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Taysha Gene Therapies Receives Rare Pediatric Disease Designation and Orphan Drug Designation for TSHA-102 as a Treatment for Rett Syndrome

Program leverages novel miRARE platform technology used to control transgene expression on a cellular basis

TSHA-102 anticipated to submit Investigational New Drug application in 2021

Taysha Gene Therapies Inc. (Nasdaq: TSHA), a patient-centric gene therapy company focused on developing and commercializing AAV-based gene therapies for the treatment of monogenic diseases of the central nervous system in both rare and large patient populations, today announced that it has received rare pediatric disease designation and orphan drug designation from the U.S. Food and Drug Administration (FDA) for TSHA-102, an AAV9-based gene therapy in development for the treatment of Rett syndrome. Taysha anticipates that it will submit an Investigational New Drug (IND) application for TSHA-102 to the FDA in 2021.

Rett syndrome is one of the most common genetic causes of severe intellectual disability worldwide, with a prevalence of over 25,000 cases in the U.S. and European Union (EU). It is an X-linked disease that primarily occurs in females, but it can be seen very rarely in males. It is usually recognized in children between six to 18 months of age as they begin to miss developmental milestones or lose abilities they had developed. Individuals with Rett syndrome also show symptoms that include loss of speech, loss of purposeful use of hands, loss of mobility, seizures, cardiac impairments, breathing issues and sleep disturbances.

“Patients with Rett syndrome are currently managed with symptomatic treatments as there are no therapies approved to treat the underlying cause of disease,” said Berge Minassian, M.D., Chief Medical Advisor of Taysha and Chief of Pediatric Neurology at the University of Texas Southwestern Medical Center (UT Southwestern). Dr. Minassian is credited with describing the CNS isoform of the MECP2 gene which is responsible for neuronal and synaptic function throughout the brain. “Gene therapy offers a potentially curative option for patients suffering with Rett syndrome.”

Rett syndrome is caused by mutations in the MECP2 gene. TSHA-102 is designed to deliver a healthy version of the MECP2 gene as well as the miRNA-Responsive Auto-Regulatory Element, miRARE, platform technology to control the level of MECP2 expression. “TSHA-102 represents an important step forward in the field of gene therapy, where we are leveraging a novel regulatory platform called miRARE to prevent the overexpression of MECP2,” said Steven Gray, Ph.D., Chief Scientific Advisor of Taysha and Associate Professor in the Department of Pediatrics at UT Southwestern. “In collaboration with Sarah Sinnett, Ph.D. to develop miRARE, our goal was to design a regulated construct that allowed us to control MECP2 expression to potentially avoid adverse events that are typically seen with unregulated gene therapies.”

The FDA defines a rare pediatric disease as a serious or life-threatening disease in which the disease manifestations primarily affect individuals aged from birth to 18 years. Pediatric diseases recognized as “rare” affect under 200,000 people in the U.S. The Rare Pediatric Disease Priority Review Voucher Program is intended to address the challenges that drug companies face when developing treatments for these unique patient populations. Under this program, companies are

11-year-old with rare cancer blogs to show good and bad sides of disease

When Nevaeh Williams was just 8, she was diagnosed with an extremely rare cancer. Doctors were unsure if she’d ever be cancer-free, but the treatment worked and she enjoyed two years playing softball, enjoying math class with friends and just being a kid. This August, a scan revealed the cancer had returned and her mom, Alana Simmons-Williams, was distraught.

“I’ve always had a little bit of anxiety when it would be time for scans but the anxiety was starting to ease,” Simmons-Williams, 34, who lives outside of Savannah, Georgia, told TODAY. “At her two-year scan (the doctor) told me the cancer came back. I was devastated, like heartbroken. I want to say it was worse than hearing it the first time.”

For two years, Nevaeh enjoyed life like any other child her age. But at recent scans, she and her family learned her rare cancer had returned. (Courtesy Nevaeh's Victory Against Cancer)
For two years, Nevaeh enjoyed life like any other child her age. But at recent scans, she and her family learned her rare cancer had returned. (Courtesy Nevaeh’s Victory Against Cancer)

But Nevaeh, now 11, had a different reaction.

“For her going through it a second time, she’s like, ‘OK, the first time they told me I wasn’t going to be able to be cancer-free at all and I did it. I beat it,’” Simmons-Williams said. “She wanted to blog her journey … She was like, “I want to record it this time. I want to show everyone what it’s like.’”

A shocking diagnosis

One day when Nevaeh was 8, she was doing a cartwheel when Simmons-Williams noticed her daughter’s stomach was bloated. Simmons-Williams asked her daughter if she felt sick or was constipated, but Nevaeh felt fine. They visited their pediatrician who recommended they go to the emergency room.

At first doctors believed Nevaeh had Ewing sarcoma, a cancer that affects the bones. But Simmons-Williams didn’t think that’s what Nevaeh had and pushed for another opinion.

“She didn’t have any problems with her bones. She just had a tumor in her stomach and tumors throughout her chest wall,” she said. “That’s when it was revealed that it was desmoplastic small round cell tumors.”

Desmoplastic small round cell tumors are so rare that there are only 200 known cases of it since 1989, according to the National Cancer Institute Center for Cancer Research.

“There is no standard treatment plan for DSRCT,” Simmons-Williams explained. “They commonly use the treatment plan that they use for Ewing sarcoma.”

Nevaeh, 11, gives her social media followers an unfiltered look about what having cancer is like. She finds strength in the support she receives. And, they learn more about cancer. (Courtesy Nevaeh's Victory Against Cancer)
Nevaeh, 11, gives her social media followers an unfiltered look about what having cancer is like. She finds strength in the support she receives. And, they learn more about cancer. (Courtesy Nevaeh’s Victory Against Cancer)

They removed the mass in Nevaeh’s stomach, which was three pounds, and she also underwent hyperthermic intraperitoneal (HIPEC) treatment where doctors fill the abdomen with warm chemotherapy drugs to “wash” it. While she remained cancer-free for two years, doctors spotted a recurrence during her most recent scans and she began treatment in August.

“She doesn’t give up that easy,” Simmons-Williams said. “She has positive vibes.”

Vlogging through cancer

Before the cancer returned, Nevaeh’s hair had started growing

Social media helps mom spot rare cancer in her baby’s eye

A mom who followed her instincts is the reason her daughter is now being treated for cancer in her eye.

It was July 30, Jasmine Martin told “Good Morning America,” when she saw it. Prior to that day, she said, there had been “a small glow” in her daughter Sariyah’s eye. “But that day, it was like a moon.”

MORE: My son died from open-air carbon monoxide poisoning: Here’s what parents need to know

She posted the photo to Facebook looking for advice. Several people commented it could be cancerous.

Martin took her daughter to the pediatrician, who told the Knoxville, Tennessee, mom it was nothing to worry about. But Martin’s instincts told her otherwise.

“It was going to take weeks to get an ophthalmologist appointment,” Martin told “GMA.” So, she said she emailed the photo to a friend who worked at a hospital, who in turn showed it to a doctor.

MORE:A grandpa’s note, a bucket of baseballs and an emotional tweet

“She was taken to St. Jude’s that night,” Martin told “GMA.”

Since then, little Sariyah has been diagnosed with bilateral retinoblastoma. Retinoblastoma is, according to the St. Jude’s web site, a rare form of cancer affecting about 250-300 children each year. It “typically develops in children before 5 years of age. This cancer develops in the retina — the part of the eye that helps a person see color and light. Retinoblastoma may affect one or both eyes. In about two-thirds of all cases only one eye is affected,” the website reads.

There’s been strides forward and steps back for the 17-month-old and her family. Though the toddler was released from the hospital and sent home in late September, there’s cause for concern: a tiny spot in her left eye that had been laser treated has returned. At the same time, the tumor in her right eye, the one with the large glow, is shrinking.

Martin wrote in her most recent Instagram update, “We are so early in this but … days are mentally draining, because you just never know what they are going to find. It’s hard and it’s scary. If I allow myself to really think about it, if something happens to the good eye, then there’s still so many risks with the right eye. It’s a never ending battle of what ifs right now.”

Sariyah is “so happy,” her mom said, “You wouldn’t even know she is going through this,” she said, referring to hospital stays and chemotherapy. “Even when it makes her sick and she has a fever she’s still playing with her siblings,” Martin told “GMA.”

Friends and neighbors have stepped up to help the family through this difficult time, something Martin said has touched her. From meal trains to a car, “there are so many good people in the world,” she told “GMA.”

She’s hopeful sharing her Sariyah’s story, which she does both on Instagram and Facebook. will encourage mothers to follow their instincts when it comes to their

Another L.A. County child diagnosed with rare COVID-related syndrome

LOS ANGELES, CA - MARCH 04 , 2020 - L.A. County Department of Public Health Director Barbara Ferrer addresses a press conference held at the steps of Kenneth Hahn Hall of Administration to declare a health emergency as the number of coronavirus cases increased to seven, with six new cases in Los Angeles County. None of the new cases are connected to "community spread," officials said. All individuals were exposed to COVID-19 through close contacts. The additional cases were confirmed Tuesday night. Officials said three of the new cases were travelers who had visited northern Italy, two were family members who had close contact with someone outside of the county who was infected, and one had a job that put them in contact with travelers. One person has been hospitalized, and the others are isolated at home. (Irfan Khan / Los Angeles Times)
Barbara Ferrer, L.A. County Department of Public Health director, speaks at a news conference earlier this year. (Irfan Khan/Irfan Khan/Irfan Khan/Los Angeles Times)

Another Los Angeles County child has been diagnosed with a rare, potentially deadly syndrome believed to be related to the coronavirus, according to the county Health Department, bringing the total number of children with the ailment in the region to 41.

The Los Angeles County Department of Public Health said all of the children in the county diagnosed with multisystem inflammatory syndrome since the beginning of the pandemic had been hospitalized. The department said in a written statement Friday that 70% of the children with MIS-C were Latino, reflecting the high incidence of COVID-19 among Latinos overall.

Although none of the children reported to have the condition in Los Angeles County have died, nearly half have been sick enough to be admitted to the intensive care unit.

Children with the syndrome may have a fever and other symptoms including stomach pain, vomiting, diarrhea, rash, bloodshot eyes and exhaustion. The syndrome can cause different parts of the body to become inflamed, according to the Centers for Disease Control and Prevention.

“MIS-C is a new syndrome, and many questions remain about why some children and adolescents develop it after a COVID-19 illness or contact with someone with COVID-19 while others do not,” the CDC says.

As of Oct. 1, the CDC has reported 1,027 cases of multisystem inflammatory syndrome in children; 20 of the children with the ailment have died. Cases have been confirmed in 44 states and Washington, D.C.

Arizona, California, New York, New Jersey, Florida and Georgia are among the 10 states reporting the highest number of cases.

Just days before the Los Angeles County Department of Public Health announced the county’s 41st MIS-C case, federal health officials reported that multisystem inflammatory syndrome began to show up in adults in the United States and the United Kingdom in June.

Friday’s “Morbidity and Mortality Weekly Report” from the federal agency cited 27 adult cases and acknowledged that the data were limited. The CDC called it “an emerging syndrome” in adults and said more research was needed.

Like the childhood version of the ailment, MIS-A seems to affect Latinos and Blacks more than other populations. And, while it can kill, it usually does not.

“All but one of the patients with MIS-A described in this report belonged to racial or ethnic minority groups,” the CDC reported. “The majority (24 of 27) of patients with MIS-A survived, similar to those with MIS-C, associated with receiving care in acute, often intensive, health care settings.”

This story originally appeared in Los Angeles Times.

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People With This Rare Gene Mutation Can’t Smell Fishy Scents

KEY POINTS

  • Researchers conducted a smell test on over 9,000 participants 
  • Some of them couldn’t detect the fish scent or had a less intense experience 
  • Researchers found for these people the fish’s off-putting odor might smell even like caramel

A new study has revealed a genetic mutation that makes people who carry it be less susceptible to the smell of fish. For some of these people, fish’s off-putting odor might even smell like caramel or roses. 

Humans perceive smells using olfactory receptors, but of the 855 olfactory genes, about half are actually not functional. The reasons for this and why people have a “highly personalized” sense of smell remain a mystery.

To shed light on the matter, the researchers of a new study conducted a smell test wherein they presented 9,122 participants in Iceland with various smells including fish, cinnamon and liquorice, then asking them to name it and rate the pleasantness and intensity.

Overall, fish scent was rated as the least pleasant, but a small number of the participants had a somewhat different perception of the fishy smell.

The researchers found people with a mutation in a receptor gene called trace anime-associated receptor 5 (TAAR5) perceived the fish odor with trimethylamine (TMA) as a main ingredient as less intense. For instance, when presented with the smell of fish, those with the variant described it as having the smell of “caramel” or “rose” instead of other fishy odors such as “fermented skate” or “shark.” Some could not even recognize the scent at all.

On the other hand, those with an intact version of TAAR5 easily recognized the fishy scent.

“Carriers of the variant find the fish odor less intense, less unpleasant, and are less likely to name it accurately,” study first author Rosa Gisladottir of deCODE Genetics in Iceland said in a Cell Press news release.

Exactly how this variant affects the odor perception of people with the mutation is still unclear. 

TMA is also found in animal odors and human body secretions such as urine, blood and sweat.

Fish Pictured: Representative image of a crate of fish at a market. Photo: Pixabay

Additionally, the researchers also identified other variants that affected people’s ability to perceive the scent of liquorice and cinnamon. In this case, the participants found the scents to be more intense but also more pleasant.

These particular variants are distributed differently across the globe — 57% in East Asia and 11% in Europe.

“Spices containing trans-anethole, the main ingredient in the licorice odor, are widely used in Asian cuisine and traditional medicine,” the researchers wrote. “It could be speculated that variants associated with the perception of trans-anethole licorice odor conferred some advantage in East Asia, leading to the large frequency differences between populations.”

The study showed that even if humans do have reduced olfactory genes, the differences in variants make the sense of smell quite diverse.

“Altogether, our results provide a unique window into the effects of sequence diversity on human olfaction,” the researchers wrote. “An individual’s personalized

Saint Francis Service Dog in training receives rare root canal

ROANOKE, Va. – A Southwest Virginia dentist operated on a very unusual patient on Friday.

Walker the labrador retriever received a root canal in preparation for his work as a Saint Francis Service Dog.

The procedure is rare, but Saint Francis Service Dogs executive director Caball Youell said it was essential to Walker’s future career.

“His tooth was starting to cause him problems,” Youell said. “He needs to be able to pick things up comfortably, carry things for someone, or retrieve items.”

Walker got his canine tooth repaired at the Roanoke Animal Hospital, but none of the veterinarians there had the capacity to treat a root canal.

“We needed some special equipment and materials to do the root canal, and the dental community stepped up,” said Dr. Mark Finkler of Roanoke Animal Hospital.

Instead, Dr. Grant Throckmorton of Wythe Family Dentistry drove an hour from Wytheville to operate on Walker in Roanoke.

“The tooth is about twice as long as you’ll ever see a human tooth,” Throckmorton said. “They’re just massive. Some of my instruments don’t even work on dog teeth.”

The procedure went well, and Throckmorton finished the job in about an hour.

Youell said she is in the process of finding Walker’s permanent home, and she’s relieved his tooth will no longer cause him trouble.

“He’s going to want to go pick things up and bring them to you,” Youell said. “Whenever you see Walker, he looks around and says, ‘what present can I bring you?’”

Copyright 2020 by WSLS 10 – All rights reserved.

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Penn Medicine researchers discover a rare genetic form of dementia

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IMAGE: Abnormal neurofibrillary tangles (NFTs) — a buildup of tau protein in parts of the brain — helped Edward Lee, MD, PhD, an assistant professor of Pathology and Laboratory Medicine, and…
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Credit: Edward Lee

PHILADELPHIA — A new, rare genetic form of dementia has been discovered by a team of Penn Medicine researchers. This discovery also sheds light on a new pathway that leads to protein build up in the brain — which causes this newly discovered disease, as well as related neurodegenerative diseases like Alzheimer’s Disease — that could be targeted for new therapies. The study was published today in Science.

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by a buildup of proteins, called tau proteins, in certain parts of the brain. Following an examination of human brain tissue samples from a deceased donor with an unknown neurodegenerative disease, researchers discovered a novel mutation in the Valosin-containing protein (VCP) gene in the brain, a buildup of tau proteins in areas that were degenerating, and neurons with empty holes in them, called vacuoles. The team named the newly discovered disease Vacuolar Tauopathy (VT)–a neurodegenerative disease now characterized by the accumulation of neuronal vacuoles and tau protein aggregates.

“Within a cell, you have proteins coming together, and you need a process to also be able to pull them apart, because otherwise everything kind of gets gummed up and doesn’t work. VCP is often involved in those cases where it finds proteins in an aggregate and pulls them apart,” Edward Lee, MD, PhD, an assistant professor of Pathology and Laboratory Medicine in the Perelman School of Medicine at the University of Pennsylvania. “We think that the mutation impairs the proteins’ normal ability to break aggregates apart.”

The researchers noted that the tau protein they observed building up looked very similar to the tau protein aggregates seen in Alzheimer’s disease. With these similarities, they aimed to uncover how this VCP mutation is causing this new disease — to aid in finding treatments for this disease and others. Rare genetic causes of diseases can very often offer insight into more prevalent ones.

The researchers first examined the proteins themselves, in addition to studying cells and an animal model, and found that the tau protein buildup is, in fact, due to the VCP mutation.

“What we found in this study is a pattern we’ve never seen before, together with a mutation that’s never been described before,” Lee said. “Given that this mutation inhibits VCP activity, that suggest the converse might be true — that if you’re able to boost VCP activity, that could help break up the protein aggregates. And if that’s true, we may be able to break up tau aggregates not only for this extremely rare disease, but for Alzheimer’s disease and other diseases associated with tau protein aggregation.”

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Lee led this work with first author, Nabil Darwich, MD/PhD student in the Neuroscience Graduate Group at Penn.

These findings describe a new biologic function of VCP, define a

Report documents ‘very rare’ brain fluid leak linked to COVID-19 screening

Oct. 1 (UPI) — Researchers on Thursday described a “very rare” health complication linked with COVID-19 testing: brain fluid leak.

They documented what may be the first case — in a woman in her 40s — in a letter published by JAMA Otolaryngology-Head & Neck Surgery.

Those who have had sinus or skull-base surgery and those with known deformities of the skull base may be at risk for cerebrospinal fluid leak and should notify test takers of their history before getting screened for COVID-19, the researchers said.

“The good news is that this is a very rare event,” report co-author Dr. Jarrett E. Walsh, an ear, nose and throat specialist with the University of Iowa Hospitals and Clinics, told UPI.

“From a patient standpoint, there may be some discomfort with nasal swabs, but you should not have symptoms of persistent clear nasal drainage or significant bleeding after a swab,” particularly if physicians and healthcare workers follow the U.S. Centers for Disease Control and Prevention guidelines for sample collection, he said.

During COVID-19 screening, test-takers stick a 6-inch-long swab — what looks like a long Q-Tip — up each nostril, stopping in the cavity between the nose and mouth.

Although people who have had the test complain of some discomfort, rumors that it causes brain damage that were circulating on social media over the summer were unfounded.

Cerebrospinal fluid, or CSF, is the clear fluid found in the brain and spinal cord that serves as a cushion and provides protection to the brain inside the skull.

Physical trauma to the brain or spine can cause leaks. If a patient loses large amounts of the fluid, that can lead to severe complications, including brain infection, paralysis and coma, according to the Spinal CSF Leak Foundation.

Symptoms of such a leak include headaches, neck stiffness and light sensitivity.

In the case reported by Walsh and his colleagues, the woman reported these symptoms, as well as a metallic taste in her mouth and severe runny nose, after undergoing COVID-19 screening.

She had a history of intracranial hypertension — elevated CSF pressure in the brain — and had undergone surgery to remove nasal polyps more than 20 years earlier.

MRI and CT scans confirmed that she had CSF leak and identified a pre-existing skull-base defect. The skull base is essentially the “floor” beneath the brain.

She was admitted to the hospital and underwent surgery to repair the leak and skull-base defect and has since recovered.

“I would certainly not want to discourage anyone from [COVID-19] testing, but it should be done correctly, according to the CDC protocols,” Walsh said.

“Those who have had prior skull base surgery, extensive sinus surgery or [are at risk] for spontaneous CSF leaks, like intracranial hypertension, should alert testers or consider alternative testing types if available.”