No more pain

"Vertex Pharmaceuticals said its medicine could address moderate to severe acute pain, and might be able to avoid the risk of addiction.

Vertex Pharmaceuticals of Boston announced Tuesday that it had developed an experimental drug that relieves moderate to severe pain, blocking pain signals before they can get to the brain. It works only on peripheral nerves -- those outside the brain and the spinal cord -- making it unlike opioids. Vertex says its new drug is expected to avoid opioids' potential to lead to addiction.

The company reported that it had completed two randomized studies, the first in 1,118 people who had abdominoplasties and the other in 1,073 people who had bunion surgery. The two procedures are commonly used in studies of people with acute pain, the temporary kind that is brought on by something like a surgical procedure and is likely to ease with time.

In its clinical trials, Vertex measured the drug's effect with a standard pain scale in which patients rated pain severity from 1 to 10, with 10 the most severe. Those taking its drug had a statistically and clinically meaningful reduction in pain, it reports. A third study looked at safety and tolerability of the drug in people experiencing pain from a variety of conditions.

Buoyed by the results, which are yet to be published or presented at a meeting, Vertex plans to apply to the Food and Drug Administration by midyear for approval to market the drug, a pill that, for now, is called VX-548.

The company has not said when the full results and data will be made available, but scientists who were not involved in the drug's development said the information the company released was promising.

Dr. Henry Kranzler, professor of psychiatry and director of the Center for Studies of Addiction at the University of Pennsylvania's Perelman School of Medicine, called the drug "a therapeutic breakthrough."

He said its development was based on a strong body of science and, at least for acute pain, "it looks very promising" with an efficacy that, while not better than the opioid oxycodone, also is not worse.

"This has the potential to be a blockbuster," said Dr. Stephen Waxman, a professor of neurology, neuroscience and pharmacology at Yale. Dr. Waxman was not associated with the study but was paid a $1,000 speaking honorarium by the company. He predicted that the Vertex drug would be only the first foray into this new area.

"I like to think it's the beginning of nonaddictive medicines for pain," he said.

That, said Dr. James P. Rathmell, professor of anesthesia at Harvard Medical School, "is the dream all of us in this business have had for a long time."

For now, most people needing relief from moderate to severe pain have two options: drugs like ibuprofen and COX-2 inhibitors, or opioids. The drugs like ibuprofen are not very effective, and the opioids, as is well known, can be addictive because of the way they work. There is no way to separate the effects of opioids -- pain relief -- from the side effects: changes in thinking, cognition, energy and emotions.

The opioid crisis, one of the gravest public health concerns in the United States, began more than two decades ago and included people who started out taking the drugs for pain but became addicted. As states tightened regulation of prescription opioids, many turned to illegal street drugs like heroin and fentanyl. Though doctors are more cautious about prescribing opioids now, many still do so because there are few alternatives.

Efforts to develop a new class of pain-treating drugs began in earnest in the 1990s. Researchers asked if there were sodium channels that were specific for peripheral nerves. These are portals that open to send pain signals from the nerves to the brain and then close to stop transmitting. If there were portals that only controlled signals from peripheral nerves, that suggested the possibility of drugs to block them and control pain without affecting the brain, and without causing addiction. Pain might be stopped at its source.

So researchers began scouring the globe for people who had genetic mutations that prevent peripheral nerves from transmitting pain signals, or that made peripheral nerves signal pain nearly constantly. If they found those mutations, the genes involved could be targeted with drugs.

Eventually, they found both types of mutations.

In Alabama, one gene mutation caused a family to have a condition known as burning man syndrome that puts peripheral nerves into overdrive. People feel a searing pain that some have said is like hot lava inside them. Any sort of warmth can bring it on -- wearing socks or a sweater or going outside when it is 70 degrees Fahrenheit.

"It's a tragic disease," Dr. Waxman said. "It literally drives some to suicide."

After years of searching, researchers found people with a gene mutation that led to the opposite effect. The discovery began with a teenage boy in Pakistan. He made money by walking on coals or cutting himself with sharp blades in street performances. His family members had the same mutation, with "painless fractures, painless burns, painless tooth extractions and painless childbirth," Dr. Waxman said.

It's not that people with such mutations felt less pain, he said; "they did not feel any pain."

Those mutations and subsequent research led researchers to discover that two genes are needed to transmit pain, known as Nav1.7 and 1.8. The race was on to find a drug based on one of those genes.

"Every big company worked on them," said Dr. David Altshuler, chief scientific officer of Vertex Pharmaceuticals.

But it turned out to be a difficult task to find a drug that worked. Vertex, Dr. Altshuler said, spent 20 years on the project.

The result is VX-548. It inhibits Nav1.8, temporarily blocking the protein needed for the nerves to transmit pain signals.

The studies involved people with acute pain. But the company is now studying people with chronic pain from diabetic peripheral neuropathy and patients with a type of back pain, lumbosacral radiculopathy, caused by impairment or injury to a nerve in the lumbar spine.

For now, the Vertex drug, if approved, would only be used on a fairly narrow range of conditions. The greater need is for nonaddictive drugs to control chronic pain, and while studies are underway, for now only those with acute pain would benefit." [1]

If a boy in Pakistan has a protein mutation that makes him feel no pain at all, then with a good search, drugs can be found that fully replicate the effects of that mutation. So far, the drugs that replicate that mutation work, but not completely.

1. Experimental Drug Is Said to Cut Off Pain at the Source: [National Desk]. Kolata, Gina.  New York Times, Late Edition (East Coast); New York, N.Y.. 31 Jan 2024: A.15.

Premjeras žada padėti Prancūzijos ūkininkams, kol tęsiasi blokados

„Protestuotojai, blokuojantys kelius į Paryžių ir iš jo, teigiantys, kad ūkius spaudžia žemos kainos ir pernelyg didelis reguliavimas, atrodė nepajudinti ministro pirmininko Gabrielio Attalo pažadų.

 

Ministras pirmininkas Gabrielis Attal antradienį pažadėjo daugiau pagalbos Prancūzijos žemės ūkiui ir pažadėjo apsaugoti jį nuo „nesąžiningos konkurencijos“, bandydamas nuraminti protestuojančius ūkininkus, tačiau daugelis atrodė nepajudinti jo pastangų, nes jie antrai dienai blokavo pagrindinius kelius aplink Paryžių.

 

Traktorių ir šieno ryšulių užtvaros Paryžiaus regione sukėlė kilometrų ilgio eismo kliūtis, tačiau protestuotojai miesto neapsupo. Jie taip pat nesužlugdė ir pačios Prancūzijos sostinės, kuri iki šiol patyrė tik ribotus sutrikimus.

 

Vis dėlto, ūkininkai tapo augančiu spygliu Prancūzijos vyriausybei, nes ji stengiasi reaguoti į įvairius reikalavimus dėl subsidijų ūkininkavimui, aplinkosaugos taisyklių ir užsienio konkurencijos – tai tik keletas.

 

„Mūsų žemės ūkis yra turtas: ne tik todėl, kad jis maitina mus, tikrąja to žodžio prasme, bet ir todėl, kad jis yra vienas iš mūsų tapatybės ir tradicijų pamatų“, – sakė M. Attal savo pirmoje svarbioje politinėje kalboje po paskyrimo šį mėnesį.

 

„Turi būti Prancūzijos žemės ūkio išimtis“, – pridūrė jis plačiame savo vyriausybės planų pristatyme Prancūzijos parlamento žemuosiuose rūmuose, kuris buvo numatytas, prieš praėjusią savaitę prasidėjus protestams.

 

Tačiau A. Attal taip pat pripažino, kad nėra vienareikšmio atsakymo į krizę, net kai E. Macronas antradienį pažadėjo praspausti ūkininkų reikalavimus artėjančiame Europos Sąjungos viršūnių susitikime.

 

„Viskas nebus sutvarkyta per kelias savaites“, – perspėjo J. Attal.

 

Neaišku, ar ūkininkai užtvaras laikys savaites, ar tik dienas. Antradienį valdžia dėl protestų buvo priversta uždaryti ištisas mažiausiai devynių pagrindinių greitkelių atkarpas aplink sostinę, kartais net kelias mylias.

 

Protestuojantys ūkininkai taip pat blokavo kelius netoli Liono, mėtė šieną ar mėšlą priešais vyriausybinius pastatus keliuose miestuose ir trumpam užblokavo keletą prekybos centrų, apkaltintų perkant žemės ūkio produkciją pigiau už gamybos sąnaudas. Ūkininkai taip pat bandė užblokuoti prieigą prie pagrindinio Tulūzos oro uosto, padegdami šieno ryšulius.

 

Praėjusią savaitę A. Attal bandė nuraminti protestuotojus, atsisakydamas planų nutraukti valstybės subsidijas ūkininkų naudojamam kurui ir, be kitų priemonių, pažadėdamas greitesnę pagalbą galvijams, susirgusiems hemoragine liga, kuri neseniai užklupo pietvakarius.

 

Antradienį J. Attal paskelbė keletą naujų pranešimų. Jis žadėjo, kad uždelstos Europos ūkininkavimo subsidijos bus išmokamos iki kovo 15 d., galvijų augintojai gaus naujų mokesčių lengvatų, o vynuogių augintojai iki savaitės pabaigos gaus skubios pagalbos paketą. Vyriausybė artimiausiomis dienomis paskelbs papildomas priemones, pridūrė jis.

 

Tačiau tai beveik nepajudindavo besibarikaduojančių protestuotojų.

 

„Daug nesitikėjau“, – sakė ūkininkas Cyrille Milardas, auginantis grūdus maždaug 50 mylių į pietryčius nuo Paryžiaus, Senos ir Marnos regione.

 

„Žinome, kad iš karto negausime visų atsakymų į savo reikalavimus“, – sakė jis. „Tačiau yra dalykų, kuriuos vyriausybė gali padaryti nedelsiant“, – pridūrė jis, pavyzdžiui, dar labiau sumažinti biurokratines taisykles, nors pripažino, kad dėl kai kurių taisyklių galima derėtis tik ES. lygiu.

 

P. Milardas, pagrindinės Prancūzijos ūkininkų sąjungos Senos ir Marnos skyriaus pirmininkas, kalbėjo telefonu iš savo automobilio, kai 100 traktorių vilkstinę vedė atgal į barikadą A5 greitkelyje, jungiančiame Paryžių į rytus nuo Prancūzija, po trumpo įsiveržimo arčiau sostinės.

 

Pasak jo, prie užtvaros yra apie 350 ūkininkų, turinčių apie 250 traktorių, jie organizavo maitinimą ir miegamąsias zonas, reguliariai gauna pastiprinimą iš kitų regionų. Aplink Paryžių, 5–25 mylių atstumu nuo sostinės, yra maždaug 8 panašios barikados.

 

„Jie trokšta kovos“, – sakė p. Milardas. „Sunku juos sustabdyti greitkelyje“.

 

Pagrindinės ūkininkų sąjungos paragino ramius protestus. Tačiau tai strategijai meta iššūkį mažesnės, radikalesnės grupės. Kai kurie siūlė sutrikdyti didmeninę maisto rinką Rungio mieste, esančiame į pietus nuo Paryžiaus – vieną didžiausių Europoje ir esminį sostinės regiono maisto šaltinį.

 

Valdžia jau dislokavo šarvuotas policijos mašinas, kad užkirstų kelią bet kokiems įsibrovimams. Policijos pajėgos taip pat bandė atidėti maždaug 200 traktorių vilkstinę, kuri pirmadienį išvyko iš pietvakarių Prancūzijos su Rungiu.

 

Protestuotojai dabar laukia ketvirtadienį Briuselyje prasidėsiančio Europos Sąjungos viršūnių susitikimo, kuriame E. Macronas turėtų daryti lobizmą Prancūzijos ūkininkų vardu.

 

E. Macronas savo pirmame plačiame viešame pareiškime nuo protestų pradžios antradienį pareiškė, kad pykčio sprendimui reikia „ne mažiau Europos, o kartais daugiau Europos“, pažymėdamas, kad ES subsidijos ūkininkavimui buvo svarbus Prancūzijos ūkininkų pajamų komponentas.

 

 „Kaltinti dėl visko Europą būtų per lengva“, – sakė jis per spaudos konferenciją Stokholme, kur buvo su valstybiniu vizitu.

 

Tačiau E. Macronas taip pat sakė, kad ketvirtadienį susitiks su ES prezidente Ursula von der Leyen. Komisija aptars ES lygmens sprendimus dėl ūkininkavimo protestų, kurie šį mėnesį taip pat kilo Vokietijoje, Ispanijoje ir Belgijoje.

 

Pavyzdžiui, daugelis prancūzų ūkininkų prieštarauja laisvosios prekybos susitarimui, dėl kurio šiuo metu derasi blokas ir Mercosur, Pietų Amerikos šalių aljansas, nes, jų teigimu, nėra pakankamai garantijų, kad šios šalys turės taikyti tokias pačias aplinkosaugos ir sanitarijos priemones ir Europos ūkininkų standartus. Prancūzija jau seniai nepritarė dabartiniam susitarimui, tačiau Prancūzijos ūkininkų sąjungos nori, kad jis būtų visiškai panaikintas.

 

Macronas sakė, kad reikalaus „aiškumo“ dėl Mercosur-E.U. susitarimas, kuris, jo teigimu, neturėtų būti pasirašytas, kaip dabar rašoma; primygtinai reikalauti, kad būtų imtasi „aiškių priemonių“ dėl padidėjusio Ukrainos paukštienos ir grūdų importo, kuris, jo teigimu, sukėlė trikdžių Europos maisto produktų rinkose; ir prašyti lankstesnių tam tikrų Europos aplinkosaugos taisyklių. [1]

 

1. Prime Minister Vows to Aid French Farmers as Blockades Persist: [Foreign Desk]. Breeden, Aurelien.  New York Times, Late Edition (East Coast); New York, N.Y.. 31 Jan 2024: A.10.

Prime Minister Vows to Aid French Farmers as Blockades Persist

"Protesters blocking roads in and out of Paris, who say farms are squeezed by low prices and excessive regulation, seemed unmoved by promises from Prime Minister Gabriel Attal.

Prime Minister Gabriel Attal promised more aid for French agriculture on Tuesday and vowed to shield it from "unfair competition" in an attempt to appease protesting farmers, but many appeared unmoved by his efforts as they blocked major roads around Paris for a second day.

The barricades of tractors and bales of hay caused miles of traffic bottlenecks in the Paris region, but protesters have not encircled the city. Neither have they crippled the French capital itself, which has experienced only limited disruptions so far.

Still, the farmers have become a growing thorn in the French government's side as it struggles to respond to a wide-ranging mix of demands on farming subsidies, environmental regulations and foreign competition -- to name only a few.

"Our agriculture is an asset: not only because it feeds us, in the truest sense of the word, but because it is one of the foundations of our identity and traditions," Mr. Attal said in his first major policy speech since his appointment by President Emmanuel Macron this month.

"There must be a French agricultural exception," he added in a wide-ranging presentation of his government's plans before France's lower house of Parliament, an appearance scheduled before the protests spread last week.

But Mr. Attal also acknowledged that there was no one-size-fits-all answer to the crisis, even as Mr. Macron vowed on Tuesday to press the farmers' demands at an upcoming European Union summit.

"Everything will not be fixed in several weeks," Mr. Attal warned.

Whether farmers will keep up their barricades for weeks or merely days is unclear. On Tuesday the authorities were forced to close off whole sections of at least nine major highways around the capital because of the protests, sometimes for several miles.

Protesting farmers also blocked roads near Lyon, dumped hay or manure in front of government buildings in several towns, and briefly blocked a handful of supermarkets accused of buying farm produce under its production costs. Farmers also tried to block access to the main airport serving Toulouse by setting bales of hay on fire.

Last week Mr. Attal had tried to appease the protesters by scrapping plans to end state subsidies for fuel used by farmers and by vowing more rapid aid for cattle sickened by a hemorrhagic disease that recently hit the southwest, among other measures.

On Tuesday Mr. Attal made a handful of new announcements. Delayed European farming subsidies will be paid out by March 15, he promised, cattle farmers will get new tax breaks, and wine growers will get an emergency aid package by the end of the week. The government will announce additional measures in the coming days, he added.

But that did little to budge the barricading protesters.

"I didn't expect much," said Cyrille Milard, a farmer who grows grain about 50 miles southeast of the Paris, in the Seine-et-Marne region.

"We know we won't get all the answers to our demands right away," he said. "But there are things that the government can do immediately," he added, like cutting back even more bureaucratic regulations, though he acknowledged some rules could only be negotiated at the E.U. level.

Mr. Milard, the president of the Seine-et-Marne chapter of France's main farmers union, spoke on the phone from his car as he led a 100-tractor convoy back to a barricade on the A5 highway that connects Paris to the east of France, after a brief incursion closer to the capital.

About 350 farmers are at the barricade with about 250 tractors, he said, and have organized meals and sleeping areas, with regular reinforcements from other regions. There are about 8 or so similar barricades around Paris, within 5 to 25 miles of the capital.

"They're eager for a fight," Mr. Milard said. "It's hard to keep them at a standstill on a highway."

Mainstream farmers' unions have urged calm protests. But that strategy is being challenged by smaller, more radical groups. Some have suggested disrupting the wholesale food market in Rungis, just south of Paris -- one of the largest in Europe, and a crucial source of produce for the capital region.

The authorities have already deployed armored police vehicles there to head off any incursions. Police forces have also tried to delay a convoy of about 200 tractors that left southwestern France on Monday with Rungis in its sights.

Protesters are now looking ahead to a European Union summit that starts on Thursday in Brussels, where Mr. Macron is expected to lobby on behalf of French farmers.

Mr. Macron, in his first extensive public statement since the start of the protests, said on Tuesday that the solution to the anger was "not less Europe, it is sometimes more Europe," noting that the E.U.'s farming subsidies were a crucial part of French farmers' income.

"Blaming everything on Europe would be too easy," he said at a news conference in Stockholm, where he was on a state visit.

But Mr. Macron also said he would meet on Thursday with Ursula von der Leyen, the president of the E.U. Commission, to discuss E.U.-level solutions to the farming protests, which have also erupted this month in Germany, Spain and Belgium.

Many French farmers, for instance, are opposed to a free-trade agreement currently being negotiated between the bloc and Mercosur, an alliance of South American countries, because they say there not enough guarantees that those countries will have to apply the same environmental and sanitary standards as European farmers. France has long opposed the deal in its current form, but French farming unions want it to be scrapped entirely.

Mr. Macron said he would demand "clarity" on the Mercosur-E.U. deal, which he said should not be signed as it now reads; press for "clear measures" on increased Ukrainian poultry and grain imports, which he said had caused disruptions on European food markets; and ask for more flexibility on certain European environmental regulations.” [1]

1. Prime Minister Vows to Aid French Farmers as Blockades Persist: [Foreign Desk]. Breeden, Aurelien.  New York Times, Late Edition (East Coast); New York, N.Y.. 31 Jan 2024: A.10.