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Inhibiting an enzyme associated with aging could help damaged nerves regrow and restore strength

Scientists at Stanford University School of Medicine and Sanford Burnham Prebys have demonstrated a new way to accelerate recovery from peripheral nerve…

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Scientists at Stanford University School of Medicine and Sanford Burnham Prebys have demonstrated a new way to accelerate recovery from peripheral nerve injury by targeting an enzyme that was thought to be responsible for muscle wasting with aging.

Credit: Blau lab, Stanford University School of Medicine

Scientists at Stanford University School of Medicine and Sanford Burnham Prebys have demonstrated a new way to accelerate recovery from peripheral nerve injury by targeting an enzyme that was thought to be responsible for muscle wasting with aging.

 

Damage to the peripheral nervous system (the nerves that form the communications network between the brain, spinal cord and body) is debilitating; the effectiveness of physiotherapy as treatment is limited. Whether from trauma, disease or aging, nerve function declines and/or is lost, resulting in diminished strength and even paralysis.

 

In the new study, published October 11, 2023 online in Science Translational Medicine and co-authored by Helen M. Blau, Ph.D., the Donald E. and Delia B. Baxter Foundation Professor at Stanford University School of Medicine, and Yu Xin Wang, Ph.D., assistant professor in the Development, Aging and Regeneration Program at Sanford Burnham Prebys, the research team found that an enzyme associated with aging is triggered by the loss of innervation.

 

Inhibiting this enzyme after nerve injury in a mouse model with a small molecule inhibitor promoted regeneration of motor nerve and formation of neuromuscular synapses that resulted in accelerated recovery of strength.

 

“Our data suggests that inhibiting the function of this particular enzyme, called 15-hydroxyprostaglandin dehydrogenase or 15-PGDH, with a small molecule boosted a naturally occurring compound (prostaglandin E2 or PGE2) in muscle tissues that helps restore nerve connectivity, function and strength,” said Wang.

 

When skeletal muscles lose nerve function, a phenomenon called denervation, they atrophy and weaken. Denervation can result from physical trauma, such as damage to nerves connecting muscles to the spinal cord, or from heritable neuromuscular wasting diseases, such as amyotrophic lateral sclerosis. Advanced age can also lead to severe muscle wasting called sarcopenia.

 

Muscle denervation and its consequences affect up to an estimated 5% of the U.S. population (approximately 17 million persons) and result in annual estimated national health care costs of $380 billion.

 

Wang was a part of Blau’s team at Stanford University, who had shown in previous research that PGE2 in muscle tissues is required for muscle stem cells to proliferate and for muscles to effectively regenerate and repair after injury.

 

The researchers have also found that 15-PGDH degrades PGE2 and that the enzyme accumulates with age. They have dubbed 15-PGDH a gerozyme — an enzyme that determines muscle wasting and which increases with aging.

 

“We wondered why this enzyme turns on with age if it has such a negative impact on muscle mass and strength,” said Wang.

 

The new work involved studying young mice using surgical methods to model injuries to the sciatic nerve. Levels of 15-PGDH rose in the denervated muscles, but pharmacological inhibition of 15-PGDH promoted subsequent motor axon growth, neuromuscular connectivity and faster recovery.

 

In studies of human tissues, the researchers detected aggregates of 15-PGDH in biopsies from a diverse range of human neuromuscular diseases, suggesting that inhibiting this enzyme could be beneficial.

 

“Restoring neuromuscular connectivity is a critical step in treating these debilitating disorders. This new approach is attractive because the treatment signals the nerve to grow back,” said Wang. “That’s why it has such a profound effect on the muscle and strength.”

 

Additional authors on the study include Mohsen A. Bakooshli, Elena Monti, Shiqi Su, Peggy Kraft, Minas Nalbandian, Ludmila Alexandrova, Joshua R. Wheeler and Hannes Vogel, all at Stanford University.

 

This study was supported by the National Institutes of Health Shared Instrumentation Grant (S100D026962); the Canadian Institutes of Health (MFE-152457); Stanford Translational Research and Applied Medicine Pilot grant; National Institutes of Health (K99NS120278, R00NS120278, R01-AG020961, R01-AG069858, R01-G009674), Stanford Dean of Research—SUMS Seed Grant Program; Donald  E. and Delia B. Baxter Foundation; the Li Ka Shing Foundation; Milky Way Research Foundation (MWRF-21664), California Institute for Regenerative Medicine (DISC2-10604).  

 

Disclosure: Authors Bakooshli, Wang and Blau are named inventors on patent application “A method to restore neuromuscular junction morphology,” assigned to Stanford University.

 

The study’s DOI is 10.1126/scitranslmed.adg1485.


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One city held a mass passport-getting event

A New Orleans congressman organized a way for people to apply for their passports en masse.

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While the number of Americans who do not have a passport has dropped steadily from more than 80% in 1990 to just over 50% now, a lack of knowledge around passport requirements still keeps a significant portion of the population away from international travel.

Over the four years that passed since the start of covid-19, passport offices have also been dealing with significant backlog due to the high numbers of people who were looking to get a passport post-pandemic. 

Related: Here is why it is (still) taking forever to get a passport

To deal with these concurrent issues, the U.S. State Department recently held a mass passport-getting event in the city of New Orleans. Called the "Passport Acceptance Event," the gathering was held at a local auditorium and invited residents of Louisiana’s 2nd Congressional District to complete a passport application on-site with the help of staff and government workers.

A passport case shows the seal featured on American passports.

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'Come apply for your passport, no appointment is required'

"Hey #LA02," Rep. Troy A. Carter Sr. (D-LA), whose office co-hosted the event alongside the city of New Orleans, wrote to his followers on Instagram  (META) . "My office is providing passport services at our #PassportAcceptance event. Come apply for your passport, no appointment is required."

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The event was held on March 14 from 10 a.m. to 1 p.m. While it was designed for those who are already eligible for U.S. citizenship rather than as a way to help non-citizens with immigration questions, it helped those completing the application for the first time fill out forms and make sure they have the photographs and identity documents they need. The passport offices in New Orleans where one would normally have to bring already-completed forms have also been dealing with lines and would require one to book spots weeks in advance.

These are the countries with the highest-ranking passports in 2024

According to Carter Sr.'s communications team, those who submitted their passport application at the event also received expedited processing of two to three weeks (according to the State Department's website, times for regular processing are currently six to eight weeks).

While Carter Sr.'s office has not released the numbers of people who applied for a passport on March 14, photos from the event show that many took advantage of the opportunity to apply for a passport in a group setting and get expedited processing.

Every couple of months, a new ranking agency puts together a list of the most and least powerful passports in the world based on factors such as visa-free travel and opportunities for cross-border business.

In January, global citizenship and financial advisory firm Arton Capital identified United Arab Emirates as having the most powerful passport in 2024. While the United States topped the list of one such ranking in 2014, worsening relations with a number of countries as well as stricter immigration rules even as other countries have taken strides to create opportunities for investors and digital nomads caused the American passport to slip in recent years.

A UAE passport grants holders visa-free or visa-on-arrival access to 180 of the world’s 198 countries (this calculation includes disputed territories such as Kosovo and Western Sahara) while Americans currently have the same access to 151 countries.

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Fast-food chain closes restaurants after Chapter 11 bankruptcy

Several major fast-food chains recently have struggled to keep restaurants open.

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Competition in the fast-food space has been brutal as operators deal with inflation, consumers who are worried about the economy and their jobs and, in recent months, the falling cost of eating at home. 

Add in that many fast-food chains took on more debt during the covid pandemic and that labor costs are rising, and you have a perfect storm of problems. 

It's a situation where Restaurant Brands International (QSR) has suffered as much as any company.  

Related: Wendy's menu drops a fan favorite item, adds something new

Three major Burger King franchise operators filed for bankruptcy in 2023, and the chain saw hundreds of stores close. It also saw multiple Popeyes franchisees move into bankruptcy, with dozens of locations closing.

RBI also stepped in and purchased one of its key franchisees.

"Carrols is the largest Burger King franchisee in the United States today, operating 1,022 Burger King restaurants in 23 states that generated approximately $1.8 billion of system sales during the 12 months ended Sept. 30, 2023," RBI said in a news release. Carrols also owns and operates 60 Popeyes restaurants in six states." 

The multichain company made the move after two of its large franchisees, Premier Kings and Meridian, saw multiple locations not purchased when they reached auction after Chapter 11 bankruptcy filings. In that case, RBI bought select locations but allowed others to close.

Burger King lost hundreds of restaurants in 2023.

Image source: Chen Jianli/Xinhua via Getty

Another fast-food chain faces bankruptcy problems

Bojangles may not be as big a name as Burger King or Popeye's, but it's a popular chain with more than 800 restaurants in eight states.

"Bojangles is a Carolina-born restaurant chain specializing in craveable Southern chicken, biscuits and tea made fresh daily from real recipes, and with a friendly smile," the chain says on its website. "Founded in 1977 as a single location in Charlotte, our beloved brand continues to grow nationwide."

Like RBI, Bojangles uses a franchise model, which makes it dependent on the financial health of its operators. The company ultimately saw all its Maryland locations close due to the financial situation of one of its franchisees.

Unlike. RBI, Bojangles is not public — it was taken private by Durational Capital Management LP and Jordan Co. in 2018 — which means the company does not disclose its financial information to the public. 

That makes it hard to know whether overall softness for the brand contributed to the chain seeing its five Maryland locations after a Chapter 11 bankruptcy filing.

Bojangles has a messy bankruptcy situation

Even though the locations still appear on the Bojangles website, they have been shuttered since late 2023. The locations were operated by Salim Kakakhail and Yavir Akbar Durranni. The partners operated under a variety of LLCs, including ABS Network, according to local news channel WUSA9

The station reported that the owners face a state investigation over complaints of wage theft and fraudulent W2s. In November Durranni and ABS Network filed for bankruptcy in New Jersey, WUSA9 reported.

"Not only do former employees say these men owe them money, WUSA9 learned the former owners owe the state, too, and have over $69,000 in back property taxes."

Former employees also say that the restaurant would regularly purchase fried chicken from Popeyes and Safeway when it ran out in their stores, the station reported. 

Bojangles sent the station a comment on the situation.

"The franchisee is no longer in the Bojangles system," the company said. "However, it is important to note in your coverage that franchisees are independent business owners who are licensed to operate a brand but have autonomy over many aspects of their business, including hiring employees and payroll responsibilities."

Kakakhail and Durranni did not respond to multiple requests for comment from WUSA9.

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Industrial Production Increased 0.1% in February

From the Fed: Industrial Production and Capacity Utilization
Industrial production edged up 0.1 percent in February after declining 0.5 percent in January. In February, the output of manufacturing rose 0.8 percent and the index for mining climbed 2.2 p…

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From the Fed: Industrial Production and Capacity Utilization
Industrial production edged up 0.1 percent in February after declining 0.5 percent in January. In February, the output of manufacturing rose 0.8 percent and the index for mining climbed 2.2 percent. Both gains partly reflected recoveries from weather-related declines in January. The index for utilities fell 7.5 percent in February because of warmer-than-typical temperatures. At 102.3 percent of its 2017 average, total industrial production in February was 0.2 percent below its year-earlier level. Capacity utilization for the industrial sector remained at 78.3 percent in February, a rate that is 1.3 percentage points below its long-run (1972–2023) average.
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Click on graph for larger image.

This graph shows Capacity Utilization. This series is up from the record low set in April 2020, and above the level in February 2020 (pre-pandemic).

Capacity utilization at 78.3% is 1.3% below the average from 1972 to 2022.  This was below consensus expectations.

Note: y-axis doesn't start at zero to better show the change.


Industrial Production The second graph shows industrial production since 1967.

Industrial production increased to 102.3. This is above the pre-pandemic level.

Industrial production was above consensus expectations.

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