By Paul Sisson, The San Diego Union-Tribune

SAN DIEGO — More than 100 sites across the country are participating in recent clinical trials for a drug that shows promise for treating epileptic seizures in patients for whom other medications don't work.

The drug BHV-7000 prompts potassium receptors within the brain in a way that appears to modulate seizures, Dr. Taha Gholipour, a neurologist on the University of California, San Diego, a participant within the study and a neighborhood researcher on the study. Other commonly prescribed anti-seizure medications act on sodium and calcium channels in neurons. These routes are effective in some but not all patients.

About 40% of the estimated 1.5 million individuals with epilepsy are immune to drugs that attack the calcium and sodium pathways, meaning a 3rd pathway, via potassium, would greatly expand the choices for treating seizures.

“The potassium channel is not completely new or unknown in our neuroscience community – there have been many attempts to study this pathway in the past – but we have had no success in getting a drug that has minimal side effects and also effective seizure control,” said Gholipour. “But years of preclinical work in laboratories, in cell models, in animal models and then in early human clinical trials have shown that this drug appears to be well tolerated and effective in controlling seizures, which is exciting news.”

In a phase 1 trial, the drug was tested on 58 patients, mostly white men with a mean age of 40. It found that the fundamental unwanted effects, observed in just a handful of participants, were headaches and abdominal discomfort, which disappeared after stopping the medication.

Biohaven Ltd., a Connecticut-based biopharmaceutical company, is working to recruit 390 participants for the second and third phases of a clinical trial designed to find out whether the drug can reduce the common seizure frequency in patients diagnosed with partial-onset epilepsy Seizures may cause depression in a certain a part of the brain.

Participants have to be between 18 and 75 years old and can be randomly assigned to one in all two different dose strengths or a placebo, an inactive dose that is essential for comparison purposes. The diagnosis of focal epilepsy will need to have been made at the least one 12 months previously and participants will need to have suffered 4 or more seizures inside 28 days, have been unsuccessfully treated with at the least two anti-seizure medications, and are “on a stable” dose of at the least one and up to 3 antiepileptic drugs.”

A fentanyl vaccine developed by researchers on the University of Houston is scheduled to enter clinical trials in the course of next yr and is anticipated to supply a groundbreaking solution to a deadly crisis.

The vaccine, which has been successful in animal testing, is designed to stop the highly addictive opioid from entering the brain and causing an overdose. Biopharmaceutical startup Ovax acquired the license to fabricate and test the vaccine in November 2023 and raised over $10 million for the project by June.

“We are all incredibly excited,” said Collin GageCo-founder and CEO of the startup. He added that his company is starting “from scratch,” but he’s confident that in the future it is going to have a fentanyl vaccine available to the general public.

That day could also be a protracted time coming. While health emergencies reminiscent of the COVID-19 pandemic can speed up the event of a vaccine, can take between five and ten years — sometimes longer.

In the meantime, Fentanyl overdose deaths increase in Texasfrom lower than 80 in 2014 to almost 2,300 in 2023, in accordance with the Texas Department of State Health ServicesThe synthetic opioid – produced illegally but in addition prescription-only – is 50 times stronger than heroin and 100 times stronger than morphinemaking it the deadliest drug within the opioid crisis.

Adjuvants are crucial for fentanyl vaccines

The idea of ​​developing an opioid vaccine has scientific attention because the Nineteen SeventiesUnlike bacteria or viruses, opioids are usually not recognized by our immune systems as foreign invaders. However, the immune system could be trained to make antibodies in response to an opioid reminiscent of fentanyl. This could be achieved through a vaccine that mixes parts of the drug with non-infectious parts of bacteria and uses substances called adjuvants.

Adjuvants are designed to reinforce the immune response and are particularly necessary in vaccines against substance use disorders. Previous attempts to supply such vaccines were partly unsuccessful since the adjuvants weren’t effective enough, said Jay EvansDirector of the Center for Translational Medicine on the University of Montana. Evans can also be the scientific and strategic director of Immunea Montana-based biotech company that develops and tests quite a lot of vaccines including those aimed toward combating fentanyl and heroin addiction.

The adjuvant within the University of Houston’s fentanyl vaccine is an enterotoxin, a chemical produced by the bacteria Escherichia coli and modified to be non-infectious. It was first developed at Tulane University in Louisiana within the early 2000s and has been utilized in quite a lot of vaccines, said Colin Hailea research fellow in psychology on the University of Houston who led the event of the fentanyl vaccine. Haile can also be a co-founder and advisor to Ovax.

“It has been tested in 15 human clinical trials in combination with other vaccines,” he said, referring to the adjuvant utilized in his team's vaccine. “There have been studies in infants where the results have been fantastic, almost no side effects.”

Other researchers like David Dowling And Dr. Ofer Levyeach co-founders of Ovax, use adjuvants which have not been tested in humans but, at the very least based on animal studies, seem like effective in enhancing the immune response to vaccines against substance-related disorders, Dowling said.

Clinical trials filled with challenges

Phase 1 clinical trials for the University of Houston vaccine are expected to start within the second quarter of 2025. Ovax can also be in licensing negotiations with Boston Children's Hospital for a fentanyl vaccine developed by Dowling and Levy. If those negotiations are successful, Phase 1 clinical trials could begin in early 2026.

The aim of those studies is to find out the effectiveness of the vaccine. Safety level, possible unwanted effects and optimal dosage. Finding people to participate can be a challenge, Evans said.

“Compared to a normal infectious disease clinical trial, it's going to be more difficult. The FDA (Food and Drug Administration) is insisting that this vaccine not be tested in healthy individuals who don't already have some sort of opioid addiction,” he said. “So in Phase 1, we have to target patients who have a history of opioid use disorder, and that's a harder patient group to recruit. It's going to take longer; the patient group is going to have more side effects because they're using drugs, and they're going to be harder to follow.”

Evans added that the stigma surrounding addiction and drug use can result in people being unwilling to speak about their illness and take part in clinical trials.

Ovax has not yet decided where it is going to conduct its Phase 1 clinical trials, Gage said, but is considering sites in Australia and the Netherlands.

“We are also looking in the United States,” he said, “but it is difficult to find the right patient group.”

Future clinical trials would wish to find out the effectiveness of the vaccine to find out who would profit most and the way long immunity lasts.

Vaccines as a part of the answer

Some critics of fentanyl vaccines say they divert resources from existing treatments for opioid addiction reminiscent of buprenorphine, Methadone And NaltrexoneSome have questioned whether people would get vaccinated.

“People have to say they want a shot, and they have to decide to come back for each injection or infusion,” Keith HumphreysProfessor of Psychiatry and Behavioral Sciences at Stanford University, told the Washington Post in 2023. “The vaccines do nothing to reduce cravings or withdrawal symptoms or motivate someone to come back for further treatments.”

For Haile, a fentanyl vaccine isn’t the one solution, but one other weapon within the fight against the opioid crisis. He and his colleagues on the University of Houston have conducted animal studies to look at how the vaccine affects treatment with buprenorphine, a drug commonly prescribed to treat withdrawal symptoms and drug cravings. The results have yet to be published, but are “pretty impressive,” Haile said, noting that fentanyl vaccines could improve the effectiveness of existing treatments.

“The most important thing is that we move as quickly as possible. … We need to get something to market as quickly as possible to address this terrible problem,” Haile said. “The ultimate goal is to protect people and save lives.”

Latest technology in healthcare

Imagine the shock in case your baby was born with a swollen brain, blindness and debilitating seizures. Now imagine learning that these devastating conditions might have been prevented if you happen to had done an easy test for the common parasite. Toxoplasma gondii.

Toxoplasmosis could be transmitted anywhere an infected cat has defecated, e.g. within the litter box, sandbox, garden or yard. Other ways of infection include consuming contaminated water, undercooked meat or shellfish. In most individuals, the disease is mild and the infection could be managed.

However, if the disease occurs for the primary time while pregnant, Toxoplasmosis can go through the placenta and cause miscarriages or serious birth defects. Such transmission from mother to child while pregnant is known as congenital toxoplasmosis. Up to 4,400 babies could be born with congenital toxoplasmosis within the United States annually.

As Professor of Microbiology on the Indiana University School of Medicine I study the biology of Toxoplasmosis in my laboratory. Blood tests can monitor the amount Toxoplasmosis Antibodies within the parent. Elevated levels indicate an acute infection that puts the fetus in danger for congenital toxoplasmosis. immediate administration of antiparasitics in pregnant women who develop toxoplasmosis may help protect the fetus from the worst effects of congenital toxoplasmosis.

Several countries, including France and Austria, Testing and treating toxoplasmosis while pregnant for many years. Brazil recently launched an identical program.

However, Toxoplasmosis Tests aren’t included in prenatal screening within the US

Why should toxoplasmosis screening be performed while pregnant?

Toxoplasmosis is a widespread and insidious infection. 40 million American adults are infected with the parasite, which underlines how easy it’s to contract it. And because the infection normally doesn’t cause any obvious symptoms, can't remember when or how they were infected.

Studies conducted in several countries have shown the advantages of detecting and treating toxoplasmosis while pregnant.

The first randomized clinical trial to guage the efficacy and safety of a treatment to scale back prenatal toxoplasmosis transmission. Toxogestpublished its ends in 2018. Although the study was stopped resulting from lack of funding, the outcomes suggested that the treatment not only reduced infection transmission but in addition reduced the severity of disease in breakthrough infections.

A meta-analysis of 33 studies published between 2017 and 2021 also found that pregnant women given the antibiotic spiramycin also significantly lower parasite transmission rates to their unborn child in comparison with untreated moms.

For Dr. Jose Montoya, toxoplasmosis researcher and clinician at Remington Laboratory at Sutter Healththe advantage of screening is evident. “In countries that conduct prenatal screening for toxoplasmosis, The severity of congenital toxoplasmosis is way less than what’s routinely observed within the United States,” he said.

Congenital toxoplasmosis could also be more common than previously thought

Some argue that congenital toxoplasmosis is simply too rare to warrant prenatal testing, however the United States is currently screening for infections which can be even rarer than toxoplasmosis. comparable to phenylketonuria.

The frequency of congenital toxoplasmosis can also be underestimated. There are currently no national surveillance data on toxoplasmosis, because it shouldn’t be a nationally notifiable disease Since most states don’t monitor or report this infection while pregnant, researchers don’t understand how many miscarriages are attributable to Toxoplasmosis or what number of children suffer from the infection.

A 2021 report from the Centers for Disease Control and Prevention highlighted the Deficiencies in toxoplasmosis surveillance within the USAwhich states that routine, standardized testing while pregnant would offer vital data to evaluate the extent of this threat to babies. In addition, it could inform researchers concerning the causes of the high rate of stillbirths within the USA, the disproportionately affect black women.

Some researchers warn that Toxoplasmosis Prevalence can increases with the recognition of free-range, organically grown foods and climate change. Wild animals are more liable to infectious Toxoplasmosis Oocysts in pastures and outdoor water sources which can be more more likely to be contaminated with cat feces. Higher temperatures and stronger storms resulting from climate change promote the persistence and spread of oocysts within the environment – ​​for instance through increasing soil erosion and water pollution.

In addition, reports from unusually virulent Toxoplasmosis Tribes Migration from South America may worsen the severity of congenital toxoplasmosis infections within the United States

Costs of toxoplasmosis while pregnant

“This disease not only has enormous physical and psychological consequences, but also significant economic consequences,” said Rima McLeod is an American psychologist specializing within the treatment of Parkinson's disease. She is one among the world's leading figures and works closely with Dr. Rima McLeod.Director of the Toxoplasmosis Center on the University of Chicago.

A study McLeod conducted in 2011 estimated that adopting the French model for prenatal screening and treatment could lead to savings for U.S. taxpayers. 620 US dollars per child or 2.5 billion dollars annually.

Researchers have also developed latest technologies that reduce concerns about testing costs.

McLeod's team developed a cost-effective finger prick test that recognizes Toxoplasmosis inside half-hour. Other researchers have also found a Saliva test.

How to avoid toxoplasmosis

Toxoplasmosis causes significant, lifelong neurological and visual impairment in a whole bunch of babies born within the United States annually. Congenital toxoplasmosis could be largely mitigated by prenatal testing and treatment protocols that are protected and straightforward to perform.

“Those who conducted the clinical trial of Toxogest did not include a placebo control because it was considered unethical not to monitor and treat congenital toxoplasmosis,” Montoya said. “But currently, pregnant women in the United States are relegated to such a placebo group – deprived of simple, inexpensive procedures that could protect their children from birth defects.”

Without systematic prenatal testing for congenital toxoplasmosis, one of the best pregnant women can do is alert to risk aspectsPregnant women should avoid cleansing the litter box and other areas where cats could have done their business. Fruit and vegetables ought to be washed before consumption. Meat products ought to be cooked to the right temperature.

Health authorities are concerned about bird flu, which has thus far been detected in three dairy employees – two in Michigan and one in Texas – and in cattle in a dozen states.

The farmworkers' symptoms were mild, and researchers haven’t found that the H5N1 virus, also generally known as bird flu, could be transmitted from individual to individual. The U.S. Centers for Disease Control and Prevention says there’s little risk to the overall population. But flu viruses proceed to evolve, and H5N1 could mutate and gain the power to contaminate people more easily.

“The reason health authorities are and should be on high alert is because this is a potentially serious pathogen,” said Meghan Davis, an epidemiologist and microbiologist at Johns Hopkins University.

That's why government authorities are placing great emphasis on testing and monitoring dairy employees. But they’re facing significant challenges in doing so.

H5N1 is deadly to domestic poultry and may wipe out entire poultry flocks inside a couple of days, in accordance with the U.S. Department of Agriculture. saysThe poultry industry due to this fact responded vigorously to the threat, slaughtering entire flocks if it detected even one infected bird. In cows, nevertheless, H5N1 is milder, and the response on dairy farms has been less aggressive.

The CDC and USDA have advised dairy farms to watch for the virus in cattle and folks, but testing stays voluntary, apart from herds that move across state lines.

Dr. Amesh Adalja, an infectious disease specialist and scientist on the Johns Hopkins Center for Health Security, stressed that the present strain of bird flu doesn’t pose a pandemic threat to humans. Therefore, he said, now’s the proper time to place the suitable testing and surveillance measures in place.

“If you can't get it right with something that is as forgiving as this virus in terms of its ineffectiveness at infecting people, that really doesn't bode well for the time when there is more at stake,” Adalja said.

So far, cases of the virus have been documented in livestock in Colorado, Idaho, Iowa, Kansas, Michigan, Minnesota, New Mexico, North Carolina, Ohio, South Dakota, Texas and Wyoming. in accordance with USDALast month, federal officials announced Grants to farms to offset the fee of milk loss from sick cows. Four states – Kansas, Nebraska, New Mexico and Texas – are Start voluntary pilot programs to check dairy farms’ milk tanks for the virus.

In Michigan, where the virus was detected in 25 herdsTim Boring, director of the Department of Agriculture and Rural Development, said efforts are focused on helping farmers recoup their losses and getting them tested. Last month, the agency announced it will use a mix of federal and state funds to offer as much as $28,000 to as much as 20 affected farms.

The state also launched a study to seek out out whether antibodies are present in individuals who have had contact with sick cows, with the aim of determining whether there have been asymptomatic infections.

Dr. Natasha Bagdasarian, Michigan's chief medical officer, said the state is working with community health centers and native health departments to achieve farmworkers.

“They know not only the farms in their counties, but also many of the farmworker organizations,” she said.

Dairy farm employees, who are sometimes immigrants, cannot afford to miss a single day of labor and are due to this fact often reluctant to request a test or report that they’re feeling sick, advocates say.

“This population is just severely underserved in terms of outreach and trust in state and federal agencies,” said Elizabeth Strater, director of strategic campaigns for the United Farm Workers union. “This group of workers is some of the poorest workers in the United States.”

Immigrants make up 51% of the each day labor force on dairy farms, and farms that employ immigrants produce 79% of the country’s milk supply, in accordance with the National Association of Milk Producers.

Amy Liebman of the Migrant Clinicians Network, an education and outreach group of migrant health experts, believes the tests ought to be done on farms somewhat than in clinics.

“Dairy plants are in rural areas, very isolated geographically. You're not going to bring all the workers together in one place to do screenings or testing. You really have to try to go where the workers are,” she said.

But getting farm owners to agree hasn't been easy. The Texas Department of State Health Services told Stateline that it has offered on-site testing to farmers, but as of mid-June, it had only tested about 20 symptomatic dairy employees who volunteered to be tested. It also provided personal protective equipment to “interested dairies” and posted an ad online offering to produce the equipment.

Coordination between agriculture and health authorities on the state or local level is essential to tracking virus spread. An absence of coordination and monitoring can result in underreporting of cases.

“I think it's definitely more widespread than is currently being reported,” said Dr. Shira Doron, chief of infection control at Tufts Medicine. “The barriers between agencies are really hindering our efforts right now.”

The CDC has a payment to each farmworker who tests themselves and provides blood and nasal swab samples to the agency. But Doris Garcia-Ruiz, who directs farmworker outreach at Texas Rio Grande Legal Aid, said that won't make up for the times of lost income.

“If they take the time to go to the doctor, they don’t have sick leave and therefore don’t get paid,” she said.

The latest CDC figures show that a minimum of 53 People were tested through the outbreak of the cattle herd, with a majority of those in Michigan. Strater says that's not enough.

“This is miserable,” she said. “Our testing method is so passive. They rely on employees to report to medical clinics. These are employees who would not seek medical treatment themselves unless they were experiencing something life-threatening.”

Getting employees to make use of personal protective equipment can also be a challenge. The CDC recommends that employees wear respiratory masks, waterproof aprons and coveralls, non-ventilated safety glasses or face shields, and rubber boots with sealed seams that could be disinfected. In addition, employees are advisable to follow a selected sequence of steps at the tip of a shift to remove PPE to avoid contamination.

“Dairy work is very wet and very hands-on,” says Christine Sauvé, community engagement director on the Michigan Immigrant Rights Center. “While some industries are very familiar with PPE, the full CDC recommendation is new and different. And so that really needs to be fully encouraged by the employer and then also by state authorities.”

Sauvé worries that Michigan's response is prioritizing farmers' losses over the health of farmworkers. While the chance to the general public is low, farmworkers mustn’t be forgotten, she and other experts say.

Bethany Alcauter of the National Center for Farmworker Health described the specter of bird flu as “a kind of ticking time bomb.”

“It may not have fully worked out yet. But if we don't handle it well, it could happen,” Alcauter said.