing, with only a slight slowing of disease reported.[32]

In late 2007, Dr. David Pearce et al. reported that Cellcept, an immunosuppressant medication commonly used in bone-marrow transplants, may be useful in slowing down the progress of juvenile NCL.[33]

On April 27, 2017, the U.S. FDA approved cerliponase alfa as the first specific treatment for NCL.[21]

Incidence can vary greatly from type-to-type, and from country-to-country.[34]

In Germany, one study reported an incidence of 1.28 per 100,000.[35]

A study in Italy reported an incidence of 0.56 per 100,000.[36]

A study in Norway reported an incidence of 3.9 per 100,000 using the years from 1978 to 1999, with a lower rate in earlier decades.[37]

The first probable instances of this condition were reported in 1826 in a Norwegian medical journal by Dr. Christian Stengel,[38][39][40][41] who described 4 affected siblings in a small mining community in Norway. Although no pathological studies were performed on these children the clinical descriptions are so succinct that the diagnosis of the Spielmeyer-Sjogren (juvenile) type is fully justified.[citation needed]

More fundamental observations were reported by F. E. Batten in 1903,[42] and by Heinrich Vogt in 1905,[43] who performed extensive clinicopathological studies on several families. Retrospectively, these papers disclose that the authors grouped together different types of the syndrome. Furthermore, Batten, at least for some time, insisted that the condition that he described was distinctly different from TaySachs disease, the prototype of a neuronal lysosomal disorder now identified as GM2 gangliosidosis type A. Around the same time, Walther Spielmeyer reported detailed studies on three siblings,[44] who have the Spielmeyer-Sjogren (juvenile) type, which led him to the very firm statement that this malady is not related to TaySachs disease. Subsequently, however, the pathomorphological studies of Kroly Schaffer made these authors change their minds to the extent that they reclassified their respective observations as variants of TaySachs disease, which caused confusion lasting about 50 years.[citation needed]

In 191314, Max Bielschowsky delineated the late infantile form of NCL.[45] However, all forms were still thought to belong in the group of "familial amaurotic idiocies", of which TaySachs was the prototype.

In 1931, Torsten Sjgren, a Swedish psychiatrist and geneticist, presented 115 cases with extensive clinical and genetic documentation and came to the conclusion that the disease now called the Spielmeyer-Sjogren (juvenile) type is genetically separate from TaySachs.[46]

Departing from the careful morphological observations of Spielmeyer, Hurst, and Sjovall and Ericsson, Zeman and Alpert made a determined effort to document the previously suggested pigmentary nature of the neuronal deposits in certain types of storage disorders.[47] Simultaneously, Terry and Korey[48] and Svennerholm[49] demonstrated a specific ultrastructure and biochemistry for TaySachs disease, and these developments led to the distinct identification and also separation of the NCLs from TaySachs disease by Zeman and Donahue. At that time, it was proposed that the late-infantile (JanskyBielschowsky), the juvenile (SpielmeyerVogt), and the adult form (Kufs) were quite different from TaySachs disease with respect to chemical pathology and ultrastructure and also different from other forms of sphingolipidoses.[citation needed]

Subsequently, Santavuori and Haltia showed that an infantile form of NCL exists,[50] which Zeman and Dyken had included with the Jansky Bielschowsky type.[citation needed]

See the article here:
Neuronal ceroid lipofuscinosis - Wikipedia

Nature, red in tooth and claw. According to Alfred Tennysons poem, In Memoriam A.H.H., that line describes Creations final law. Scholars say it captures the sometimes ruthless nature of well, nature. Tennysons assessment of existence is that survival is driven by competition, where the scrappy and the clever and the strong are the winners. The species that cant muster the ability to grab what they need, using tooth and claw if necessary, fall by the wayside.

Indeed, economists like Thomas Malthus saw the value of human struggle in driving progress. One can draw a line from that thinking to Charles Darwin and his On the Origin of Species, in which the power of that struggle instigates the development and differentiation of life on Earth.

Darwins theory of evolution is an example of how science can reflect the ideas of the time, says author Kristin Ohlson.

Ohlson turns that idea on its head, seeking out instead the collaborative elements of existence in her new book, Sweet in Tooth and Claw: Stories of Generosity and Cooperation in the Natural World, published Sept. 6 by Patagonia. In the present time, science has begun to illuminate the myriad connections and bonds that different forms of life have with each other and how critical they are to survival. Its cooperation thats responsible for the interlinkages of species firing off signals to each other in an otherwise quiet forest. Such mutually beneficial relationships are also responsible for the emergence of complex, eukaryotic cells, without which multicellular organisms wouldnt exist, she writes.

Through her visits with scientists, government officials and ranchers, Ohlson finds a metaphor in these partnerships for how we humans view our relationship with other lifeforms and each other. Perhaps following the example of the species around us and the way they work together could help us tackle vexing problems such as biodiversity loss and the changing climate, she muses.

Mongabays John Cannon spoke with Ohlson in August about the origins of the book and what she learned from writing it. This interview was lightly edited for length and clarity.

Mongabay: What prompted you to write this book? How did it get started?

Kristin Ohlson: I had written this other book called The Soil Will Save Us, and I got to meet all these scientists and farmers and ranchers who were trying to come up with an agriculture that actually heals landscapes. That was, of course, really exciting. One of the things that was so exciting for me about that book was understanding that plants have this relationship with the microorganisms in the soil. I didnt know that before. The official line that gets pumped out from industrial agriculture [companies] is that plants are just takers. Theyre just sucking up all the goodness out of the soil, all the nutrients and minerals, and thats why you need to keep buying their products to replenish those nutrients and minerals. But as it turns out, plants are givers as well as takers. That mutualistic relationship that plants have with the bacteria and the fungi and the protozoa and the little animals, that whole soil community, was one of the most exciting realizations from that book. So I wanted to build upon that.

Then, I went to a conference where Suzanne Simard was speaking. She was talking about her incredible research into how trees are connected by this underground network of fungi that ferry water and nutrients and chemical messages all through the forest, helping the forest at large be a resilient ecosystem. I sort of levitated in my seat and thought, oh, cooperation in nature. Thats what I want to write about.

Mongabay: Do you think science is moving in the direction of greater recognition of the importance of cooperation, as opposed to competition, in nature?

Kristin Ohlson: Its hard for me to be the one to say that were moving in that direction. [Ecologist] Judith Bronstein [edited] the standard text now on the standard, authoritative text on mutualism. I think she would probably say that research and perspective are growing. Unfortunately, one of the things that we all struggle with is that science has to be funded. Whos funding science? Its not the scientist. The funding is not [aimed] at understanding nature and helping humans adapt and work with nature. Its usually science that ultimately will fund products to have us hack nature. So who funds science is a big roadblock.

I do think that probably more of this science is growing. I mean, people around the world are talking about [Simards] work. Its almost like magic, in a way, right? We look at a forest, and theres all this stuff going on there. And we have no clue because we cant see with just our eyes. There are these powerful connections going on among living things.

Mongabay: Why do you think theres been so much emphasis on competition, the tooth and claw, in nature?

Kristin Ohlson: I think competition and conflict are naturally more interesting to us. We couldnt have thrived as living things for as long as we have without having an instinct to be on the lookout for danger. I think thats a big part of it. We naturally give our attention to things that seem threatening. We tend not to understand that cooperation is kind of the default. We have massive cities [that] couldnt function without massive amounts of cooperation at every level. But were only drawn to where that cooperation breaks down, where theres a gunfight or a robbery, or a building falling down.

Its the same way with our bodies [that are] built from special cells that were created by a mutualistic bond between ancient microorganisms. We are built from the floor up by these elements of cooperation. All these cells cooperate within our body, and the cells cooperate to form organs, and those organs cooperate with each other. We dont notice that because thats just the backdrop. We [only] notice when that cooperation breaks down. One of the scientists I interviewed talks about cancer as being a failure of cooperation.

Mongabay: In the book, you cover the discussion around competition and cooperation in nature and how it stretches back in history.

Kristin Ohlson: What really stands out for me is how much culture affects science and how much science affects culture. The ideas that we live with now mostly stem from Darwin and his colleagues. I was interested to find out that Darwin, as he developed the theory of evolution, was a product of the ideas of his time. Maybe just in the Western world, we have the idea of the lone genius, the person who just figures it all out all by himself or herself. But no, he was very much influenced by the ideas of Thomas Malthus, who was a wealthy pastor who argued that human reproduction would always outstrip resources and that the struggle over those resources and even death were good for society. When Darwin was casting around for a theory to make sense of all these observations he had made about the great diversity of life around us and the fossil records showing that there were life forms that no longer exist, he read Malthus and his ideas about progress through struggle. The thing that really stood out for me was how science can reflect the ideas of the time.

When I was researching, it took me a while to understand that what I was looking for was scientists studying mutually beneficial relationships between species. I found [ecologist Douglas] Bouchers book about mutualism back in the mid-80s. At the very beginning of his book, he said that, for a long time, mutualism had been sort of dismissed and wasnt an active area of study, but that was really changing, and there was a big return to that. I thought, wait a minute. What happened to that big return?

Mongabay: Did Bouchers book help lay the foundation for grappling with these concepts? You also mention biologist Lynn Margulis and her work on the origins of life and how it has diversified.

Kristin Ohlson: It laid some foundation. [Margulis] was castigated for years for her ideas that we are formed from this union between two microorganisms, and thats how our eukaryotic cells developed, and that those cells were able to form relationships with other cells, and then all the diversity of life that followed. [Margulis] was tough. She really persisted in pushing those ideas even though the culture of science was pushing back pretty hard.

Mongabay: How might our understanding of cooperation in the natural world inform our responses to these crises like climate change and the extinction of species?

Kristin Ohlson: One of the things thats important to realize is that we are part of the natural world. We have separated ourselves philosophically from the rest of nature, but that is a fools errand. We are part of the rest of nature, and we are, in fact, healthier, and our capabilities are enhanced when we have a connection with the natural world. What I hope people come away [from the book] with is realizing that we have to cooperate with the rest of nature instead of just saying were humans, and its a shame that other species cant make it while we thrive.

I wrote in the book about that stream in Oregon, where, back in 1957, somebody put a random stream through a culvert because they wanted to put a road over the top of it. And it turned out that the culvert completely disrupted salmon migration up that stream. The culvert was too high, and also, the water coming through the culvert came down at such an angle that it scoured the bottom of the creek and ruined the salmon spawning habitat on that side of the culvert. For 62 years, this culvert had prevented salmon and also Pacific lamprey from migrating up [the stream].

People could have said, what a shame, but we need that road, so were not going to change anything. But no. People studied exactly why this culvert was preventing that migration, and they changed it a couple of years ago. Theres a culvert now that the salmon and lamprey can move up. I think its 16 or 17 miles [26-27 kilometers] of the stream above that old culvert where there are now salmon and lamprey. In that case, people were saying, OK, we can have both. We can have the road, and we can have the salmon migration if we just figure out what the particulars are. Its not only a boon for the salmon and the lamprey theyre getting more and really nice habitat but [also for] all the creatures that feast upon the salmon and the lamprey. Then, as I found when I was doing the chapter about Suzanne Simards work, those salmon carcasses that those creatures take out of the river and eat part of and drop in the forests deliver a very specific form of nitrogen essential to forests flourishing.

Mongabay: Can you talk about the cooperative efforts of farmers and ranchers in Nevada working with scientists to restore wetlands in the U.S. state of Nevada?

Kristin Ohlson: That didnt start as an effort to rebuild wetlands in Nevada. It started with scientists and government agencies wanting to improve streams so that this one local trout could survive. To improve those local streams, they had to get some ranchers to change the way their cattle were managed. That part of the United States is an area where theres been huge friction between ranchers and government agencies and scientists for years. I think ranchers in that area generally felt under attack by a range of people who say that cattle ranching ruins landscapes, that [beef] is bad to eat.

Yet they are people who love the landscape, love the land [and] want to live in a thriving ecosystem. But it was hard for them to change their ways when these scientists and government agencies first got in touch with them. But they did start to make some changes in the way that they managed their cattle, mostly in terms of how much time the cattle could spend by these creeks. It was a not-insignificant change for the ranchers because it meant more work for them.

[But with] this small change of how they were managing their cattle, nature started to fill in those degraded sides of the creeks. Thats one of the things that I just loved about that story was that nature was ready with seeds that were already in the soil or that drifted in on the wind or that came from the animals that came to drink there. Vegetation started growing around the streams, and the ranchers were cheered somewhat by that.

Then, the beaver came in and just completely changed this landscape. The before-and-after pictures are just stunning. In the past, you see these same creeks that are just narrow and dry on all sides. [Today, there is] a completely different ecosystem coming up with all this riparian vegetation and big ponds that the beavers had built, which is bringing in wildlife, the actual water table around the creek started to change. It was just such an inspiring story, not only [of] the land changing, but of the relationship among the ranchers and the scientists and the government agency people changing. They all felt like it was such a triumph, even though they all had to change a little bit.

Mongabay: It is a really fascinating case. What other stories from the book stand out to you?

Kristin Ohlson: I just loved all the stories, and I loved doing the research. One of the stories that I just loved [and that] really became a kind of a guiding metaphor for me is at the end of the first chapter. I was talking to Katie McMahen, who was a colleague of Suzanne Simard and who is starting some new research to try to regenerate a landscape in Canada that had been ruined by a mine tailings [dam] flood. One of the things [McMahen] was doing was taking soil from the forest nearby that hadnt been ruined and putting handfuls [in the holes where] she was planting these new little trees out in this ruined landscape. She said, its ecosystem memories and legacies. Its little bits of DNA, its seeds, its little bits of fungi, fungal spores, bacterial spores, all these things that were part of that vibrant forest ecosystem, and were borrowing it to start new life there. I just love that idea that, even in really degraded landscapes, there are probably still some ecosystem memories and legacies. I really do like to extend that idea to the landscape of human relationships, and I believe that even now, especially in the United States, where things are so conflicted and [there is] so much political disagreement, that there are those legacies and memories that will help us evolve a more cooperative culture.

Banner image: Flowers and bees share one of the most well-known mutualistic relationships in nature. Image by Ralphs_Fotos via Pixabay (Public domain).

John Cannon is a staff features writer with Mongabay. Find himon Twitter: @johnccannon

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Examining cooperation in nature: Q&A with author Kristin Ohlson - Mongabay.com

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Taxanes, such as paclitaxel and docetaxel, cause severe and often permanent chemotherapy-induced hair loss (alopecia)

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ALRN-6924-induced cell cycle arrest protected hair follicles from paclitaxel-induced toxicity and irreversible stem cell damage

Ailerons precision medicine-based approach is designed to selectively protect normal, healthy cells from chemotherapy while ensuring chemotherapy cannot protect cancer cells

Ailerons ongoing non-small cell lung cancer (NSCLC) clinical trial and upcoming breast cancer clinical trial will evaluate ALRN-6924s protection against chemotherapy-induced bone marrow toxicities and other side effects, including alopecia

BOSTON, May 10, 2022 (GLOBE NEWSWIRE) -- Aileron Therapeutics (Nasdaq: ALRN), a chemoprotection oncology company that aspires to make chemotherapy safer and thereby more effective to save more patients lives, today announced a late-breaking oral presentation at the upcoming Society for Investigative Dermatology (SID) Annual Meeting, which will be held May 18 21, 2022 in Portland, Oregon. The presentation will highlight new non-clinical data developed in collaboration with Professor Ralf Paus, M.D., DSc, FRSB and his colleagues at the Dr. Phillip Frost Department of Dermatology & Cutaneous Surgery at the University of Miami Miller School of Medicine. This collaboration has generated promising ex vivo data demonstrating that ALRN-6924 protected human hair follicles and their stem cells from chemotherapy-induced acute and permanent damage. Details of the presentation are as follows:

Title:

ALRN-6924, a dual inhibitor of MDMX and MDM2, protects human scalp hair follicles and their epithelial stem cells from paclitaxel-induced toxicity (LB1018)

Presenter:

Jennifer Gherardini, Ph.D.; Paus Laboratory, University of Miami Miller School of Medicine

Date:

Thursday, May 19th

Time:

8:45 AM 11:15 AM PT

Session:

Late-Breaking Abstract Concurrent Session

Chemotherapy-induced toxicities range from severe and life-threatening to those that impact and diminish patients quality of life, sometimes long after chemotherapy has been completed. These toxicities occur because chemotherapy destroys normal, healthy cells while simultaneously destroying cancer cells, said Manuel Aivado, M.D., Ph.D., President and Chief Executive Officer at Aileron. Previously, we showed chemoprotection against severe bone marrow toxicities in small cell lung cancer patients receiving topotecan and demonstrated in healthy volunteers the mechanism of action cell cycle arrest underlying this chemoprotection benefit. We are excited to now present new data that may suggest ALRN-6924s ability to also protect against chemotherapy-induced hair loss, another devastating chemotherapy-induced side effect for millions of cancer patients.

Dr. Paus commented, These results got us quite excited as they directly follow in the footsteps of our prior work that showed arresting the cell cycle can have a strong protective effect against taxane-induced hair follicle damage. Until our research with ALRN-6924, we had not come across a cell cycle arrest-inducing drug that is in clinical testing for protection of normal cells without protecting cancer cells. Thus, ALRN-6924 invites a very promising and completely novel selective protection approach. In addition, we found that ALRN-6924 may exert some additional benefits that could reduce the risk of long-term damage of human hair follicle stem cells by taxanes.

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Aileron is currently developing ALRN-6924, a first-in-class MDM2/MDMX dual inhibitor, to selectively protect healthy cells in patients with cancers that harbor p53 mutations to reduce or eliminate chemotherapy-induced side effects while preserving chemotherapys attack on cancer cells. ALRN-6924 is designed to activate p53 in normal cells, which in turn upregulates p21, which pauses cell cycle in normal cells but not in p53-mutated cancer cells. The companys vision is to bring chemoprotection to all patients with p53-mutated cancer regardless of the type of cancer or chemotherapy.

About the Findings

Taxanes, such as paclitaxel and docetaxel, are known to cause severe and often permanent chemotherapy-induced alopecia. Over 90% of patients treated with this chemotherapy class experience alopecia, and approximately 10% (paclitaxel) to 25% (docetaxel) of patients experience permanent alopecia. Dr. Paus and his team previously demonstrated that paclitaxel damages human scalp hair follicles by inducing massive mitotic defects and apoptosis in hair matrix keratinocytes as well as bulge stem cell DNA damage, and that pharmacological induction of transient cell cycle arrest can protect hair follicles and stem cells (Purba et al. EMBO Molecular Medicine 2019). Aileron previously conducted in vitro studies showing that ALRN-6924 protected human fibroblasts in cell culture from multiple chemotherapies, but not p53-mutant breast cancer cells.

In the new non-clinical findings to be presented at the SID meeting, when organ-cultured anagen (i.e., active growth phase) scalp hair follicles from two human donors were pre-treated with ALRN-6924 or vehicle (i.e., placebo), followed by paclitaxel or vehicle, ALRN-6924 significantly increased the number of p21-positive hair matrix keratinocytes and bulge stem cells compared to vehicle or paclitaxel alone, confirming cell cycle arrest ex vivo. Further, pretreatment of paclitaxel-treated human hair follicles with ALRN-6924, led to a reduction in the number of melanin clumps, a marker of hair follicle cytotoxicity and dystrophy, as well as a reduction in apoptosis, pathological mitosis, and DNA damage. Aileron believes that these findings support clinical investigation of ALRN-6924 to prevent both acute and permanent chemotherapy-induced alopecia, in addition to its ongoing evaluation of ALRN-6924 to protect against chemotherapy-induced bone marrow and other toxicities.

About Ailerons Clinical Trials of ALRN-6924

Aileron is on track to initiate a Phase 1b randomized, controlled trial of ALRN-6924 in patients with p53-mutated ER+/HER2- neoadjuvant breast cancer in 2Q 2022. The planned breast cancer trial will evaluate ALRN-6924s protection against chemotherapy-induced bone marrow toxicities, as well as other toxicities, including alopecia, in patients with p53-mutated ER+/HER2- breast cancer treated with a doxorubicin plus cyclophosphamide and docetaxel chemotherapy regimen.

The company is currently enrolling patients in a Phase 1b randomized, double-blind, placebo-controlled trial evaluating ALRN-6924s protection against chemotherapy-induced bone marrow and other toxicities in patients with advanced p53-mutated non-small cell lung cancer undergoing treatment with first-line carboplatin plus pemetrexed with or without immunotherapy. While patients in this trial are monitored for alopecia, historically, only a small percentage of patients treated with carboplatin plus pemetrexed experience acute alopecia. Aileron is on track to report interim results on the first 20 patients enrolled in the NSCLC trial in June 2022 and topline results on 60 patients in 4Q 2022.

About Aileron Therapeutics

Aileron is a clinical stage chemoprotection oncology company that aspires to make chemotherapy safer and thereby more effective to save more patients lives. ALRN-6924, our first-in-class MDM2/MDMX dual inhibitor, is designed to activate p53, which in turn upregulates p21, a known inhibitor of the cell replication cycle. ALRN-6924 is the only reported chemoprotective agent in clinical development to employ a biomarker strategy, in which we exclusively focus on treating patients with p53-mutated cancers. Our targeted strategy is designed to selectively protect multiple healthy cell types throughout the body from chemotherapy without protecting cancer cells. As a result, healthy cells are spared from chemotherapeutic destruction while chemotherapy continues to kill cancer cells. By reducing or eliminating multiple chemotherapy-induced side effects, ALRN-6924 may improve patients quality of life and help them better tolerate chemotherapy. Enhanced tolerability may result in fewer dose reductions or delays of chemotherapy and the potential for improved efficacy.

Our vision is to bring chemoprotection to all patients with p53-mutated cancers, which represent approximately 50% of cancer patients, regardless of type of cancer or chemotherapy. Visit us at aileronrx.com to learn more.

Forward-Looking Statements

Statements in this press release about Ailerons future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, may constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements about the potential of ALRN-6924 as a chemoprotective agent, including its ability to prevent both acute and permanent chemotherapy-induced alopecia, and the Companys strategy and clinical development plans. The words anticipate, believe, continue, could, estimate, expect, intend, may, plan, potential, predict, project, should, target, would and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including whether Ailerons cash resources will be sufficient to fund its continuing operations for the periods anticipated or with respect to the matters anticipated; whether initial results of clinical trials will be indicative of final results of those trials or results obtained in future clinical trials, including trials in different indications; whether ALRN-6924 will advance through the clinical trial process on a timely basis, or at all; whether the results of such trials will be accepted by and warrant submission for approval from the United States Food and Drug Administration or equivalent foreign regulatory agencies; whether ALRN-6924 will receive approval from regulatory agencies on a timely basis or at all or in which territories or indications ALRN-6924 may receive approval; whether, if ALRN-6924 obtains approval, it will be successfully distributed and marketed; what impact the coronavirus pandemic may have on the timing of our clinical development, clinical supply and our operations; and other factors discussed in the Risk Factors section of Ailerons annual report on Form 10-K for the year ended December 31, 2021, filed on March 28, 2022, and risks described in other filings that Aileron may make with the Securities and Exchange Commission. Any forward-looking statements contained in this press release speak only as of the date hereof, and Aileron specifically disclaims any obligation to update any forward-looking statement, whether because of new information, future events or otherwise.

Investor Contact:Stern Investor RelationsAlexander Loboalex.lobo@sternir.com

Media Contact:Liz Melone617-256-6622

Link:
Aileron Therapeutics Announces Late-Breaking Oral Presentation of Non-Clinical Data Demonstrating ALRN-6924 Protected Human Hair Follicles and Their...

By Andy Coghlan

Stem cells are the cellular putty from which all tissues of the body are made. Ever since human embryonic stem cells were first grown in the lab, researchers have dreamed of using them to repair damaged tissue or create new organs, but such medical uses have also attracted controversy. Yesterday, the potential of stem cells to revolutionise medicine got a huge boost with news of an ultra-versatile kind of stem cell from adult mouse cells using a remarkably simple method. This timeline takes you through the ups and downs of the stem cell rollercoaster.

1981, Mouse beginningsMartin Evans of Cardiff University, UK, then at the University of Cambridge, is first to identify embryonic stem cells in mice.

1997, Dolly the sheepIan Wilmut and his colleagues at the Roslin Institute, Edinburgh unveil Dolly the sheep, the first artificial animal clone. The process involves fusing a sheep egg with an udder cell and implanting the resulting hybrids into a surrogate mother sheep. Researchers speculate that similar hybrids made by fusing human embryonic stem cells with adult cells from a particular person could be used to create genetically matched tissue and organs.

1998, Stem cells go humanJames Thomson of the University of Wisconsin in Madison and John Gearhart of Johns Hopkins University in Baltimore, respectively, isolate human embryonic stem cells and grow them in the lab.

2001, Bush controversyUS president George W. Bush limits federal funding of research on human embryonic stem cells because a human embryo is destroyed in the process. But Bush does allow continued research on human embryonic stem cells lines that were created before the restrictions were announced.

2005, Fraudulent clonesWoo Suk Hwang of Seoul National University in South Korea reports that his team has used therapeutic cloning a technique inspired by the one used to create Dolly to create human embryonic stem cells genetically matched to specific people. Later that year, his claims turn out to be false.

2006, Cells reprogrammedShinya Yamanaka of Kyoto University in Japan reveals a way of making embryonic-like cells from adult cells avoiding the need to destroy an embryo. His team reprograms ordinary adult cells by inserting four key genes forming induced pluripotent stem cells.

2007, Nobel prizeEvans shares the Nobel prize for medicine with Mario Capecchi and Oliver Smithies for work on genetics and embryonic stem cells.

2009, Obama-powerPresident Barack Obama lifts 2001 restrictions on federal funding for human embryonic stem cell research.

2010, Spinal injuryA person with spinal injury becomes the first to receive a medical treatment derived from human embryonic stem cells as part of a trial by Geron of Menlo Park, California, a pioneering company for human embryonic stem cell therapies.

2012, Blindness treatedHuman embryonic stem cells show medical promise in a treatment that eases blindness.

2012, Another NobelYamanaka wins a Nobel prize for creating induced pluripotent stem cells, which he shares with John Gurdon of the University of Cambridge.

2013, Therapeutic cloningShoukhrat Mitalipov at the Oregon National Primate Research Center in Beaverton and his colleagues produce human embryonic stem cells from fetal cells using therapeutic cloning the breakthrough falsely claimed in 2005.

2014, Pre-embryonic stateCharles Vacanti of Harvard Medical School together with Haruko Obokata at the Riken Center for Developmental Biology in Kobe, Japan, and colleagues announced a revolutionary discovery that any cell can potentially be rewound to a pre-embryonic state using a simple, 30-minute technique.

2014, Therapeutic cloning with adult cellsTeams led by Dieter Egli of the New York Stem Cell Foundation and Young Gie Chung from CHA University in Seoul, South Korea, independently produce human embryonic stem cells from adult cells, using therapeutic cloning. Eglis team use skin cells from a woman with diabetes and demonstrate that the resulting stem cells can be turned into insulin-producing beta cells. In theory, the cells could be used to replace those lost to the disease.

2014, Human trialsMasayo Takahashi at the same Riken centre is due to select patients for what promises to be the worlds first trial of a therapy based on induced pluripotent stem cells, to treat a form of age-related blindness.

More on these topics:

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Stem cell timeline: The history of a medical sensation ...

Turn up your hearing aid, will ya?

http://www.Shutterstock.com. Gene therapy, hearing loss.

As lewd and crude and rude as it sounds, it is the general response for the person on the street, even if muttered underneath his or her breath, when dealing with someonefriend, family, co-worker, etc.who suffers from mild to moderate hearing loss.

Aside from some surgical procedures that are not as commonly known, hearing deviceswhile being constantly upgraded in the digital agehave been the traditional source of help.

But there is one other ray of hope burgeoning on the horizon: Gene therapy.

From the Ivy League to the University of Miami to the University of Michigan to Oregon State to Tel Aviv, experts are on the verge of cracking the case.

Although not yet available, inner ear gene therapy for monogenic hearing loss is an emerging technology, explained Jeffrey R. Holt, PhD, a professor of Otolaryngology & Neurology at Harvard Medical School and of Boston Childrens -Hospital. There is growing interest from scientists, funding agencies, industry and patients, all spurred on by recent proof-of-concept studies showing recovery of auditory function in animal models of human hearing loss.

Holt added that genetic treatments for hearing loss sit on the horizon and the significance of this new therapeutic strategy for patients and families is high.

Nonetheless, he cautioned that the most common forms of genetic hearing loss, the result of mutations in GJB2, may be difficult to treat using gene therapy. Other rare forms of genetic hearing loss, due to mutations in OTOF, TMC1, or Usher syndrome, may be those first in line, but others will like follow.

Fan-Gang Zeng, PhD, the director of the Center of Hearing Research at the University of California-Irvine School of Medicine, explained that gene therapy addresses hearing loss biologically by repairing or restoring damaged cells, which hearing aids or cochlear implants do not accomplish.

Gene therapy is the future, but we dont know when the future will come, he said. While gene therapy is still in infancy, genetic screening of hearing loss is relatively matured. Concurrent screening with traditional audiological measures (OAE and ABR) and genetic testing can improve both the accuracy and prognosis of hearing loss while helping patients and doctors predict its course of development and management on an individual basis.

Yehoash Raphael, PhD, is a professor of Otolaryngology at the University of Michigans Kresge Research Institute. He has been recognized around the globe for his research, the interests of which include inner ear biology, protection and regeneration, gene therapy, genetic deafness, CHARGE Syndrome and stem cell therapy.

Raphael believes gene therapy should be advanced for several clinical conditions, both environmental and genetic.

At the cellular level, the goals would be related to repair and regeneration of cells that are injured or lost, he said. At present, amplification or cochlear implants provide an acceptable solution for many patients.

He cautioned, however, the biological therapy that restores function may work better, but is not currently available.

Ideally, we would like gene therapy to improve so it can be used for treating genetic deafness and sensorineural hearing loss caused by hair cell loss due to overstimulation, aminoglycosides, or infections, he said. As such, gene therapy presents an exciting prospect for future hearing restoration therapies.

At Michigan, Raphael and his colleagues are using combinatorial gene transfer methods to enhance the efficiency of new hair cells and are planning to enhance this approach and include other genes.

We are working on two mouse models for genetic inner ear disease, trying to better understand the biology of the mutation and also to design therapies, he said, adding that the research on therapies has met with mixed results.

Holts lab has focused on development of gene therapy for patients with mutations in TMC1 and for Usher syndrome patients.

We have remarkable data showing full recovery auditory function in some cases, he said. We are working with industry partners to bring these therapies into the clinic.

Meanwhile, in the private sector, companies such as Decibel Therapeutics are also seeking solutions.

According to Laurence Reid, PhD, it is simply a case of seeing the need and seeking to answer it.

The impact of significant hearing loss and balance disorders on individuals is profound and disrupts their connectivity with their human and physical environment, said Reid, the CEO of Decibel. We believe the inner ear represents an exciting new frontier for gene therapy, which will result in a pipeline of transformative medicines.

Reid added that the inner ear is an organ that is exquisitely suited to gene therapy. As such, the therapy can be delivered directly to the relevant cells, which are non-dividing and offer a durable potential for gene therapy. Lastly, the ear has a degree of immune privilege, which will moderate immune response against the therapy.

Said Reid, We are developing technologies that enable precision gene therapy, which will enable us to control the expression of the transgene in the gene therapy and limit the resulting pharmacology to precise cell types in which we intend to elicit a biological response.

Programs are in development to address both hearing loss and balance disorders and our therapies will comprise treatments for genetic forms of hearing loss, together with regenerative medicines, to treat acquired forms of hearing and balance disorders.

Looking ahead at the future of gene therapy as related to hearing loss, Raphael explained that the current technology for gene transfer for inner ear therapy needs to be improved in several cardinal and critical aspects to become a clinical reality.

He added that some of the parameters that need to be optimized include high cell-specificity, control of duration and extent of gene expression (how long and how much), acceptable route for delivering the vectors into the target site, and lack of toxicity and other side effects.

All these parameters are being addressed but still far from being accomplished, he said. Lack of accurate and reliable diagnostic tools, especially related to hair cell loss, also complicate the implementation of gene transfer technology.

Better technology would include upgraded batteries of tests that can predict the condition of the auditory epithelium, auditory nerve and other structures that are needed for biological hearing.

The promise of hearing restoration would become more realistic with these parameters resolved, he said.

Holt also cautioned against expected results tomorrow or the next day.

While hopes are high that this may soon be a therapeutic option for some patients with genetic hearing loss, it is important to keep in mind that a careful and systematic approach will be required to fully understand both the safety and efficacy of this treatment modality, he said. There are at least 100 forms of genetic hearing loss and each will need to be evaluated before use in patients can commence.

Reid further explained the importance of expanding access to genetic testing so families can understand the roots of their childs congenital hearing loss and seek out relevant clinical trials and ultimately tailored therapies.

Noting that accurate diagnosis of infant hearing loss is crucial to developing new treatments and providing clinical care, Reid added that Decibel hasin collaboration with Invitaelaunched Amplify, a sponsored testing program in the U.S. and Australia.

This program provides genetic testing at no charge for children with auditory neuropathy and aims to drive awareness of genetic testing and gain physician interest, as well as support enrollment into future clinical trials, he said.

What does all this mean for audiology professionals?

Holt predicts that audiologists will be an important part of the hearing health care team as this new wave of therapeutic options enters clinical trials, eventually wins approval, and becomes more broadly available.

He added that evaluation of auditory function before and after gene therapy treatments will be critical for understanding the efficacy, durability, and therapeutic window for hearing preservation and restoration.

In preparation for the coming wave, audiologists can understand basic genetics, familiarize themselves with the various genes associated with genetic hearing loss, and be prepared to field patient questions, he said. I suspect that as soon as the first inner ear gene therapies enter clinical trials, there will be an explosion of patient interest and inquiries. However, inner ear gene therapies will not be a magic bullet cure-all. Rather, a precision medicine approach will be required, as these therapies will need to be tailored to each patients specific genetic diagnosis.

Zeng had a similar view and explained that future audiologists will need to learn and understand the genetic component of hearing loss, which contributes half or more to the prevalence of hearing loss.

Dont expect gene therapy to be a silver bullet that can solve all the problems, said Zeng. There are a lot of things that gene therapy cannot solve (i.e., hearing loss related to mental issues).

Raphael made the distinction between audiologists doing research and clinicians, advising those in research to consider joining the research efforts to design diagnostic means that will determine presence/absence of hair cells and/or neurons, and if hair cells are absent, where in the cochlea this condition exists and what state the supporting cells are in.

He added: Are they differentiated or flat? The condition of supporting cells is an important factor in planning the set of genes that will be used to generate new hair cells.

Raphael explained that audiologists in the clinics need to be aware that there are currently no therapies based on gene transfer being offered. In some cases of genetic hearing loss, when the diagnosis is clear and the gene involved is not a very large gene, there is a chance that gene therapy could be offered in the relatively near future.

He added that this is especially true for mutations that affect hair cell, and where the hair cells survive but do not function properly.

I have a feeling that many of the patients asking about gene therapy options are those experiencing age-related hearing loss, which most of us are likely to develop at different speeds of progression, he said. Because many of these cases have long-term loss of hair cells and likely at least some neuronal regression or degeneration, the application of gene therapy would be very complex and challenging.

Reid added that, over the next several years, Decibel hopes that a range of pharmaceutical interventions will become available to people with hearing loss and their caregivers.

Audiologists will thus have therapeutic options in addition to the existing devices, which assist hearing improvement, he said. Diagnosis of particular forms of hearing loss will expand to include broader consideration of genetic mutations responsible for hearing loss.

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Gene Therapy for Hearing Loss on the Horizon : The Hearing Journal - LWW Journals

The elements that constitute longevity have long eluded medical circles worldwide. But it is clearer than ever that evading illness is key. Antioxidants boast life-prolonging effects because they rid the body of harmful substances. But some antioxidants, such as those found in green tea are more potent than others.

Green tea is an excellent source of catechins, a potent antioxidant revered for its protective effects against disease.

Researchers believe that the compounds are responsible for the beverages cholesterol-lowering effects, explains the AARP.

The specific type of catechins found in green tea is ECGC, which is renowned as being one of the most potent.

One meta-analysis published in the American Journal of Clinical Nutrition suggested that green tea significantly reduces total cholesterol, including LDL or bad cholesterol.

READ MORE: How to live longer: The cholesterol-lowering drink that significantly boosts longevity

A host of studies have also highlighted the life-prolonging effects of ECGC, explaining it may add more than a year of disease-free life.

In one study performed on rodents, researchers split the young adult mice into three groups to observe the protective effects underpinning ECGC.

One group served as controls and were offered a standard lab chow diet alongside plain water.

Another group ate high-fat diets and drank water spiked with fructose, while the third group ate the same diet accompanied with water laced with EGCG.

DONT MISS:

Results later revealed that rodents that consumed ECGC performed better in cognitive tests, confirming the neuroprotective effects of the compound.

A filled cup of brewed green contains around 50 to 100 mg of ECGC.

Green tea contains the highest concentrations of the compound, which increases with brewing time.

Separate studies conducted at Oregon State University have suggested the compound has the ability to increase the bodys number of regulatory T cells, which may help protect against autoimmune diseases.

Researchers found the compound was able to regulate appetite among the rodents following a high fat and high sugar diet.

In 2020, a study conducted on over 100,000 Chinese participants found those who drank green tea more than three times a week, lived on average 15 months longer than those who did.

The others of the study wrote: Habitual tea drinks had 1.41 years longer of cardiovascular disease-free years and 1.26 years longer of life expectancy at the index age of 50.

Tea consumption was associated with reduced risks of atherosclerotic cardiovascular disease and all-cause mortality, especially among those consistent habitual tea drinks.

EGCG is known to aid with inflammation, weight loss, and prevent heart and brain disease, but it is not the only beneficial compound found in green tea.

Tea also contains theanine, an amino acid that can relieve stress, and arginine, which also has a relaxing effect.

The stress-reducing effect of thiamine and green tea is thought to contribute to the maintenance of mental health and the control of brain ageing in many people, wrote the authors of one study published in the journal Molecules.

In doing so, green tea suppresses brain ageing through the activity of nerve cells by both EGCG and its degradation products, and the reductions in stress achieved by thiamine and arginine.

Data highlighting the life-prolonging effects of green tea stem from observational studies to date, so no causal relationship has yet been confirmed.

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How to live longer: Green tea may halt brain decline and prolong life - Toys Matrix

Thick smoke from wildfires blankets the area as a woman sits on a paddleboard on Okanagan Lake, in Lake Country, B.C., on Friday, August 13, 2021. Environment Canada has issued a heat warning and an air quality statement for much of the British Columbia coast and interior. THE CANADIAN PRESS/Darryl Dyck

DARRYL DYCK/The Canadian Press

Regions in British Columbia most affected by wildfires are currently reporting more COVID-19 cases per capita than most areas in the country, and some researchers suggest the fires could be driving case numbers.

Interior Health, the region comprising Okanagan, Kelowna and Kamloops, is doubling the four other B.C. health authorities in COVID-19 cases this month for the first time since the start of the pandemic. The south-central region is among the least vaccinated and the one that has suffered the majority of destruction from this years wildfires.

On Aug. 20, B.C. Health Officer Dr. Bonnie Henry announced added public health measures for the area to curb the spread, including mandatory masking in all indoor settings, a ban on high-intensity indoor group exercise, and capping outdoor gatherings at 50.

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The B.C. Health Ministry said the recent sharp increases in COVID-19 cases in the region have more to do with the spread of the highly transmissible Delta variant and remaining pockets of unvaccinated people than with exposure to wildfire smoke.

But a recent study from Harvard has raised the possibility that there could be a link. Even if there isnt, researchers and Dr. Henry say the fires are exacerbating local COVID-19 cases. The Ministry has warned residents that wildfire smoke can irritate the lungs, affect the immune system, and make one more prone to lung infections and viruses.

B.C. is living through one of the worst wildfire seasons of its history. Since April 1, 859,000 hectares of land have burned; more than twice the yearly provincial average, and area-wise equivalent to 15 cities of Toronto. The damage is concentrated inside B.C. Interior region, but smoke from the fires has darkened the skies of Central Alberta, prompting air quality warnings in Calgary and Edmonton this summer. Currently, the three provinces with the highest COVID-19 cases per capita are Alberta, B.C. and Saskatchewan, in that order.

Fires have also been an issue further east. In July, smoke from wildfires burning in Northwestern Ontario and Northern Manitoba travelled all the way to major cities such as Montreal, Fredericton and Winnipeg and Toronto. At one point, downtown Toronto logged the highest air pollution figure recorded since the air quality station started reporting in 2003.

The Harvard study, published earlier this month, found strong evidence that particulate matter called PM2.5 coming from wildfire smoke led to a surge in COVID-19 cases and deaths in 2020 in California, Washington and Oregon.

The particles can induce inflammation in lung cells, and can worsen respiratory conditions such as pneumonia, asthma and bronchitis. The researchers found that wherever particulate matter rose for a 28-day period to the concentration much of B.C. has recently experienced, COVID-19 cases increased by 11 per cent and deaths by almost nine per cent.

Since we know this association exists, we would like to see more action taken from our respective governments to improve wildfire management, try to stem climate change, said Dr. Kevin Josey, one of the studys authors and a Harvard Postdoctoral Research Fellow in Biostatistics.

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Wildfires have been especially destructive in the Western United States this year, but Dr. Josey said it is reasonable to expect similar associations between PM2.5 particle concentration and COVID-19 cases and deaths in British Columbia.

He said the correlation between wildfires and COVID-19 cases could be due to several factors beyond the fact that both can wage war with the respiratory system. Exposure to fire smoke could make asymptomatic people develop symptoms, resulting in regions registering more cases. Poor air quality could also be forcing people to gather indoors instead of out, creating more high-risk situations for transmission. A higher concentration of PM 2.5 particles could also create thicker air, and could allow the virus to travel farther and infect more people in close quarters.

Dr. Michael Mehta, an environmental scientist and professor at Thompson Rivers University in Kamloops, said the similarity in symptoms from COVID-19 infection and wildfire exposure could also make it more difficult to identify outbreaks in areas exposed to wildfires.

People dont know whether to get tested or isolate because lots of symptoms are the same: coughing, breathing issues, sore throat.

Dr. Mehta said he does not expect the wildfires to attenuate until the winter. Until then, he is afraid for the health of children under 12 who are still ineligible to be immunized, and tend to be vulnerable to fire smoke.

Children are unvaccinated and most likely to suffer consequences of air pollution because they still have developing lungs, and are most likely to be outside and active, he said. I think this combination can be quite devastating.

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For as long as the fire season continues and as cases remain up, Dr. Mehta implores residents to wear proper N95 masks as much as possible, procure a high-efficiency particulate air filter for their home and get immunized as soon as possible.

The case for vaccination has never been stronger.

Dr. Christopher Carlsten, the Canada Research Chair in Occupational and Environmental Lung Disease at the University of British Columbia, agrees that the fires probably are not helping to quell the fourth wave. He said all past literature would point to the correlation between PM 2.5 and COVID-19 being a strong possibility, and that even people from neighbouring provinces should take caution.

In Alberta, where the wildfire situation is comparatively better than in B.C. and well below the average in terms of land burned, smoke has been a constant problem for the past two months. Calgary imposed a fire ban in late July not due to the fire risk, but rather because officials did not want backyard fires to worsen the already dangerous air quality.

Yet Dr. Carlsten was cautious about drawing conclusions linking wildfires and COVID-19. The research can be easy to misinterpret, he said, because it does not compare between individuals, but rather between groups, whose COVID-19 numbers could vary from each other for several reasons.

There are many things that are potentially driving this association, he said, for example differences in public health measures between regions.

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Dr. Carlsten said the Harvard study is not enough for authorities to conclude that wildfires are the cause for the surge in COVID-19 cases in B.C. Still, he added, it would be wise for residents to take their own precautions.

I think its reasonable to take some action on this even though its not totally proven.

We want to be smart about exposure to fire smoke and exposure to COVID, and being smart about both of them at the same time seems to have little downside.

We have a weekly Western Canada newsletter written by our B.C. and Alberta bureau chiefs, providing a comprehensive package of the news you need to know about the region and its place in the issues facing Canada. Sign up today.

Originally posted here:
Harvard study links exposure to wildfire smoke and COVID-19 with implications for BC - The Globe and Mail

Researchers are using cell tracking technology to uncover how diseases, like cancer, progress

PORTLAND, Ore. Each year, almost two million people will be diagnosed with cancer.

Researchers are trying to find news ways to track how cancers will grow, spread, and mutate.

One single cell can provide a slew of information on what's happening in the body.

"It allows us to actually isolate specific regions within a tumor and explore what are the various different cell types within those regions of the tumor because tumors have a lot of different cells doing a lot of different things," said Andrew Adey, Associate Professor at Oregon Health & Science University

The technique also allows the researchers to track where the cells are coming from so researchers can see how diseases progress and alter healthy tissue.

"That could lead to potential novel targets that could be used to develop drugs to specifically target those specific alterations that occur," Adey added.

It makes it possible to watch the disease at the molecular level and create a precise treatment for more personalized care.

Professor Adey says that this cell-tracking technique would be useful for other diseases besides cancer, including neurological diseases and diseases that affect the heart and blood vessel.

"With this newest technology, what we've been able to do is instead of just isolating these cells from a large piece of tissue, we can actually track where these cells are present within the tissue," Adey explained.

Non-invasive tracking of immune and stem cells were primarily intended for potential cancer therapy applications while tracking of cancer cells could further our understanding of cancer development and tumor metastasis.

"So, it gives us a really precise mapping of where these cells are derived from within that piece of tissue, which can give us insights into a lot of disease states where there's actually a spatial component."

Cell-based therapy holds great promise and has long been on the horizon of cancer treatment. Cell-based therapies offer the ability to non-invasively track the delivery of various therapeutic cells, like T cells and stem cells, to the tumor site, and if or how they spread.

But it's not just cancers.

"One of the things that we applied this technology to was in stroke, where there's a very strong spatial component at the site of the injury and then radiating out from it," said Adey.

"We're able to actually capture that spatial information radiating out from that site of injury with all of the different cell types that are present and how those are altered in different ways with relation to the injury site and the spatial position, he added.

Safety is a high concern for researchers in future clinical applications and the ideal imaging modality for tracking therapeutic cells in cancer patients requires the imaging tags to be non-toxic, biocompatible, and highly specific.

If this story has impacted your life or prompted you or someone you know to seek or change treatments, please let us know by contacting Jim Mertens at jim.mertens@wqad.comor Marjorie Bekaert Thomas at mthomas@ivanhoe.com.

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YOUR HEALTH: Finding cures by tracking cells - WQAD.com

The 2017 Amtrak 501 train derailment demonstrated that when it comes to emergency needs, the Pacific Northwest blood supply needs to be stocked and at the ready community ready.

Governors Kate Brown and Jay Inslee have recognized this coming Saturday, Dec. 18, 2020 as Washington and Oregon Blood Donor Day in recognition of the donors who stepped up before and after the accident.

Bloodworks Northwest is inviting the community to take part by donating a pint of blood at centers or pop-up blood drives across the region to commemorate the vital role local donors play in emergency readiness. All donors who give on Dec. 18 will each receive a special pin.

Having blood on the shelves is essential when unforeseeable emergencies or tragedies happen.

The 2017 Amtrak train tragic event demonstrated that when it comes to patient needs, theres no such thing as a holiday. Demand for blood is continuous to support local patients having surgeries, trauma care and organ transplants as well as patients needing blood for cancer treatment. It typically takes 1,000 donors to meet community need. This month, Bloodworks needs an additional 300 donors a week to keep up with hospital requests for blood. Not sure whether youre eligible to donate blood? There are some basic qualifications to donatetypically youll need to be at least 18, at least 110 pounds and in good health. But many other factors, like travel, tattoos, and vaccinations people think might disqualify them arent true.

Our mission calls on all of us our community to be prepared and ready for anything, said Bloodworks President and CEO Curt Bailey. Hospitals need donors to keep donating throughout the winter season and to make it a lifesaving habit.

Donating blood in December is also an important step in learning if you have Sars-CoV-2 (COVID- 19) antibodies. Thats because Bloodworks is testing all donations for COVID-19 antibodies to help donors learn if they have the antibodies powerful in helping critically ill coronavirus patients through convalescent plasma donation.

About December 18, 2017On December 18, 2017 the Amtrak 501 passenger train heading from Seattle to Portland tragically derailed, prompting immediate action by first responders to aid everyone aboard the train. The injured passengers would be transported to local hospitals, and cared for with 150 blood donations made by our community. The care provided was only possible because Bloodworks shelves were stocked, weeks prior, with enough blood. The accident underscores the necessity for the community to be prepared for the next local emergency.

About December 18, 2020

Additional Resources:For the latest information on COVID-19 please visit the CDC website, Washington State Department of Health COVID-19 main page, and Oregon Health Authority.

Bloodworks Donor Centers and Pop-Up Centers:Appointments and information at BloodworksNW.org or 800-398-7888. See our list of Donor Centers and Pop-Up locations.

Test results will indicate if a persons immune system has produced antibodies to the virus, regardless of whether you ever showed symptoms. Information at bloodworksnw.org.

About Bloodworks NorthwestBloodworks Northwest is backed by 75 years of Northwest history and 250,000 donors. It is local, nonprofit, independent, volunteer-supported and community-based. A recognized leader in transfusion medicine, Bloodworks serves patients at hospitals in Washington, Oregon and Alaska partnering closely with local hospitals to deliver the highest level of patient care. Comprehensive services include blood components, complex cross-matching, specialized lab services for organ transplants, care for patients with blood disorders, and collection of cord blood stem cells for cancer treatment. Bloodworks Research Institute performs leading-edge research in blood biology, transfusion medicine, blood storage and treatment of blood disorders. Patients with traumatic injuries, undergoing surgeries or organ transplantation, or receiving treatment for cancer and blood disorders all depend on our services, expertise, laboratories and research. Blood donation appointments can be scheduled at bloodworksnw.org.

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2017 Amtrak tragedy becomes call-to-action for Blood Donor Day this Sat., Dec. 18 - ilovekent.net