Category Archives: Genetic Medicine

Growing up in Tanzania, I knew that fruit trees were useful. Climbing a mango tree to pick a fruit was a common thing to do when I was hungry, even though at times there were unintended consequences. My failure to resist consuming unripened fruit, for example, caused my stomach to hurt. With such incidents becoming frequent, it was helpful to learn from my mother that consuming the leaves of a particular plant helped alleviate my stomach pain.

This lesson helped me appreciate the medicinal value of plants. However, I also witnessed my family and neighboring farmers clearing the land by slashing and burning unwanted trees and shrubs, seemingly unaware of their medicinal value, to create space for food crops.

But this lack of appreciation for the medicinal value of plants extends beyond my childhood community. As fires continue to burn in the Amazon and land is cleared for agriculture, most of the concerns have focused on the drop in global oxygen production if swaths of the forests disappear. But Im also worried about the loss of potential medicines that are plentiful in forests and have not yet been discovered. Plants and humans also share many genes, so it may be possible to test various medicines in plants, providing a new strategy for drug testing.

As a plant physiologist, I am interested in plant biodiversity because of the potential to develop more resilient and nutritious crops. I am also interested in plant biodiversity because of its contribution to human health. About 80% of the world population relies on compounds derived from plants for medicines to treat various ailments, such as malaria and cancer, and to suppress pain.

Future medicines may come from plants

One of the greatest challenges in fighting diseases is the emergence of drug resistance that renders treatment ineffective. Physicians have observed drug resistance in the fight against malaria, cancer, tuberculosis and fungal infections. It is likely that drug resistance will emerge with other diseases, forcing researchers to find new medicines.

Plants are a rich source of new and diverse compounds that may prove to have medicinal properties or serve as building blocks for new drugs. And, as tropical rainforests are the largest reservoir of diverse species of plants, preserving biodiversity in tropical forests is important to ensure the supply of medicines of the future.

Plants and new cholesterol-lowering medicines

The goal of my own research is to understand how plants control the production of biochemical compounds called sterols. Humans produce one sterol, called cholesterol, which has functions including formation of testosterone and progesterone - hormones essential for normal body function. By contrast, plants produce a diverse array of sterols, including sitosterol, stigmasterol, campesterol, and cholesterol. These sterols are used for plant growth and defense against stress but also serve as precursors to medicinal compounds such as those found in the Indian Ayurvedic medicinal plant, ashwagandha.

Humans produce cholesterol through a string of genes, and some of these genes produce proteins that are the target of medicines for treating high cholesterol. Plants also use this collection of genes to make their sterols. In fact, the sterol production systems in plants and humans are so similar that medicines used to treat high cholesterol in people also block sterol production in plant cells.

I am fascinated by the similarities between how humans and plants manufacture sterols, because identifying new medicines that block sterol production in plants might lead to medicines to treat high cholesterol in humans.

New medicines for chronic and pandemic diseases

An example of a gene with medical implications that is present in both plants and humans is NPC1, which controls the transport of cholesterol. However, the protein made by the NPC1 gene is also the doorway through which the Ebola virus infects cells. Since plants contain NPC1 genes, they represent potential systems for developing and testing new medicines to block Ebola.

This will involve identifying new chemical compounds that interfere with plant NPC1. This can be done by extracting chemical compounds from plants and testing whether they can effectively prevent the Ebola virus from infecting cells.

There are many conditions that might benefit from plant research, including high cholesterol, cancer and even infectious diseases such as Ebola, all of which have significant global impact. To treat high cholesterol, medicines called statins are used. Statins may also help to fight cancer. However, not all patients tolerate statins, which means that alternative therapies must be developed.

Tropical rainforests are medicine reservoirs

The need for new medicines to combat heart disease and cancer is dire. A rich and diverse source of chemicals can be found in natural plant products. With knowledge of genes and enzymes that make medicinal compounds in native plant species, scientists can apply genetic engineering approaches to increase their production in a sustainable manner.

Tropical rainforests house vast biodiversity of plants, but this diversity faces significant threat from human activity.

To help students in my genetics and biotechnology class appreciate the value of plants in medical research, I refer to findings from my research on plant sterols. My goal is to help them recognize that many cellular processes are similar between plants and humans. My hope is that, by learning that plants and animals share similar genes and metabolic pathways with health implications, my students will value plants as a source of medicines and become advocates for preservation of plant biodiversity.

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Walter Suza, Adjunct Assistant Professor of Agronomy, Iowa State University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Image: Reuters

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The Medicine Plant That Could Have Changed the World. - The National Interest Online

After reading Christina Adamss new book Camel Crazy: A Quest for Miracles in the Mysterious World of Camels(New World Library), I may have a new favorite animal (sorry, cats and hippos).

Most of us know camels as curiosities at zoos. As beasts of burden highly adapted to hot and dry climates, theyve served the trade routes that helped build civilizations, and may indeed flourish in our increasingly hot and dry world. We value their hide, meat, and especially their milk.

Camels are unusual, biologically speaking. And that may be why their milk can alleviate some aspects of autism.

Camel milk sounds weird to American ears, but camels are a domestic fact of life elsewhere. Although the US classifies them as exotic animals, they actually have early origins here; fossils have been found in Los Angeles. But the true reservoir of knowledge on camels is found in rural cultures and universities in the Middle East, Asia, and Africa, Christina told me.

Got Camel Milk?

In 2005, Christina met a camel at a childrens book fair in Orange County CA. Rather than hauling kids around, the animal was standing near a display of lotions and soaps made with camel milk. When the owner started to tell Christina how the milk is hypoallergenic and helps premature babies in the Middle East, she glanced over at 7-year-old Jonah. Hed already had four years of costly treatments for autism.

Might it help reboot my sons immune system and help his autism symptoms? she recalls thinking, aware of a link to immune dysfunction. Cow milk and cheese made him hand-flap and walk in circles, which he described as feeling like having dirt in my brain. Vegan substitutes like rice, nut, or soy increased his allergic response.

Camel Crazy details Christinas two-year journey to find the milk. Once she started giving it to Jonah, four ounces at a time, mixed in with food like cereal, his behavior changed quickly.

He became calm. Inquisitive. Caring. His language became more emotional and focused. He held his head straight instead of rolling it. Eating became neat, not a mess fest. He dressed himself and began making eye contact. He even got his shoes and backpack on and was calmer in the car going to school.

By the third dose, Jonah was sleeping through the night. He became more fluid, social, and attuned. Within days he could cross the street without me holding on to him. Within weeks his skin grew smoother. The milk also reversed his skin irritation, agitation, mental distraction, hyperactivity, and stomach pain, Christina recalled.

So she did research and spread the word, first in an article Got Camel Milk? that went viral, then in a peer-reviewed case report, Autism Spectrum Disorder Treated With Camel Milk, published in Global Advances in Health and Medicine. After describing Jonahs early difficulties, she wrote on October 10, 2007, two weeks before my sons tenth birthday, he drank his first half cup (4 oz) of thawed raw unheated camel milk. The case report documents Jonahs sustained symptom improvements associated with drinking half a cup a day from 2007 to 2013.

Christina then began traveling the world, giving presentations on camel milk and autism, and consulting with scientists and vets. Camel Crazy details her immersion into the world of camels and cameleers, from Tuareg, Amish and Somali people in America to herders in India, Dubai and Abu Dhabi. She serves on the editorial board of the new International Journal of Camel Science.

I was a beta reader for Camel Crazyand loved it. Being a nerd I searched for the science, and wasnt disappointed. The milk indeed has some startling differences from other milks, yet tastes, Christina says, like cows milk.

Camels drink a lot, pee a little, exhale minimal vapor, have insulating coats, and their red blood cells balloon and shrink as the water content in the bloodstream shifts. Natural selection has favored persistence of these traits that provide adaptation to heat, aridity, and exposure to intense ultraviolet radiation and choking dust. Body temperature ranges from 93.2-104F (3440C).

Being specifically a genetics nerd, I delved deeper into the DNA that encodes the unusual versions of proteins that might explain the magic of camel milk, as well as other details of the physiology. Much of the info below comes from the article Desert to Medicine: A Review of Camel Genomics and Therapeutic Products, from three researchers at United Arab Emirates University.

Fighting an Opioid Released from Casein Breakdown

The first technical paper Christina found was The etiology of autism and camel milk as therapy, from Ben Gurion University researchers Reuven Yagil and Yosef Shabo. Parent reports inspired their work.

They zeroed in on an opiate-like effect. Casein, the most abundant milk protein, breaks down into peptide pieces. And one of them, beta-casomorphin-7, is an opioid. It can slip through the leaky gut of a person with autism and enter the brain. Could an opiate bathing the brain affect social interactions and lack of interest in surroundings?

Other breakdown peptides of casein (-casein and no -lactoglobulin), which are more abundant in cows milk, may spike milk allergies.

Upping Anti-Oxidants

Camel milk delivers potent anti-oxidants that might temper autism symptoms, wrote King Saud University researchers Laila Al-Ayadhi and Nadra Elyass Elamin in a2013 report. People with autism are more sensitive to oxidative stress, which is damage from unstable forms of oxygen called oxygen free radicals.

The researchers measured levels of three anti-oxidants in the blood of 60 kids with autism: superoxide dismutase, myeloperoxidase, and an enzyme needed to make glutathione. Over a two-week period, 24 children drank raw camel milk, 25 drank boiled camel milk, and 11 drank cows milk. The trial was double-blinded and randomized, but it wasnt a crossover, in which each child would have had all three milk experiences. Nevertheless, raw camel milk was superior in anti-oxidant levels and a behavioral rating scale.

Special Tiny Antibodies

Camels share with only their camelid brethren (llamas, alpacas, vicunas, and guanacos) tiny antibodies in milk, called nanobodies. Most antibodies have one or more Y-shaped subunits; a nanobody is one arm of one Y, the variable region that distinguishes species. A student discoveredcamel nanobodies in a lab course at the University of Brussels in 1993, analyzing a dromedarys blood serum. Camels make large antibodies too.

Nanobodies can squeeze into places more bulbous antibodies cannot, vanquishing a wider swath of viruses and bacteria. They look strikingly like monoclonal antibodies, and so have become darlings of pharma, particularly in cancer drug discovery.

A camels streamlined nanobodies arose from a mutation that removed the hinges that connect the Y-shaped arms of more conventional antibodies. Sometimes a mutation is a good thing!

Further infection protection comes from the milk protein lactoferrin, which fights hepatitis C.

Tolerating High Blood Sugar

A camel-herding people in India, the Raika, drink camel milk and dont get diabetes. Thats because camels tolerate high blood glucose levels, and some of that ability seeps into their milk.

P. Agrawal, at the SP Medical College, Bikaner, India and colleagues have conducted clinical trialsthat show that camel milk decreases blood glucose and hemoglobin A1c (a three-month-measure of blood glucose), and, in people with type 1 diabetes, reduces the insulin requirement by up to 30 percent .

How can camels have high blood sugar yet low HbA1C? In most animals, the beta chains of hemoglobin bind glucose at several points, upping HbA1C. This doesnt happen in camels. If glucose binding to hemoglobin in us is like Velcro, then in camels, its like contact between a boot and slippery ice.

Conserving Water

Milk requires water, and camels are masters at conserving it. A self-contained cooling system, as Christina describes it, cycles body water from a camels nostrils to its mouth. The multi-layered eyelids and double row of eyelashes keep out blowing sand. Their unique oval blood cells compress as camels safely dehydrate, then swell up again as they refill with water, keeping their blood flowing in extreme conditions.

Camels dont dry out in the desert, as we would, thanks to variants of the genes that encode the cytochrome P450 (CYP) enzymes. They enable camels to resorb lots of water while tolerating high salt conditions, without their blood pressure spiking. Their kidneys are keenly attuned to taking back water.

Camel milk is also high in the calming neurotransmitter GABA, low in lactose, and has more vitamin C than cows milk.

Beyond Milk

The astonishing adaptations of the camel arent restricted to its milk. Here are a few more that have their roots in the animals genes.

Variations on the Camel Theme

About 94% of the worlds 35 million camels are the domesticated, one-humped dromedaries (Camelus dromedaries) of northern and eastern Africa, the Arabian Peninsula, and southwest Asia. A feral branch lives in Australia. Wild dromedaries are extinct and are in a separate genus, Camelops hesternus. They dwelled in western North America.

About 2 million two-humped domesticated Bactrian (Camelus bactrianus) camels live on the steppes of central Asia, and each weighs about 1,000 pounds. Fewer than 100 wild Bactrian camels remain; they split from a shared ancestor about 700,000 years ago. Today they live in Mongolia and in northwest Chinas Xinjiang Province, in an area that was a nuclear testing site for 45 years. In 2008 the wild Bactrians were designated a distinct species, Camelus ferus.

When bactrian and dromedary camels interbreed, most offspring have one hump, some with a dip in the middle.

Camel Genomics

Camel genomes are remarkably diverse with many mutations, perhaps because people havent controlled their breeding. Doing so is challenging.

The jelly-like consistency of camel semen complicates both freezing and using artificial insemination. Still, researchers from Oman and France recently published a report about possible genetic improvements: selecting for traits that ease of using milking machines, provide resistance to infections, improve racing ability, and enhance beauty. Camels are, after all, gorgeous creatures.

The first camel genome sequence, published in 2012, revealed 20,821 genes splayed out among 37 chromosome pairs. Some 2,730 genes have evolved faster in camels than in their cattle relatives, many involved in carbohydrate and lipid metabolism. Perhaps the unusual variants contribute to the camels ability to conserve water.

Researchers from Kuwait University report in PLOS Onethat they analyzed DNA from the blood, spit, and hair of nine camels, concluding that tail hair follicle DNA is the best tissue source to create a biobank.The International Camel Consortium for Genetic Improvement and Conservation promotes camel genetic conservation.

Bring on the Camel Fro-Yo!

The milk isnt cheap. Camel Milk Cooplists $36.99 for a weeks supply. And as Christinas book explains, theres little to no incentive to conduct a clinical trial or to attempt to replicate natures magical mix of milk ingredients. Camel Crazy includes a users guide and directory of global sources.

The milk is available in liquid, frozen, and powdered form. Camel-milk-containing products include skin cream, cheeses, ice cream pops, chocolate milk, and a delectable-looking sweet called barfi, which means snow in Persian (not vomit).

When will camel milk come to Starbucks?

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Camel Milk and Autism: Connecting the Genetic Dots | DNA Science Blog - PLoS Blogs

Mutations in theMRAP2 gene may increase the risk for obesity, high blood sugar, and hypertension, a large genetic study has found.

The study, Loss-of-function mutations in MRAP2 are pathogenic in hyperphagic obesity with hyperglycemia and hypertension, was published in the journal Nature Medicine.

Loss-of-function mutations disrupt the function of the resulting protein. In the case of MRAP2, such mutations have been associated with obesity in mice. The same study found four rare variants in this gene among 976 people with severe obesity and none in the controls, but it did not analyze the function of the altered proteins.

The MRAP2 protein (melanocortin-2 receptor accessory protein 2) is known to increase the activity of another protein, called MC4R (melanocortin 4 receptor). Importantly, mutations in the MC4R gene have been found to constitute the most frequent single genetic cause of obesity.

Researchers in France conducted a large-scale sequencing of the protein-coding portions (exons) of MRAP2 in 9,418 people 7,239 adults and 2,179 children or adolescents to better understand how mutations in this gene impact protein function.

Results revealed 23 rare genetic variants, 14 of which had never been reported. These variants were associated with an increased risk of obesity, 3.8-fold in adults and 2.91 times in children/adolescents.

The team then performed in vitro experiments to assess protein function. Cells expressing any of six MRAP2 mutations had decreased MC4R signaling, suggesting a link between such variants and obesity.

Seven loss-of-function variants were identified in seven obese or overweight adults of European origin and in three obese European adolescents. Most (75%) people carrying these mutations had abnormal eating behavior, including overeating.

Also, most carriers had high blood sugar (hyperglycemia) and high blood pressure (hypertension). According to the scientists, this contrasts with mutations in other obesity-related genes (such as MCR4), as the frequency of hyperglycemia and hypertension is lower in people carrying those mutations.

The researchers then used beta cells, responsible for producing the hormone insulin in the pancreas, and found that lowering the levels of MRAP2 led to decreased insulin production in those cells.

These results suggest that MRAP2 mutations could have a direct functional deleterious [harmful] effect on beta cells, the researchers wrote.

They suggested that effects on the receptor of the hormone grehlin (key in appetite and growth hormone release) could link changes in MRAP2 to high blood pressure.

Overall, the study suggests that mutations in MRAP2 could lead to obesity and related health problems, but medications already in development may be helpful.

Because MRAP2 deficiency partly impacts the MC4R pathway, the eating behavior problems in people deficient in MRAP2 might be treated by the MC4R agonist setmelanotide, the investigators wrote.

Marisa holds an MS in Cellular and Molecular Pathology from the University of Pittsburgh, where she studied novel genetic drivers of ovarian cancer. She specializes in cancer biology, immunology, and genetics. Marisa began working with BioNews in 2018, and has written about science and health for SelfHacked and the Genetics Society of America. She also writes/composes musicals and coaches the University of Pittsburgh fencing club.

Total Posts: 9

Jos is a science news writer with a PhD in Neuroscience from Universidade of Porto, in Portugal. He has also studied Biochemistry at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario in London, Ontario, Canada. His work has ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimers disease.

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Obesity Risk Linked to Mutations in MRAP2 Gene, Study Says - Genetic Obesity News

Mila Makovec has high pigtails in her dark hair and a cloth doll tucked under her arm as she wakes up in a hospital bed, where shes just been injected with a one-of-a-kind drug intended to save her life.

The drug works for only one person in the world this 9-year-old girl from Boulder.

In a spectacular example of what the future might hold for precision medicine, the drug was made only for her in a quest to save Mila from a neurological disease that is destroying her brain. Her DNA is in the formula. The 22-letter genome sequence in the drugs recipe matches the one in Milas cells that is broken.

It is the first time the FDA has approved a drug for a single person.

The drug appropriately called milasen might not have come soon enough to save Mila, as it can only slow the process of degeneration, not replace the brain cells that have already died.

But this story is no longer just about Mila; it never actually was.

This is not just for my daughter anymore, said Julia Vitarello, who took to social media to fundraise and find a researcher and drug manufacturer who would help her. This is for something much bigger.

Milas case catapulted specialized drug development at least a decade into the future, her doctors say, opening a new path for other children with rare genetic diseases that have no cure.

Childrens Hospital Colorado, where Mila was diagnosed three years ago and now receives her treatment, and Boston Childrens, where her drug was designed, are leading the way in creating a model in which academic researchers could help perhaps a handful of children each year by crafting one-of-a-kind medicines. Next year, Childrens Colorado will begin whole-genome sequencing with a new machine called a Novaseq, a major step in the process of finding mutations in DNA.

The whole concept raises ethical questions for sure: How safe is it to initiate a clinical trial for a single child? Who makes sure the children who could benefit most not just those whose families have money or the ability to raise money get the specialized treatment?

Vitarello, who created Milas Miracle Foundation and raised $3 million while trying to save her daughter, wants to establish funding for children who need drugs tailored to their own cellular biology. She suggests an admissions process where the researchers deciding whether to help a child do not know that childs name, face or ability to pay.

There are going to be parents who are going to do anything for their kid, Vitarello said. They are going to come with money. Thats totally fine, no judgment. I would do the same thing. But in an ideal world, there would be patients coming through a funnel with no names or faces or money attached. Whoever is at the table makes the best decision.

The path forward is likely in the academic, nonprofit space, Vitraello said. She is initiating talks with the National Institutes of Health, the largest public funder of biomedical research, as well as research institutions, the FDA and the pharmaceutical industry. An estimated 1.3 million people with rare genetic diseases could potentially benefit from a treatment like Milas, she said.

There are 1.3 million kids that are dying that have no other treatment, no pharma company is going to help them, there is nothing that we can do, and now suddenly, weve opened up a pathway for that, she said Tuesday at the hospital in Aurora, as Mila rested following her injection. The only way to get it is to have more academic institutions treat more kids one, two, five, 10. Open it up.

The goal is that kids with flaws in their DNA could receive precision medicine sooner, halting neurological diseases before they steal the ability to walk, talk, eat or see.

Mila was a perfectly healthy child the first three years of her life. She was learning to ski, went hiking with her parents and had a vocabulary advanced beyond her years.

Her mom noticed the subtle changes before anyone the way she pulled books close to her face because she couldnt see, how her feet turned inward, that she began bumping into things and fell for no reason, how she stuttered sometimes but it wasnt like typical stuttering.

Vitarello brought her to 100 doctors and therapists from the East Coast to the West and in Canada, many of whom told her to calm down and that her daughter seemed fine. I had doctors tell me I was pretty much crazy. Very top level doctors told me to chill out, she said. Well, I wasnt going to chill out. I just kept going.

By age 7, Mila was having trouble walking and eating and was going blind. Her body was wracked with multiple seizures each day.

I spent three years trying to figure out what was wrong with her, Vitarello said. I basically gave up and brought her to the ER at Childrens Colorado.

Mila was admitted and her case assigned to Dr. Austin Larson, a geneticist whose main job at the hospital is to figure out whats wrong with patients who have an undiagnosed disease. An MRI found that the part of Milas brain that is responsible for balance, the cerebellum, was smaller than expected. But it was a genetic test that for the first time gave Vitarello a name for Milas illness: Batten disease, and a specific type of Batten that is so rare, just 25 people in the world are known to have it.

The disease occurs when both of a childs two CNL7 genes are mutated one mutation from each parent.

Larson was able to identify the defective gene from Milas father, but could not find one from her mother. At the time, Childrens Colorado along with most places didnt have the technology to search that deeply into Milas DNA through whole-genome sequencing, and Larson warned Milas family that it was likely impossible to find a clinical lab that could. She would need a researcher.

Vitarello turned to Facebook, begging for help for Mila but also so she could find out if her son, who was 2 at the time and completely healthy, had the same devastating disease that was taking away her daughter.

I was going to get nowhere with Mila unless I just opened up my story fully, to everyone, her mom said.

Dr. Larson had given her enough information and the right words to make a plea. A Boston physician saw her message and connected her with Dr. Timothy Yu, a neurogeneticist at Boston Childrens.

At the same time, the FDA had just approved a new drug called Spinraza, the first drug to treat a separate genetic condition called spinal muscular atrophy. The drug, injected into the fluid around the spinal cord, helped babies in clinical trials improve head control, sitting and standing.

The way Spinraza was designed was a game-changer for medicine and key in helping Mila. Yu and his team in Boston wondered if they could make a similar drug for the Colorado girl.

The Boston team spent days staring at screens of Milas DNA sequences until they discovered the other piece of the genetic puzzle in addition to the gene mutation from her father, Mila had inherited extra genetic material from her mother. The combination meant that, in the most basic terms, Mila had a sequence of broken DNA in her cells.

The drug created only for Mila contains little pieces of synthetic genetic material that search for a specific 22-letter sequence and cover it up so that her cells cannot read it. We are taking a Band-Aid and sticking it onto that part, said Dr. Scott Demarest, a pediatric neurologist at Childrens Colorado and a specialist in rare genetic epilepsies. That is literally what is happening. It is sticking to that spot so that the cell skips over that and goes to the next part that is correct.

The only difference between Spinraza and milasen is the genetic sequence inside the drugs send Band-Aids to different addresses.

After discovering the genetic flaw, Yu in Boston and Larson in Colorado called Milas mom together to give her the news. Her son did not have either of the recessive genes, and her daughter had both.

It was a huge mix of extreme happiness and, within the same second, just extreme falling-to-the-floor sadness for Mila, Vitarello recalled. My daughter had gotten both of the bad mutations and my son had gotten both of the good ones.

Next, Vitarello had to persuade a drugmaker to make a drug for one, and the FDA to allow doctors to inject it in her daughters spinal fluid.

The stars aligned, she says, still in disbelief.

Milas team made it happen by emphasizing that although this drug had the potential to work only on one person, the process could become a blueprint for other patients. Only the DNA sequence in the medicine would change.

They persuaded a drug manufacturer in California, TriLink Biotechnologies, to make Milas drug. And the FDA agreed to speed up the clinical trial process by allowing Yu to test the drug on rats at the same time Mila was receiving her first dose. The doctor had first tested it on Milas skin cells.

Milasen is technically now in clinical trial a trial of one patient involving two childrens hospitals.

The night before Milas first injection in January 2018, as Vitarello went for a run in subzero Boston, she told herself she was OK with whatever happened. Mila was out of time. Vitarello had seen the descriptions online and knew where Mila was headed.

My daughters trajectory of not treating her was so black and white, Vitarello said. Everyone always wonders what is going to happen to your life. When you have a rare disease, you can see exactly what is going to happen to your child ahead of time and its not a good thing.

I figured the worst-case scenario was not her dying, it was her being in pain, Vitarello said, recalling that she asked Yu to tell the FDA that she thought the drugs potential benefits outweighed the risk. I said, If my daughter dies on the spot, Im OK with that.

Instead, the injections that first year seemed to stop the diseases progression. Mila quit eating through a g-tube and started eating her moms pureed food again. She could hold up her head and her upper body, and her walking improved. Her seizures decreased from 30 a day to two or three.

Quality of life, those are huge, Vitarello said.

Now in the second year of treatment, some of Milas symptoms have declined, but not as steeply as other children with her disease. Milas team has upped her doses and started injecting them every two months instead of every three, but they have no precedent to follow.

They could find out years from now that they were giving Mila 1,000 times too little, her mother said.

I honestly dont know if it was in time for Mila, Vitarello said. She was really progressed when she received her treatment. There is still hope.

The key to saving more children from rare genetic diseases is diagnosing them earlier ideally at birth.

What if we found this three years sooner? Larson asked. I think about that a lot. What would it have taken to have found this the first time that (Vitarello) took Mila to a physician and said, I am concerned about the subtle difference in the way she walks?

The answer is it takes having a very broad test and being very good at interpreting that very broad swath of information.

Science is a ways off from being able to detect diseases as rare as Milas in newborns. But breakthroughs are coming for other genetic diseases.

Starting in January, spinal muscular atrophy will become one of 38 genetic diseases newborn babies are screened for via blood tests, said Raphe Schwartz, chief strategy officer for Childrens.

Childrens intends to take what it has learned through Milas case, partner with other institutions and use it to help more children, Schwartz said. What we learn reveals the roadmap for the future, he said. The future ones we do are more effective and less expensive over time.

There is a sense of urgency, but also caution.

We want to make sure we are doing it right, we are doing it safely, we are doing it for kids who are going to benefit the most, Demarest said. There are ethical challenges around it. We need to be very thoughtful and careful that we are doing this the right way, but were also doing it in a way that allows this to be a reality for kids as soon as possible and for as many as possible.

For now, Vitarello is grateful that Mila can receive her treatments in Colorado. Until September, they were traveling to Boston every other month for 10 days, but now they can leave home after breakfast on treatment days and return by dinner.

On Tuesday, Vitarello recited Goldilocks and the Three Bears and sang camp songs while Mila, bundled in blankets, received the 10-minute injection in her lower back, which Vitarello said doesnt seem to hurt Mila. They celebrated Milas 9th birthday last week, and her little brother, now 5, picked out a squishy toy and a sequined mermaid for her birthday presents.

Im faced with a huge amount of sadness around this, but at the same time, its making such a huge difference that it gives a lot of purpose to her life and it gives a lot of purpose to my life, Vitarello said. We are still fighting hard for Mila. But I can see this making a much bigger impact.

This reporting is made possible by our members. You can directly support independent watchdog journalism in Colorado for as little as $5 a month. Start here: coloradosun.com/join

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This miracle drug was designed and manufactured for just one person a 9-year-old Boulder girl - The Colorado Sun

Autoimmune diseases are immune system disorders where the bodys immune system attacks its own tissues. Examples of common autoimmune diseases include rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, type 1 diabetes, multiple sclerosis (MS) and others.

A peculiarity of autoimmune diseases is that they have many genes in common, but they develop differently. For example, why does a patient with an autoimmune disease become a type 1 diabetic rather than have rheumatoid arthritis?

Decio L. Eizirik, a researcher at Universit Libre de Bruxelles Centre for Diabetes Research in Belgium, who is also a senior research fellow at the Indiana Biosciences Research Institute, recently published research in the journal Nature Genetics that found significant insight into this question. Eizirik took time to speak with BioSpace about the research and how a researcher in Belgium came to collaborate with researchers in Indiana, Spain, the UK and the U.S. National Institutes of Health.

Several autoimmune diseases, such as type 1 diabetes, rheumatoid arthritis, multiple sclerosis, etc., have as much as 30 to 50% of their candidates genes in common, said Eizirik, raising the question on why in some individuals the immune system attacks, for instance, the insulin-producing beta cells, causing type 1 diabetes, while in others it targets joint tissues, leading to rheumatoid arthritis. Most of the research in the field has focused on the role for these candidate genes on the immune system, but our work indicated that many of these candidates genes affect the function and survival of pancreatic beta cells, leading to a misguided dialogue between them and the immune system that culminates in diabetes.

The early stages of type 1 diabetes, for example, show local autoimmune inflammation and progressive loss of the pancreatic beta cells that produce insulin. How these genetic transcription factors, or cytokines, interact with the beta-cell regulatory environment, and the changes that occur, suggest a key role in how the immune system gets triggered to attack the beta cells.

The research was conducted by Eizirik, Lorenzo Pasquali from the Institucio Catalana de Recerca I Estudis Avancats (ICREA) in Barcelona, Spain, and colleagues from Oxford, UK; Pisa, Italy, and the NIH. For about 20 years, Eizirik has run a diabetes-focused laboratory in Brussels. In August 2019, he launched a new laboratory at the IBRI, where, he said, three top scientists and assistants, Donalyn Scheuner, senior staff scientist at IBRI, Bill Carter, research analyst at IBRI, and Annie Rocio Pineros Alvarez, postdoctoral fellow in medicine at Indiana University, are already working. These two laboratories are working closely togetherfor instance, we have weekly meetings by videoconference, and besides my regular visits to the IBRI, scientists are moving between our European and USA labs on a temporary or permanent basis.

The IBIR was created by the State of Indiana and the states leading life science companies, academic research universities and medical school, as well as philanthropic organizations. The focus is on metabolic disease, including diabetes, cardiovascular disease obesity and poor nutrition. Its laboratories and offices are housed in about 20,000 square feet of space in Indian University School of Medicines Biotechnology Research and Training Center in Indianapolis. It expects to move into a new 68,000-square-feet site in mid-2020.

Eizirik said, The IBRI offers a unique opportunity to translate our basic research findings to the clinic, and we are working closely together with colleagues at Indiana University, particularly Carmella Evans-Molina, director of the Indiana Diabetes Research Center (IDRC) and the IDRC Islet and Physiology Core, to confirm our basic research findings in patients samples, and to eventually bring them to the clinic.

The specific research study looked at the binding of tissue-specific transcription factors. Transcription factors are basically proteins whose job it is to turn genes on or off by binding to DNA. So, for example, there are specific transcription factors whose job it is to regulate insulin production in pancreatic beta cells. In the case of this research, Eizirik and his team studied tissue-specific transcription factors that open the chromatin. Chromatin is a complex of DNA and protein found in the nucleus of the cell. It allows long DNA molecules to be packaged, typically in the form of chromosomes.

For gene transcription to occur, Eizirik said, chromatin must open and provide access to transcription factors. This allows binding of pro-inflammatory transcription factors induced in the beta cells by local inflammation.

For certain people who are genetically predisposed to type 1 diabetes, this leads to the generation of signals by the beta cells, Eizirik said, that contribute to attract and activate immune cells, rendering beta cells a potential target to the immune system.

Eizirik said, These observations have clarified the role for pancreatic beta cells in type 1 diabetes and provided an explanation for the reasons behind the immune system targeting beta cells.

The amplifying loop mechanism observed potentially explains other autoimmune diseases. Eizirik notes, Binding of tissue-specific transcription factors, within an inflammatory context and in genetically predisposed individuals, could generate signals that would attract and activate immune cells against specific target tissues.

Testing the theory in other autoimmune diseases will be required to verify it, but potentially could open up new therapies or preventive treatments for type 1 diabetes and other autoimmune diseases.

Type 1 diabetes has a strong genetic component, Eizirik said. At least 50% of the disease risk is due to genetic causesand understanding the role for candidate genes in the disease may point to novel therapies. For instance, up to now, nearly all therapeutic approaches to prevent type 1 diabetes have targeted the immune system, with little success. Our findings suggest that we must also take steps to directly boost beta cell survival.

He compared targeting the immune system only in type 1 diabetes to trying to fly a plane with only one wing. Our present and previous data suggest that we need two wings: first, to re-educate the immune system to stop its attack on the beta cells, and second, to increase the beta cell resistance to the immune attack, and to find means to restore the lost beta cell mass. Unfortunately, to achieve these goals in both type 1 diabetes and other autoimmune diseases is not easy, and we must redouble our efforts.

The next stages of the research will be to study the function of two novel candidate genes for type 1 diabetes that were discovered in the research. They both act at the beta cell level. He expects to conduct that research with Pasquali. The second stage is to evaluate the impact of other immune mediators that act earlier in the disease course at the beta cell level. And the third stage is to test their hypothesis regarding the role for the target tissue in other autoimmune diseases.

In addition to that ambitious agenda, Eizirik and his group are establishing an Inducible Pluripotential Cell Core at the IBRI.

Eizirik said, This will allow us to de-differentiate, for instance, skin cells from patients into pluripotential cells, and then to differentiate them into pancreatic beta cells. This will allow us to study the impact of the novel candidate genes we are discovering on beta cell function and survival, again in collaboration with Lorenzo Pasquali and Carmella Evans-Molina. This will also provide an excellent model to test new drugs to protect the beta cells in early type 1 diabetes.

Original post:
Researchers Working to Understand Why Some Patients with Autoimmune Diseases Develop Diabetes Instead of Arthritis - BioSpace

DUBLIN--(BUSINESS WIRE)--The "Global Cancer Biomarkers Market Analysis 2019" report has been added to ResearchAndMarkets.com's offering.

The Global Cancer Biomarkers market is expected to reach $37.99 billion by 2026 growing at a CAGR of 14.2% from 2018 to 2026.

Factors such as rise in technological advancements and increase in Incidence of Cancer diseases are driving the market growth. Though, high capital investment and technical issues related to sample collection and storage are projected to inhibit the growth of the market. Moreover, emerging economies and personalized medicine may provide ample opportunities for the market growth.

By biomarker type, protein biomarkers segment acquired significant growth in the market is mainly attributed to the tremendous capability of protein biomarkers in cancer detection, diagnostics, prognostics, and clinical & therapeutic applications; and minimal cost of the protein biomarker tests as contrasted with genetic biomarker tests. The rising focus of pharmaceutical organizations towards the discovery of protein biomarkers is additionally expected to fuel the development of this market during the forecast period.

The key vendors mentioned are Qiagen N.V., Thermo Fisher Scientific, GE Healthcare, Roche Diagnostics, Abbott Laboratories, Illumina, Danaher Corporation, Agilent Technologies, Sysmex Corporation, Merck & Co., Quest Diagnostics, Becton, Dickinson and Company, Hologic, Myriad Genetics, Bio-Rad Laboratories and Biomrieux S.A.

Key Questions Answered in this Report

Key Topics Covered

1 Market Synopsis

2 Research Outline

2.1 Research Snapshot

2.2 Research Methodology

2.3 Research Sources

2.3.1 Primary Research Sources

2.3.2 Secondary Research Sources

3 Market Dynamics

3.1 Drivers

3.2 Restraints

4 Market Environment

4.1 Bargaining power of suppliers

4.2 Bargaining power of buyers

4.3 Threat of substitutes

4.4 Threat of new entrants

4.5 Competitive rivalry

5 Global Cancer Biomarkers Market, By Category

5.1 Introduction

5.2 Cancer Biomakers of Disease

5.3 Cancer Biomakers of Exposure

6 Global Cancer Biomarkers Market, By Method

6.1 Introduction

6.2 Assay Development

6.3 Biomarkers and Testing

6.4 Sample Preparation

7 Global Cancer Biomarkers Market, By Biomarker Type

7.1 Introduction

7.2 Cancer Antigen 15-3 (CA 15-3)

7.3 Cancer Antigen 27-29 (CA27-29)

7.4 Carbohydrate Antigen 19-9 (CA 19-9)

7.5 Carcinoembryonic antigen (CEA)

7.6 Epigenetic Biomarkers

7.7 Genetic Biomarkers

7.8 Glass Transition Temperature (Tg)

7.9 Glyco-biomarkers

7.10 Glycomic Biomakers

7.11 Glycoprotein Biomarkers

7.12 Human Chorionic Gonadotropin (Hcg)

7.13 Human Epidermal Growth Factor Receptor 2 (HER2)

7.14 Human Epididymis Protein 4 (HE4)

7.15 Metabolic Biomakers

7.16 Microsatellite Instability (MSI) / Measles, Mumps and Rubella (MMR)

7.17 Protein Biomarkers

7.18 Proteomic Biomarkers

7.19 Risk of Ovarian Malignancy Algorithm (ROMA)

7.20 Tumor Mutational Burden (TMB)

7.21 Tumor-Infiltrating Lymphocytes (TILs)

8 Global Cancer Biomarkers Market, By Cancer Type

8.1 Introduction

8.2 Bladder Cancer

8.3 Blood Cancer

8.4 Breast Cancer

8.5 Cervical Cancer

8.6 Colorectal Cancer (CRC)

8.7 Kidney Cancer

8.8 Leukemia

8.9 Liver Cancer

8.10 Lung Cancer

8.11 Melanoma

8.12 Non-Hodgkin's Lymphoma

8.13 Ovarian Cancer

8.14 Prostate Cancer

8.15 Stomach Cancer

8.16 Thyroid Cancer

9 Global Cancer Biomarkers Market, By Technology

9.1 Introduction

9.2 Bioinformatics

9.3 Cytogenetics-based Tests

9.4 Imaging Technologies

9.5 Immunoassays

9.6 IVD Multivariate Index Assays

9.7 Omic technologies

10 Global Cancer Biomarkers Market, By Test Type

10.1 Introduction

10.2 Alpha-Fetoprotein (AFP) Tests

10.3 Anaplastic Lymphoma Receptor Tyrosine Kinase Gene (ALK) Tests

10.4 BReast CAncer gene (BRCA) Tests

10.5 Cancer Antigen (CA) Tests

10.6 Carcinoembryonic Antigen (CEA) Tests

10.7 Circulating Tumor Cell (CTC) Tests

10.8 Companion Diagnostic Tests (CDx)

10.9 Estimated Glomerular Filtration Rate (EGFR) Mutation Tests

10.10 Human Epidermal Growth Factor Receptor 2 (HER2) Tests

10.11 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) Mutation Tests

10.12 Laboratory Developed Tests (LDTs)

10.13 Prostate-specific Antigen (PSA) Tests

11 Global Cancer Biomarkers Market, By Analytical Technique

11.1 Introduction

11.2 Immunohistochemistry (IHC)

11.3 Next Generation Sequencing (NGS)

11.4 Polymerase Chain Reaction (PCR)

12 Global Cancer Biomarkers Market, By Product

12.1 Introduction

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Global Cancer Biomarkers Market, Forecast to 2026 - Emerging Economies & Personalized Medicine to Provide Ample Industry Opportunities -...