Promising gene therapy delivers treatment directly to brain

Promising gene therapy delivers treatment directly to brain

Scientists say delivering gene therapy directly to the brain holds great promise

promising gene therapy delivers treatment directly to brain

When Rylae-Ann Poulin was a year old, she didn’t crawl or babble like other kids her age. A rare genetic disorder kept her from even lifting her head. Her parents took turns holding her upright at night just so she could breathe comfortably and sleep.

Then, months later, doctors delivered gene therapy directly to her brain.

Now the 4-year-old is walking, running, swimming, reading and riding horses — “just doing so many amazing things that doctors once said were impossible,” said her mother, Judy Wei.

Rylae-Ann, who lives with her family in Bangkok, was among the first to benefit from a new way of delivering gene therapy — attacking diseases inside the brain — that experts believe holds great promise for treating a host of brain disorders.

Her treatment recently became the first brain-delivered gene therapy after its approval in Europe and the United Kingdom for AADC deficiency, a disorder that interferes with the way cells in the nervous system communicate. New Jersey drugmaker PTC Therapeutics plans to seek U.S. approval this year.

Meanwhile, about 30 U.S. studies testing gene therapy to the brain for various disorders are ongoing, according to the National Institutes of Health. One, led by Dr. Krystof Bankiewicz at Ohio State University, also targets AADC deficiency. Others test treatments for disorders such as Alzheimer’s, Parkinson’s and Huntington’s.

Challenges remain, especially with diseases caused by more than a single gene. But scientists say the evidence supporting this approach is mounting — opening a new frontier in the fight against disorders afflicting our most complex and mysterious organ.

“There’s a lot of exciting times ahead of us,” said Bankiewicz, a neurosurgeon. “We’re seeing some breakthroughs.”

___

The most dramatic of those breakthroughs involve Rylae-Ann’s disease, which is caused by mutations in a gene needed for an enzyme that helps make neurotransmitters like dopamine and serotonin, the body’s chemical messengers. The one-time treatment delivers a working version of the gene.

At around 3 months old, Rylae-Ann began having spells her parents thought were seizures — her eyes would roll back and her muscles would tense. Fluid sometimes got into her lungs after feedings, sending her to the emergency room. Doctors thought she might have epilepsy or cerebral palsy.

Though they were nervous about the prospect of brain surgery, they realized she likely wouldn’t live past 4 years old without it.

Rylae-Ann had the treatment at 18 months old on November 13, 2019 — which her parents have dubbed her “reborn day.” Doctors delivered it during minimally invasive surgery, with a thin tube through a hole in the skull. A harmless virus carried in a functioning version of the gene.

“It gets put into the brain cells and then the brain cells make the (neurotransmitter) dopamine,” said Stuart Peltz, CEO of PTC Therapeutics.

Company officials said all patients in their clinical trials showed motor and cognitive improvements. Some of them, Peltz said, could eventually stand and walk, and continue getting better over time.

Bankiewicz said all 40 or so patients in his team’s NIH-funded study also saw significant improvements. His surgical approach is more involved and delivers the treatment to a different part of the brain. It targets relevant circuits in the brain, Bankiewicz said, like planting seeds that cause ivy to sprout and spread.

“It’s really amazing work,” said Jill Morris, a program director with the National Institute of Neurological Disorders and Stroke, which helped pay for the research. “And he has seen a lot of consistency between patients.”

One is 8-year-old Rian Rodriguez-Pena, who lives with her family near Toronto. Rian got gene therapy in 2019, shortly before her 5th birthday. Two months later, she held her head up for the first time. She soon started using her hands and reaching for hugs. Seven months after surgery, she sat up on her own.

“When the world was crumbling around us with COVID, we were at our house celebrating like it was the biggest party of our lives because Rian was just crushing so many milestones that were impossible for so long,” said her mom, Shillann Rodriguez-Pena. “It’s a completely different life now.”

___

Scientists say there are challenges to overcome before this approach becomes widespread for more common brain diseases.

For example, the timing of treatment is an issue. Generally, earlier in life is better because diseases can cause a cascade of problems over the years. Also, disorders with more complex causes — like Alzheimer's — are tougher to treat with gene therapy.

“When you’re correcting one gene, you know exactly where the target is,” said Morris.

Ryan Gilbert, a biomedical engineer at New York's Rensselaer Polytechnic Institute, said there can also be issues with the gene-carrying virus, which can potentially insert genetic information in an indiscriminate way. Gilbert and other researchers are working on other delivery methods, such as messenger RNA – the technology used in many COVID-19 vaccines – to deliver a genetic payload to the nucleus of cells.

Scientists are also exploring ways to deliver gene therapy to the brain without the dangers of brain surgery. But that requires getting around the blood-brain barrier, an inherent roadblock designed to keep viruses and other germs that may be circulating in the bloodstream out of the brain.

A more practical hurdle is cost. The price of gene therapies, borne mostly by insurers and governments, can run into the millions. The one-time PTC therapy, called Upstaza, costs more than $3 million in Europe, for example.

But drugmakers say they are committed to ensuring people get the treatments they need. And researchers are confident they can overcome the remaining scientific obstacles to this approach.

“So I would say gene therapy can be leveraged for many sorts of brain diseases and disorders,” Gilbert said. “In the future, you’re going to see more technology doing these kinds of things.”

The families of Rylae-Ann and Rian said they hope other families dealing with devastating genetic diseases will someday get to see the transformations they’ve seen. Both girls are continuing to improve. Rian is playing, eating all sorts of foods, learning to walk and working on language. Rylae-Ann is in preschool, has started a ballet class, and is reading at a kindergarten level.

When her dad picks her up, “she runs to me … just gives me a hug and says, ‘I love you, Daddy.’ he said. “It’s like it’s a normal day, and that’s all we ever wanted as parents.”

___

The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute’s Science and Educational Media Group. The AP is solely responsible for all content.

News Related

OTHER NEWS

These Are All The Dark Secrets The Duggars Don't Want You To Know About

GettyImages-138689214 The Duggars have been in the spotlight since 2008. They started off with their show on TLC 17 Kids and Counting from 2008-2009, followed by 18 Kids and Counting, ... Read more »

‘Soupocalypse’ taking over Seattle’s Fremont neighborhood

Soupocalypse is taking over the Fremont neighborhood starting Thursday! It’s your chance to “soup hop” for a good cause. The unique concept came to life in 2021 by Mischief on ... Read more »

Multiple drugs found in home, suspect wanted

Multiple drugs found in home, suspect wanted ARCHBALD, LACKAWANNA COUNTY (WBRE/WYOU) – State police are searching for a woman they say is a suspected drug dealer of meth and heroin ... Read more »

‘I feel like a failure’: Former police union head breaks down on stand in defamation trial

The former president of the State of Hawaii Organization of Police Officers is suing former Honolulu Police Department Chief Susan Ballard and the city for defamation. HONOLULU (HawaiiNewsNow) – The ... Read more »

Florida man wins $1M on scratch-off ticket after being cut in line at Publix

Stephen Espinoza, 43, took the lump sum payment of $820,000 from his million-dollar ticket Read more »

Disney divide: How Disney World caters to big spenders while working families pay the price

A new 'guide' says springing for the VIP treatment is the only way to enjoy Disney World Read more »

Tesla, Intel, Pfizer, Visa, Northrop Grumman: Why These 5 Stocks Are Drawing Investors' Attention Today

Tesla, Intel, Pfizer, Visa, Northrop Grumman: Why These 5 Stocks Are Drawing Investors’ Attention Today U.S. markets surged on Thursday, following the release of fourth-quarter GDP data that came in better than ... Read more »

Horoscope for Friday, 1/27/23 by Christopher Renstrom

ARIES.  (March 20 – April 19):  You’ve had your fill of fair weather friends, but don’t dismiss the whole lot.  One of them will turn out to be true blue. ... Read more »

(2nd LD) Kia Q4 net jumps 63 pct on improved chip supplies, SUV demand

(ATTN: ADDS details throughout) SEOUL, Jan. 27 (Yonhap) — Kia Corp., South Korea’s second-biggest carmaker, said Friday its fourth-quarter net profit soared 63 percent from a year earlier on improved ... Read more »

Entrenador del Galaxy, Greg Vanney, afirma que club y aficionados tienen una misma meta: ganar títulos

A prácticamente un mes del debut del Galaxy ante el LAFC en el Rose Bowl de Pasadena, ha surgido un drama en las últimas semanas en el seno del equipo ... Read more »

Pacific–Briefly–Turns Neon Pink Near San Diego ‘In The Name Of Science’

Topline Portions of the Pacific Ocean turned a bright shade of neon pink this week, baffling beachgoers in La Jolla, California, although the culprit was a non-toxic dye used in ... Read more »

CCTV: Officer engulfed as he shuts door and dislodges load of snow

Police in Wisconsin issued a statement saying: "Have a safe and uneventful evening with the forecasted winter storm." Read more »

Azealia Banks endorses Ron DeSantis: Rapper says she feels 'way safer' in Miami than woke LA - and reveals she moved to Florida because the governor is 'practical' and 'focused on the basic s***'

Rapper Azealia Banks, 31, said she swapped Los Angeles for Miami because she was tired of virtue signaling in California, and respected Ron DeSantis's ruleNew York City-born Banks said that she felt safer in Miami than in LA, and felt that people in Florida 'mind their f****** business'She praised DeSantis as practical and 'focused on the basic s***', saying he prioritized basic healthcare over gender reassignment surgery Read more »

Rep. Alexandria Ocasio-Cortez Slams Republican Who Urged Her To 'Educate' Herself

Rep. Alexandria Ocasio-Cortez (D-N.Y.) went after Rep. Jeff Duncan (R-S.C.), who called on her to “educate” herself during a debate Thursday over a bill on the House floor. The Democrat ... Read more »

Orange County’s purple hue

Orange County’s purple hue IRVINE, California — Orange County was once so reliably red that then-President Ronald Reagan affectionately said the coastal enclave south of Los Angeles is “where good ... Read more »

‘Paedophilic’ man who targeted several children to face new charge involving another alleged victim

SINGAPORE – A man earlier described as a “paedophilic school bus driver” who committed sexual offences against several children will have a new charge tendered against him involving another alleged ... Read more »

Best NHL trade deadline destinations for Blackhawks star Jonathan Toews

1/26/23 The March NHL trade deadline is getting closer, which means the focus on Chicago Blackhawks star center Jonathan Toews on only going to get more intense. Toews has yet ... Read more »

A beloved Churro Vendor In Downtown Was On Her Way To Work When She Was Struck And Killed By A Drunk Driver

The incident occurred this past Sunday as Angeles Rodriguez a street vendor known for selling churros and fruit in Downtown Los Angeles was heading to work when she was struck ... Read more »

Video Captures Fight, Moment CTA Worker Shot Man Multiple Times at Red Line Station

Sylvester Adams, 53, was charged with attempted first degree murder and aggravated unlawful use of a weapon in connection with the shooting of the 37-year-old victim Read more »

Democratic Florida Senate Leader Lauren Book Introduces Bill To Ban ‘Gay/Trans Panic Defense’

FILE PHOTO: A participant holds rainbow flags at the international Rainbow Memorial Run during the inauguration of the Gay Games village at the Hotel de Ville city hall in Paris, ... Read more »

25 Arrested and Charged in Fraudulent Nursing Diploma Scheme That 'Erodes Public Trust' in South Florida

google More than 7,600 fraudulent diplomas were allegedly issued by three nursing schools in South Florida. The U.S. Department of Justice announced the arrest of 25 individuals in a statement ... Read more »

US ban on China chip exports rebounds, causes 2,700 American job losses

US ban on China chip exports rebounds, causes 2,700 American job losses California-based chipmaking kit-maker Lam hit by DRAM decline, inability to export to Middle Kingdom The Biden administration’s policy ... Read more »

Mexico gripped by ex-security chief's US drugs trial

Genaro Garcia Luna with then-US secretary of state Hillary Clinton in Mexico City in March 2009 Mexico is on tenterhooks awaiting fresh revelations from the US trial of former security ... Read more »

The Last of Us Images Spotlight Nick Offerman as a Very Different Bill

The Last of Us Images Spotlight Nick Offerman as a Very Different Bill Nick Offerman is coming to the next episode of HBO’s The Last of Us, and the actor ... Read more »

Best Alabama-Bryce Young replacements in 2023

Alabama football, Jalen Milroe Alabama did not make the College Football Playoff this past season, and that’s almost certainly going to mean extra motivation for head coach Nick Saban’s team ... Read more »

Man appears in federal court to face Capitol riot charges

FLINT, Mich. (AP) — A mid-Michigan man says he’s innocent of the charges brought against him in connection with the Jan. 6, 2021, Capitol riot in Washington. Isaac Thomas of ... Read more »

AI wildfire detection bill gets initial approval in Colorado

File—Flames rise from mountain ridges as a wildfire burns near a farmstead late Thursday, Oct. 22, 2020, near Granby, Colo. A bill is being introduced in the Colorado Legislature to ... Read more »

FDA Experts Vote to Make All COVID-19 Vaccines and Boosters Bivalent

FDA Experts Vote to Make All COVID-19 Vaccines and Boosters Bivalent In a unanimous decision, all 21 voting members of the U.S. Food and Drug Administration’s (FDA) vaccine committee recommended ... Read more »

8 biggest 401(k) mistakes to avoid

Businessman working on laptop in startup office A 401(k) can be a great way to save for retirement, but a few wrong decisions can derail your progress. Not planning or ... Read more »

'Sister Wives' Star Meri Brown Preaches To 'Look For A Way To Lift Someone Up' Amid Abuse Allegations

@therealmeribrown/instagram Sister Wives star Meri Brown took a moment to reflect on the importance of lifting people up rather than dragging them down as several of the Brown family children ... Read more »

Search underway for missing Oahu woman; case believed linked to man found dead

HONOLULU (HawaiiNewsNow) – Authorities are asking for the public’s help to find a missing woman and sources say her disappearance may be linked to a separate case in which a ... Read more »

World champion says Rubik's Cube and violin go hand in hand

World champion says Rubik's Cube and violin go hand in hand A University of Michigan student is one of the world’s foremost “speedcubers,” a person capable of quickly solving a ... Read more »

78 years on, Jewish Holocaust rescuers want their story told

78 years on, Jewish Holocaust rescuers want their story told Just before Nazi Germany invaded Hungary in March 1944, Jewish youth leaders in the eastern European country jumped into action: ... Read more »

PGA Tour news: Sam Ryder tames windy conditions to lead Farmers Insurance Open

Sam Ryder will take a three-shot lead into the third round of the Farmers Insurance Open after mastering the windy conditions at Torrey Pines on Thursday. Read more »

Trump's Attempt To Get Immunity From Jan. 6 Capitol Cop's Lawsuit Falls Flat

Trump’s Attempt To Get Immunity From Jan. 6 Capitol Cop’s Lawsuit Falls Flat Former President Donald Trump’s efforts to have a lawsuit thrown out have failed. The legal action was ... Read more »

Palestinian militants fire rockets, Israel responds with strikes in Gaza

Fire and smoke rise above buildings in Gaza City, as Israel launched air strikes on the Palestinian enclave early on Jan. 27, 2023. AFP via Getty Images JERUSALEM – Palestinian ... Read more »

‘Receding A—Hairline’: LeBron James Restrained By Ref As Heckler Loudly Attacks His Appearance

mega NBA star LeBron James had to be restrained by a referee during Tuesday night’s Lakers-Clippers game, RadarOnline.comhas learned. A video from the game showed the 38-year-old James being held ... Read more »

Texas death row inmates sue over solitary confinement

FILE – The state of Texas execution chamber in Huntsville, Texas, is pictured on May 27, 2008. A group of Texas death row inmates filed a federal lawsuit Thursday, Jan. ... Read more »

Apple's unannounced in-house chip is already reportedly going on the back burner

Apple’s unannounced in-house chip is already reportedly going on the back burner It looks like another one of Apple’s in-house chips is going on the back burner, with the company ... Read more »

3 of the Best Electric Cars According to Kelley Blue Book

Owning an EV here in America is becoming very common, as electric vehicles are slowly winning over consumers in the automotive industry. For environmentalists, an electric vehicle is a better ... Read more »
Kênh kiến thức kỹ năng, phát triển bản thân, hướng nghiệp, blog nhân sự