MeiraGTx's gene therapy improves motor function, quality of life in phase 2 Parkinson's trial

 MeiraGTx is looking to march its Parkinson’s disease treatment forward into phase 3 after the gene therapy improved motor ability and quality of life in a small midphase trial. 

A total of 14 patients were given a one-time infusion of either a high or low dose of the therapy, dubbed AAV-GAD, or a sham treatment into their subthalamic nucleus, a brain region that plays a pivotal role in motor control. AAV-GAD delivers a gene that codes for the enzyme that makes the neurotransmitter GABA, which is implicated in the characteristic motor dysfunction of Parkinson’s. 

All the patients had idiopathic Parkinson’s, meaning the cause of their disease is unknown, and had a yearlong history of responsiveness to levodopa, a biological precursor to the neurotransmitter dopamine. 

At Week 26, the high-dose group had improved by an average of 18 points on the motor function section of the Unified Parkinson's Disease Rating Scale, MeiraGTx said in an Oct. 15 release. There was no statistically significant improvement in the low dose or sham treatment arms.

In a 39-question survey of quality of life called the Parkinson’s Disease Questionnaire, low-dose patients improved by an average of 6 points from baseline at 26 weeks, while high-dose patients improved by 8 points.

“We have now treated a total of 58 patients in this development program in three independent multicenter clinical studies and have seen no [serious adverse events] related to AAV-GAD treatment,” MeiraGTx President and CEO Alexandria Forbes, Ph.D., said in the release. Even with small patient numbers, she said, “AAV-GAD treatment results in significant and clinically meaningful changes in key efficacy endpoints in Parkinson’s disease.”

Dopamine replacement therapy with levodopa is a common treatment for Parkinson’s, but the drug can lose effectiveness over time as the disease continues to progress. AAV-GAD is meant to reprogram brain circuits with a one-time treatment to correct the effects of low dopamine.

“These data demonstrate the impact of using highly targeted local delivery of gene-based therapy to correct the aberrant circuitry that results from the depletion of dopamine in the brain of idiopathic Parkinson’s patients,” Forbes added in the release.

The company is now discussing with regulators in the U.S., Europe and Japan about initiating a phase 3 trial, Forbes said. Patients who completed the phase 2 study also have the option to enroll in a longer-term follow up.

MeiraGTx has already seen some Big Pharma interest, with Sanofi investing $30 million in the New York-based biotech last year for a first look at the company's new data from its range of programs in immunology, inflammation, central nervous disorders and metabolic diseases. At around the same time, MeiraGTx presented preclinical findings showing that its gene therapy for amyotrophic lateral sclerosis prevented the loss of motor neurons in rat and mouse models of the disease. 

MeiraGTx wholly owns its own manufacturing facilities in London and Shannon, Ireland, and has an internally developed end-to-end manufacturing process.

https://www.fiercebiotech.com/biotech/meiragtx-gene-therapy-improves-motor-function-and-quality-life-phase-2-parkinsons-trial

 Eli Lilly is expanding its innovation digs to Beijing, China, opening two research centers called the Eli Lilly China Medical Innovation Center and Lilly Gateway Labs. 

The newest Gateway Lab is the second to set up shop outside of the U.S. following a recently announced European branch planned in the U.K. The innovation incubators employ a flexible partnership model that allows researchers to lease space and take advantage of Lilly’s resources and expertise during the drug development process.

So far, more than 20 biotechs have used the facilities and more than 50 therapies are being developed at the labs, according to Lilly.

Other than the new international locations, Lilly operates two Gateway Labs in San Francisco and one in Boston, with a permanent location in San Diego planned for next year.

The new set-ups in Beijing will “further deepen Eli Lilly’s century-old business layout in China," Chief Scientific Officer and president of Lilly research laboratories Daniel Skovronsky, M.D., Ph.D. said in an Oct. 15 release.

“The new center will enable us to explore new clinical research designs to accelerate patient access to breakthrough therapies," Skovronsky added, while the Gateway Lab will “provide office space and research strategy guidance for domestic start-up biotechnology companies to help them develop a new generation of drugs for patients. "

Lilly plans to register its Beijing Medical Innovation Center as an independent legal entity, according to the company. The drugmaker’s work in China stretches back to 1918, when it established a Shanghai office. These days, Lilly employs more than 3,200 staffers in China.

Just recently, the company put $200 million toward an expansion of its sole manufacturing spot in China to bolster production of type 2 diabetes and obesity meds Mounjaro and Wegovy. The newest investment will add 120 new jobs to the plant and brings Lilly’s total investment in the Suzhou site to nearly 15 billion yuan ($2.1 billion).

Lilly isn’t the only drugmaker planting innovation roots in China. Last month, Bayer opened the doors to its own life science incubator in the Shanghai Innovation Park, the latest in a line of external innovation facilities that also operate in Japan, Germany and the U.S. 

https://www.fiercebiotech.com/biotech/eli-lilly-expands-innovation-reach-another-global-gateway-lab-time-china

Supreme Court opens door to Texas online journalist's lawsuit over her 2017 arrest

 The Supreme Court on Tuesday ordered a federal appeals court to take a new look at the lawsuit filed by a Texas-based online citizen journalist who said she was wrongly arrested in a case that drew attention from national media organizations and free speech advocates.

The justices tossed out the ruling of a divided federal appeals court that found journalist Priscilla Villarreal, known online as La Gordiloca, could not sue police officers and other officials over her arrest for seeking and obtaining nonpublic information from police.

The high court directed the 5th U.S. Circuit Court of Appeals to review Villareal's case in light of the Supreme Court's ruling in June in another case from Texas. In June, the justices gave a former local elected official another chance to pursue her lawsuit claiming she too was wrongly arrested.

In that case, Sylvia Gonzalez, a former city council member in the San Antonio suburb of Castle Hills, said she was arrested in retaliation as part of a dispute with a political rival.

A state judge had previously dismissed the criminal case against Villareal, saying the law used to arrest her in 2017 was unconstitutional. She then sought to sue the officials for damages. The full 5th Circuit ruled 9-7 that officials Villarreal sued in Laredo and Webb County were entitled to legal immunity.

Villarreal had sought — and obtained from a police officer — the identities of a person who killed himself and a family involved in a car accident and published the information on Facebook. The arrest affidavit said she sought the information to gain Facebook followers.

https://www.yahoo.com/news/supreme-court-opens-door-texas-140301431.html

US judge orders Boeing, DOJ to detail diversity policy before deciding on plea

 A federal judge on Tuesday ordered Boeing and the U.S. Justice Department to detail the impact of diversity and inclusion policies on the selection of an independent monitor before he decides whether to accept the planemaker's plea deal.

U.S. District Judge Reed O'Connor held a hearing Friday as he considers whether to approve Boeing's agreement to plead guilty to conspiring to defraud regulators. The deal would include oversight for three years by an independent monitor.

The order is the latest hurdle Boeing faces to avoid a potentially embarrassing trial and plead guilty to misleading the Federal Aviation Administration and violating a 2021 deferred prosecution agreement.

O'Connor on Tuesday told DOJ and Boeing to answer questions by Oct. 25 about the DOJ policy of selecting a monitor in keeping with the government's commitment to diversity and inclusion.

A DOJ spokesperson said the government "will comply with the judge’s order and respond before the court’s deadline." Boeing did not immediately comment.

While ordering DOJ and Boeing to respond to a series of questions about the diversity and inclusion policy and how it might affect the selection of an independent monitor, he also pointed out that it was not a disputed facet of the plea agreement.

"Critically, Boeing did not voice any objection to this provision," the judge said in his order.

O'Connor also wants the planemaker to detail how its existing diversity, equity and inclusion policies "are used in its current compliance and ethics efforts."

The planemaker agreed to pay up to a $487.2 million fine and spend at least $455 million on improving safety and compliance practices over three years of court-supervised probation as part of the plea deal.

O'Connor Friday pressed the Justice Department to justify the terms of Boeing's agreement to plead guilty to fraud in the wake of the two fatal 737 MAX crashes in Indonesia in 2018 and Ethiopia in 2019 that killed 346 people.

Attorneys for Boeing and DOJ argued Judge O'Connor should accept the plea deal, while lawyers for relatives of the crash victims urged him to reject it. Boeing agreed in July to plead guilty to conspiring to defraud regulators.

https://www.usnews.com/news/top-news/articles/2024-10-15/us-judge-orders-boeing-doj-to-detail-diversity-policy-before-deciding-on-plea

Boeing lines up $35 billion in funds as strike hammers finances

 Boeing set out to shore up its sagging finances on Tuesday, announcing plans to raise up to $25 billion through stock and debt offerings and a $10 billion credit agreement with major lenders amid a production and regulatory crisis.

It was not clear when and how much the planemaker would eventually raise, but analysts estimate Boeing needs somewhere between $10 billion and $15 billion to maintain its credit ratings, which are now just one notch above junk.

Boeing has lurched from crisis to crisis this year, kicking off on Jan. 5 when a door panel blew off a 737 MAX jet in mid-air. Since then, its CEO departed, its production has been slowed as regulators investigate its safety culture, and in September, 33,000 union workers went on strike.

The company is looking to shore up its finances with a cash-and-debt raise as it faces the possibility that its credit rating will be lowered after three straight quarters of burning through cash.

The strike is costing roughly $1 billion a month, according to one analyst estimate, and to reduce costs the planemaker has also said it would cut 17,000 jobs.

The company's shares were up 2.1% on Tuesday.

S&P Global and Fitch warned of a downgrade last month. The ratings agencies said on Tuesday that the stock and debt sales could help preserve Boeing's investment-grade rating.

"The supplemental credit facility also seems like a sensible precaution," S&P Global's Ben Tsocanos said.

However, some analysts were not convinced.

"We take the vagueness and breadth of the shelf announcement and the need for the temporary financing as implying that the banks are struggling to sell this issue to potential investors or lenders," said Agency Partners analyst Nick Cunningham, who suspended his recommendation and price target for Boeing's shares.

Boeing said on Tuesday it had not drawn on the new $10 billion credit facility, arranged by BofA, Citibank, Goldman Sachs and JPMorgan, or its existing revolving credit facility.

"These are two prudent steps to support the company's access to liquidity," Boeing said, adding that the potential stock and debt offerings will provide options to support its balance sheet over a three-year period.

On Monday, Emirates Airlines President Tim Clark became the first senior industry figure to articulate fears over Boeing's ability to tackle its worst-ever crisis intact.

https://finance.yahoo.com/news/boeing-files-registration-statement-securities-105152746.html

Georgia Judge Rules County Officials Can't Delay, Decline To Certify Election Results

 by Samantha Flom via The Epoch Times (emphasis ours),

A Georgia judge has ruled that county election officials must certify election results by the statutory deadline regardless of irregularities or suspected fraud.

Fulton County Superior Judge Robert McBurney in Atlanta on May 2, 2022. Ben Gray/AP Photo

Georgia law requires county election superintendents to certify election results by 5 p.m. on the Monday following the election—or the Tuesday, if the date falls on a federal holiday, as it does this year.

Fulton County Superior Court Judge Robert McBurney ruled on Oct. 14 that election officials must stick to that deadline.

“No election superintendent (or member of a board of elections and registration) may refuse to certify or abstain from certifying election results under any circumstance,” the judge wrote in his opinion.

McBurney added that if a superintendent should determine a need for additional information from the elections board or other election officials, that information should be provided “promptly,” where unprotected by law.

“However, any delay in receiving such information is not a basis for refusing to certify the election results or abstaining from doing so,” he wrote.

Julie Adams, a Republican member of the Fulton County Board of Elections and Registrations, brought the lawsuit after the county’s appointed election director allegedly denied her repeated requests for access to election results and processes.

“Plaintiff swore an oath to ‘prevent fraud, deceit, and abuse’ in Fulton County elections and to ‘make a true and perfect return,’” Adams’s attorneys wrote in the initial complaint. “These obligations are frustrated by the repeated and continuing refusal to allow Plaintiff access to, and direct knowledge of, the information Plaintiff reasonably believes she needs to execute her duties faithfully and thoroughly.”

Unable to observe the county’s election results and processes herself, Adams voted against certifying the results of the presidential preference primary in March. Her lawsuit sought clarification of the extent of the election director’s role and her own rights as a member of the election board.

In his ruling, McBurney held that election certification is “a purely ministerial task that gives its performer no discretion to exclude some votes while counting others.”

He reasoned that allowing election superintendents to “play investigator, prosecutor, jury, and judge” and refuse to certify results “because of a unilateral determination of error or fraud” would effectively silence Georgia voters.

“Our Constitution and our Election Code do not allow for that to happen,” he concluded.

McBurney’s latest ruling coincided with the start of early voting in the Peach State. Voters will have the option to vote early in person through Nov. 1.

https://www.zerohedge.com/political/georgia-judge-rules-county-officials-cant-delay-decline-certify-election-results

Unseen Cost of Weight Loss and Aging: Tackling Sarcopenia

 Losses of muscle and strength are inescapable effects of the aging process. Left unchecked, these progressive losses will start to impair physical function. 

Once a certain level of impairment occurs, an individual can be diagnosed with sarcopenia, which comes from the Greek words "sarco" (flesh) and "penia" (poverty). Individuals with sarcopenia have a significant increase in the risk for falls and death, as well as diminished quality of life. 

Muscle mass losses generally occur with weight loss, and the increasing use of glucagon-like peptide-1 (GLP-1) medications may lead to greater incidence and prevalence of sarcopenia in the years to come.

A recent meta-analysis of 56 studies (mean participant age, 50 years) found a twofold greater risk for mortality in those with sarcopenia vs those without. Despite its health consequences, sarcopenia tends to be underdiagnosed and, consequently, undertreated at a population and individual level. Part of the reason probably stems from the lack of health insurance reimbursement for individual clinicians and hospital systems to perform sarcopenia screening assessments. 

In aging and obesity, it appears justified to include and emphasize a recommendation for sarcopenia screening in medical society guidelines; however, individual patients and clinicians do not need to wait for updated guidelines to implement sarcopenia screening, treatment, and prevention strategies in their own lives and/or clinical practice. 

Simple Prevention and Treatment Strategy

Much can be done to help prevent sarcopenia. The primary strategy, unsurprisingly, is engaging in frequent strength training. But that doesn't mean hours in the gym every week. 

With just one session per week over 10 weeks, lean body mass (LBM), a common proxy for muscle mass, increased by 0.33 kg, according to a study which evaluated LBM improvements across different strength training frequencies. Adding a second weekly session was significantly better. In the twice-weekly group, LBM increased by 1.4 kg over 10 weeks, resulting in an increase in LBM more than four times greater than the once-a-week group. (There was no greater improvement in LBM by adding a third weekly session vs two weekly sessions.) 

Although that particular study didn't identify greater benefit at 3x/week compared with 2x/week, the specific training routines and lack of a protein consumption assessment may have played a role in that finding. 

Underlying the diminishing benefits, a different study found a marginally greater benefit in favor of performing ≥ 5 sets per major muscle group per week compared with < 5 sets per week for increasing muscle in the legs, arms, back, chest, and shoulders. 

Expensive gym memberships and fancy equipment are not necessary. While the use of strength training machines and free weights have been viewed by many as the optimal approach, a recent systematic review and meta-analysis found that comparable improvements to strength can be achieved with workouts using resistance bands. For those who struggle to find the time to go to a gym, or for whom gym fees are not financially affordable, resistance bands are a cheaper and more convenient alternative. 

https://www.medscape.com/viewarticle/unseen-cost-weight-loss-and-aging-tackling-sarcopenia-2024a1000inn