#Alzheimer's drug

[ruthlesslistener]

Gotta say, PETA deciding to set up their anti-animal testing demonstration the week I started working (I care for lab rodents being used to develop medicines) is kind of an unfortunate coincidence.

[warningsine]

Federal health authorities on Tuesday gave approval to an experimental new drug that has shown to delay the onset of Alzheimer’s disease in trials.

Donanemab, manufactured by Eli Lilly, is the second medication that has won the blessing of the Food and Drug Administration (FDA) to treat patients showing early symptoms of the disease, most prominently cognitive impairment.

Last year, authorities cleared the drug lecanemab, marketed under the brand name Leqembi, after it demonstrated a similar decline in the progression of Alzheimer’s in a control group.

The treatments are not a cure, but the first to physically alter the course of the disease rather than just addressing its symptoms, the FDA said.

Indianapolis-based Eli Lilly reported the success of its trial a year ago, and subsequently applied for the FDA authorization that was announced today. Experts at the time said it “could be the beginning of the end of Alzheimer’s disease”, which affects almost 7 million people, mostly older Americans, according to the Alzheimer’s Association.

“Kisunla demonstrated very meaningful results for people with early symptomatic Alzheimer’s disease, who urgently need effective treatment options,” Anne White, executive vice-president of Eli Lilly said on Tuesday, referring to donanemab by the brand name it will be sold under.

“We know these medicines have the greatest potential benefit when people are treated earlier in their disease, and we are working hard in partnership with others to improve detection and diagnosis.”

According to Eli Lilly, Kisunla slowed cognitive and functional decline by up to 35% after 18 months, compared to patients who took a placebo. It also reduced participants’ risk of progressing to the next clinical stage of the disease by up to 39%, the company said.

Taken by infusion every four weeks, the monoclonal antibody works by targeting deposits of amyloid protein in the brain, a key indicator of the presence of Alzheimer’s.

The drug “can help the body remove the excessive buildup of amyloid plaques and slow the decline that may diminish people’s ability to remember new information, important dates, and appointments; plan and organize; make meals; use household appliances; manage finances; and be left alone”, an Eli Lilly statement said.

Kisunla will be expensive, with each vial costing almost $700 and a year’s course expected to be $32,000, according to Lilly’s calculation. But the Centers for Medicare and Medicaid Services announced last year it planned to cover new Alzheimer’s drugs approved by the FDA, as long as physicians maintained a rigid record of their performance.

It also comes with some risk, the FDA said. Side effects include potential brain swelling or bleeding, but those were reportedly mild in patients during the late-stage trial of 1,700 people. Three deaths were also attributed to the drug, but ultimately the FDA, which delayed approval in March for further evaluation, decided the benefits outweighed any risk.

Side effects were similar to those reported in Leqembi.

“Diagnosing and treating Alzheimer’s sooner than we do today has the potential to meaningfully slow disease progression, giving patients invaluable time to maintain their independence for longer,” said Dr Howard Fillit, co-founder and chief science officer at the Alzheimer’s Drug Discovery Foundation, in the Lilly statement.

“This approval marks another step forward in evolving the standard of care for people living with Alzheimer’s disease that will ultimately include an arsenal of novel treatments, providing much needed hope to the Alzheimer’s community.”

[reasonsforhope]

“The first drug to slow the destruction of the brain in Alzheimer's has been heralded as momentous.

The research breakthrough ends decades of failure and shows a new era of drugs to treat Alzheimer's - the most common form of dementia - is possible.

Yet the medicine, lecanemab, has only a small effect and its impact on people's daily lives is debated.

And the drug works in the early stages of the disease, so most would miss out without a revolution in spotting it.

Lecanemab attacks the sticky gunge - called beta amyloid - that builds up in the brains of people with Alzheimer's.

For a medical field littered with duds, despair and disappointment, some see these trial results as a triumphant turning point.

Alzheimer's Research UK said the findings were "momentous.”

One of the world's leading researchers behind the whole idea of targeting amyloid 30 years ago, Prof John Hardy, said it was "historic" and was optimistic "we're seeing the beginning of Alzheimer's therapies." Prof Tara Spires-Jones, from the University of Edinburgh, said the results were "a big deal because we've had a 100% failure rate for a long time..."

The large-scale trial involved 1,795 volunteers with early stage Alzheimer's. Infusions of lecanemab were given every fortnight.

The results, presented at the Clinical Trials on Alzheimer's Disease conference in San Francisco and published in the New England Journal of Medicine, are not a miracle cure. The disease continued to rob people of their brain power, but that decline was slowed by around a quarter over the course of the 18 months of treatment.

The data is already being assessed by regulators in the US who will soon decide whether lecanemab can be approved for wider use. The developers - the pharmaceutical companies Eisai and Biogen - plan to begin the approval process in other countries next year.” -via BBC, via Future Crunch, 12/1/22

[ausetkmt]

New Alzheimer's drugs bring hope. But not equally for all patients.

https://www.washingtonpost.com/health/2024/01/29/alzheimers-new-drugs-black-patients-leqembi/

ABINGTON, Pa. — Wrapped in a purple blanket, Robert Williford settles into a quiet corner of a bustling neurology clinic, an IV line delivering a colorless liquid into his left arm.

The 67-year-old, who has early Alzheimer’s disease, is getting his initial dose of Leqembi. The drug is the first to clearly slow the fatal neurodegenerative ailment that afflicts 6.7 million older Americans, though the benefits may be modest. The retired social worker, one of the first African Americans to receive the treatment, hopes it will ease his forgetfulness so “I drive my wife less crazy.”

But as Williford and his doctors embark on this treatment, they are doing so with scant scientific data about how the medication might work in people of color. In the pivotal clinical trial for the drug, Black patients globallyaccounted for only 47 of the 1,795 participants — about 2.6 percent. For U.S. trial sites, the percentage was 4.5 percent.

The proportion of Black enrollees was similarly low for Eli Lilly Alzheimer’sdrug, called donanemab, expected to be cleared by the Food and Drug Administration in coming months. Black people make up more than 13 percent of the U.S. population.

The paltry data for the new class of groundbreaking drugs, which strip a sticky substance called amyloid beta from the brain, has ignited an intense debate among researchers and clinicians. Will the medications — the first glimmer of hope after years of failure — be as beneficial for African Americans as for White patients?

“Are these drugs going to work in non-Whites? And particularly in Blacks? We just don’t have enough data, I don’t think,” said Suzanne E. Schindler, a clinical neurologist and dementia specialist at Washington University in St. Louis. “In general, the default is that they will work the same in everybody, but we don’t really know that for sure.”

The situation casts a spotlight yet again on the decades-long failure of researchers to reflect the increasingly diverse character of the patient population in the United States, and underscores the stark disparities in Alzheimer’s treatment and care. Black Americans develop the disease and related dementias at twice the rate of their White counterparts, but are less likely to receive specialized care and are diagnosed at later stages, studies show. That’s an urgent problem considering that the new drugs must be used early to have an effect.

In addition, a perplexing new issue appears to be contributing to low Black enrollment in trials and is fueling a debate among experts about the role of race, genetics and other factors. To qualify for the main trial for Leqembi — developed by the Japanese pharmaceutical giant Eisai and the biotechnology company Biogen of Cambridge, Mass. — participants were required to have elevated levels of brain amyloid, a defining characteristic of Alzheimer’s, and symptoms such as memory loss.

But brain scans showed that the African American volunteers were less likely to have excess amyloid than White patients and thus were excluded from the trial at higher rates. Almost half of Black applicants failed to meet the amyloid threshold, compared with 22 percent of White volunteers, according to Eisai. A similar pattern occurred with the Lilly drug and in some other studies, and sometimes involved other people of color, including Hispanics.

Experts are baffled by the findings. Why would amyloid levels — thought to be a key driver of Alzheimer’s — be different in people with similar cognitive problems?

“Is it the color of someone’s skin? Almost certainly not,” said Joshua D. Grill, an Alzheimer’s researcher at the University of California at Irvine. “Is it a difference in genetics? Or other health conditions, like cholesterol, blood pressure or vascular health? Or is it something else, that we haven’t measured?”

While the biology of Alzheimer’s is almost surely the same regardless of race, some researchers say the patients themselves might be different because of underlying health conditions. Some older Black patients diagnosed with Alzheimer’s, they say, might actually have vascular dementia stemming from heart disease, hypertension and diabetes — all conditions more prevalent among African American patients.

The risk of vascular damage also could be increased by a lack of access to health care and years of exposure to racism, as well as genetics, some experts say. And many patients could have a constellation of pathologies driven by other factors, they add.

Whatever the cause, experts say, the bottom line is the same: Patients who do not have excessive amounts of the sticky brain protein should not be treated with the amyloid-targeting drugs because the therapies are unlikely to work and pose substantial risks, including potentially deadly bleeding in the brain.

But that raises the specter of another disparity. If it turns out that a lower proportion of Black dementia patients and other people of color have excess amyloid, they could be left behind as the drug industry races to develop amyloid-reducing treatments. To counter that, experts are urging companies to accelerate work addressingother potential drivers of cognitive decline and to develop combination drugs with multiple targets.

“If we are just targeting amyloid, we can just miss a large potential population that might benefit from treatment,” said Lisa L. Barnes, a neuropsychologist at Rush University in Chicago.

‘A brain is a brain’

For now, the question remains: What should Black patients and their doctors think about the anti-amyloid drugs?

The answer, experts say, depends largely on the level of amyloid in their brains.

More than a year ago, Williford was diagnosed with early Alzheimer’s by David C. Weisman, a neurologist at Abington Neurological Associates, a large practice north of Philadelphia that treats patients and conducts clinical trials for drug companies. The clinic was one of the test sites for Leqembi.

After Leqembi receivedfull FDA approval last summer, Williford underwent tests to determine whether he was a good candidate for the drug. One test — a lumbar puncture, sometimes called a spinal tap — showed elevated amyloid in his brain. That means Williford and similar patients are likely to benefit from an anti-amyloid medication regardless of their race or ethnicity, Weisman and several other experts said.

“A brain is a brain is a brain, whether it is Asian, Hispanic, African American or White,” Weisman said. “A patient is either a good fit or a bad fit, and Robert is a good fit.”

Williford, who spent years working with troubled families in Philadelphia, began having memory problems a few years ago, said his wife, Cynthia Byron-Williford, 59.

“You could tell him almost anything, and he would almost immediately forget,” she said. “If I asked him to make a peanut butter sandwich for our grandson, he would come back three times and say, ‘What am I supposed to do?’”

With few treatment options, many physicians say they will offer anti-amyloid therapy to any patient who has elevated levels of the substance and passes safety tests.

Barry W. Rovner, a neurology professor at Thomas Jefferson University in Philadelphia, said he would not hesitate to offer Leqembi to African American patients who tested positive for amyloid. But, he added, because of the low numbers of Black individuals in the Leqembi trial, “I would say, ‘Look, this has not been tried in many Black people, so we don’t know precisely how it is going to work. But you don’t know precisely how it will work in any person.’”

From a research perspective, “You could say, as a group we don’t know if Black individuals respond the same way to anti-amyloid drugs because we don’t have the data,” Washington University’s Schindler said. “But on an individual level, it is different. If I had a Black patient who was amyloid-positive, I would start him on these drugs.”

But some Black patients might not be comfortable with the medication.

Zaldy S. Tan, director of the memory disorders center at Cedars-Sinai Medical Center in Los Angeles, said when African American patients are informed about the risks and benefits of Leqembi, and about the sparse data available for Black individuals, some will “take a pause and question whether they are willing to accept the uncertainty” and challenges of receiving the every-other-week infusion and multiple follow-up tests.

A promise of diversity

The best way to know for sure how drugs for Alzheimer’s — and other diseases — affect different populations is to have more diversity in trials, experts agree. But research participation by Black Americans and other people of color has been held down for years for several reasons.

The 20th century’s infamous Tuskegee syphilis study created long-standing mistrust about trials within the African American community. Men were left untreated to suffer and die even after an effective treatment emerged for the bacterium.

Alzheimer’s research, meanwhile, has long been centered in memory clinics at elite academic institutions, which tend to attract well-heeled patients with health insurance and other resources. The clinics have served as effective recruiting grounds for trials that end up with a predominantly White enrollment.

“We have done a poor job of making African American Alzheimer’s research inclusive,” said John Morris, a neurologist at Washington University in St. Louis. More than two decades ago, he created an African American advisory board at the school’s Knight Alzheimer Disease Research Center after realizing only 3 percent of trial participants were Black.

Others also are redoubling efforts to increase diversity. John Dwyer, president of the Global Alzheimer’s Platform Foundation, a nonprofit that runs trials, said the organization has sharply increased participation by people of color by sending dedicated teams of African American and Latino professionals into communities to build relationships with physicians and personnel at health centers, senior centers and places of worship. They stress to the communities how much they can benefit from the studies, he said.

Stephanie Monroe, vice president and senior adviser of health equity and access at the advocacy group UsAgainstAlzheimer’s, noted that low Black enrollment is not limited to Alzheimer’s trials. If all the drugs that have not been tested on people of color were eliminated, the shelves of pharmacies would be nearly empty, she said.

“That doesn’t work when you are almost a 50-50 minority/majority population,” Monroe said.

The FDA has issued guidelines for industry designed to bolster diversity in studies, while the National Institute on Aging recently pledged toprioritize funding requests that are “appropriately inclusive.”

The low Black enrollment in studies is just the latest controversy involving the anti-amyloid drugs. For years, earlier versions of the drugs failed repeatedly in trials. By contrast, Leqembi, in an 18-month trial, showed unambiguous, if modest, benefits, slowing disease progression by about 27 percent, or roughlyfive months. The drug, administered every other week, carries a list price of $26,500 a year.

In July, Lilly reported that its anti-amyloid drug, donanemab, was even more effective at removing amyloid. But like Leqembi, it can cause serious side effects, including brain hemorrhages. Some doctors think the drugs will provide bigger benefits when taken for a longer period or earlier in the disease, but others say the medications, which require repeated MRIs to check for side effects, leave much to be desired.

Both Eisai and Lilly said they are working hard to increase diversity in clinical trials. In the meantime, they said, patients with elevated amyloid should benefit from the anti-amyloid drugs, regardless of race or ethnicity.

“We have no pathophysiological reason to expect different efficacy between races and ethnicities for Alzheimer’s treatments that remove amyloid,”Lillysaid in a statement.

Eisai acknowledged that the Leqembi trial was not designed to test the drug in individual racial and ethnic subgroups. But it said in a statement that the totality of the evidence indicated that “all patients, regardless of ethnicity, benefited from treatment” with the drug.

“We and the U.S. FDA — as evidenced by the agency’s approval of Leqembi — believe that the benefits and risks in these patient populations and races has been established,” the company added. Eisai said volunteers who did not pass the amyloid threshold did not have Alzheimer’s and should be assessed for other conditions.

In an interview, Teresa Buracchio, acting director of the FDA’s Office of Neuroscience, said the agency “did not see a notable difference by race” in safety and effectiveness in the limited data available on subgroups in the Leqembi trial.

But other experts were skeptical, saying the number of Black patients in the Leqembi trial was too low to know whether the medication is safe and effective for African Americans. “Without having a representative population, it is impossible to assess,” said Barnes, of Rush University.Some researchers suggested that patients in underrepresented populations should wait for future advances in treatment.

‘We just want to get going’

On a recent day, nurse Christine Besso bustled in and out of Williford’s infusion room at the neurology clinic, taking his vital signs and inserting an IV line. “Let’s get this party started,” she said.

Byron-Williford, watching the process from a nearby couch, said she was not concerned about the low numbers of African Americans in the Leqembi trial.

“I think it will work or not work based on the individual,” she said, adding with a laugh, “and if it doesn’t work for him, it is because he is ornery.”

Byron-Williford said her husband’s health problems accelerated a few years ago after his son, who was in his early 20s, died unexpectedly. Williford became depressed and lost his appetite. Last summer, when he went to pick up his wife at a nearby hair salon, he drove around, lost. She later confiscated his car keys.

In the clinic, shortly after Williford’s infusion began, Weisman stopped in to check on him and discuss possible side effects. When Williford asked him how long he would be on the drug, Weisman shrugged, saying it depended on how he did on the drug and on test results.

“We are getting on an airplane, and we don’t even have a destination airport yet,” Weisman said. “We just want to get going.”

[vanx-97]

When did you stop being yourself?

Do I know you? I can't tell

Sometimes you are familiar

Other times you are someone else

[decompose1]

what if i took a bunch of dxm and listened to all of Everywhere at the End of Time. that sounds like a really good idea

[quotesfrommyreading]

For decades, nursing homes have been using drugs to control dementia patients. For nearly as long, there have been calls for reform.

In 1987, President Ronald Reagan signed a law banning the use of drugs that serve the interest of the nursing home or its staff, not the patient.

But the practice persisted. In the early 2000s, studies found that antipsychotic drugs like Seroquel, Zyprexa and Abilify made older people drowsy and more likely to fall. The drugs were also linked to heart problems in people with dementia. More than a dozen clinical trials concluded that the drugs nearly doubled the risk of death for older dementia patients.

In 2005, the Food and Drug Administration required manufacturers to put a label on the drugs warning that they increased the risk of death for patients with dementia.

Seven years later, with antipsychotics still widely used, nursing homes were required to report to Medicare how many residents were getting the drugs. That data is posted online and becomes part of a facility’s “quality of resident care” score, one of three major categories that contribute to a home’s star rating.

The only catch: Antipsychotic prescriptions for residents with any of three uncommon conditions — schizophrenia, Tourette’s syndrome and Huntington’s disease — would not be included in a facility’s public tally. The theory was that since the drugs were approved to treat patients with those conditions, nursing homes shouldn’t be penalized.

The loophole was opened. Since 2012, the share of residents classified as having schizophrenia has gone up to 11 percent from less than 7 percent, records show.

The diagnoses rose even as nursing homes reported a decline in behaviors associated with the disorder. The number of residents experiencing delusions, for example, fell to 4 percent from 6 percent.

  —  Phony Diagnoses Hide High Rates of Drugging at Nursing Homes

[angelnumber27]

s moke some heroin

no dumbass I’m off opiates and have been for a loooong time lol 🫶🏻🖕🏻

[trendynewsnow]

Cassava Sciences Terminates Alzheimer’s Drug Trial Due to Disappointing Results

Cassava Sciences Halts Alzheimer’s Drug Trial Amid Disappointing Results Cassava Sciences, a small but ambitious biotechnology firm headquartered in Austin, Texas, has made the significant decision to terminate its advanced clinical trial for simufilam, an experimental drug aimed at treating Alzheimer’s disease. This development comes as the company seeks regulatory approval for a treatment that…

[jeeses]

Explore the Alzheimer’s Disease pipeline drugs market, including key drugs in development, market drivers, challenges, and future opportunities. Gain insights into the latest advancements and competitive landscape shaping Alzheimer’s treatments.

Market Overview and Current Landscape (200 words)

Overview of Alzheimer’s Disease: Outline the prevalence and impact of AD globally.

Current Treatment Limitations: Discuss the limited efficacy of current treatments and the need for new therapies.

Growth Drivers: Mention factors like aging populations, rising diagnosis rates, and investment trends.

2. Key Pipeline Drugs and Mechanisms of Action (400 words)

Amyloid-Beta and Tau Therapies: Explain the role of amyloid-beta plaques and tau tangles in Alzheimer’s pathology.

Neuroprotective and Neuroinflammatory Drugs: Describe drugs targeting inflammation and neuroprotection.

Symptomatic vs. Disease-Modifying Therapies: Differences and the potential impact of each.

3. Technological and Diagnostic Advancements (300 words)

Biomarkers: How biomarkers are enhancing early diagnosis and tracking disease progression.

Digital Health and Remote Monitoring: Innovations improving trial outcomes and patient engagement.

[camifornilla]

There isn’t a single trial or research study that’s ever getting off the ground from the Private Practice or Grey’s Anatomy hospitals because they can’t fucking help but be messy as hell in their private lives and bring that on the job with them

[neurodiscoveryai]

6 Debilitating Neurological Disorders and the Search for Potential Cures

This article discusses six neurological disorders which presently have no definite cure. Also, how AI is being used to find new treatments for these diseases. These disorders are Multiple Sclerosis (MS), Parkinson’s Disease (PD), Alzheimer’s Disease (AD), Frontotemporal Dementia (FTD), Migraine and Autism Spectrum Disorders (ASD).

Multiple sclerosis (MS) is a neurological disorder which affects the central nervous system (CNS). For a patient suffering from MS, their immune system attacks myelin (protective cover of nerve fibers) by mistake. It causes cognitive impairment, paralysis, numbness, blurred vision, coordination problems and fatigue. There is a serious need for new drug discovery approaches as there is no complete cure available. NeuroDiscovery AI is using artificial intelligence to make advances in helping to find cures for MS.

The company uses real world data (RWD) like EHRs (electronic health records) and treatment outcomes to analyze disease progression and treatment efficiency. Their AI platform analyzes huge medical datasets to help in patient recruitment and designing effective clinical trials. This assists biotech researchers and pharmaceutical companies to identify potential drug candidates. The platform collaborates with neurological care providers, academic institutions and life sciences companies to provide large patient datasets. It is leading to a complete transformation of the MS drug discovery process as artificial intelligence is continuously evolving.

Parkinson's disease (PD) is a progressive CNS disorder which largely affects movement. This occurs with the degeneration of nerve cells in substantia nigra (a part of the brain). These nerve cells create dopamine which is a neurotransmitter crucial for coordinated and smooth muscle movement. Patients go through symptoms like balance issues, slowness of movement, stiffness, tremors, sleep disturbances, cognitive decline, changes in speech and depression. 

PD is supposed to be caused by trauma, environmental and genetic factors. The treatments for PD are limited to managing symptoms and improving the quality of life as there is no cure available for PD. NeuroDiscovery AI is on a mission to help in finding cures for PD with its extensive patient data and use of its AI platform.

Alzheimer’s disease (AD) is a neurodegenerative disease which impacts behavior, thinking and memory. AD is the most prevalent reason for dementia. AD starts with moderate memory loss which becomes worse gradually. This leads to cognitive impairment and decreases the patient's ability in carrying out day-to-day activities.

AD begins with symptoms like difficulties in learning new things, remembering recent events, confusion and memory loss. With its progression, patients experience mood swings, impaired judgment, trouble in speaking and disorientation. The patient loses the ability for basic communication, daily tasks and recognizing close ones. AD is supposed to be caused by lifestyle, environmental, genetic and age factors. At present, treatments for AD focus on managing symptoms, improving quality of life for patients and slowing disease progression. NeuroDiscovery AI envisions a world where AD can be stopped and even reversed.

Frontotemporal dementia (FTD) is a category of CNS disorders which affects the frontal and temporal lobes in the brain. This leads to changes in motor skills, personality and overall behavior in patients. There are three primary types of FTD, Behavioral variant FTD (bvFTD), Primary progressive aphasia (PPA) and FTD with movement disorders.

bvFTD is the degeneration in the frontal lobe which results in personality changes. PPA mainly affects a patient's language skills. PPA patients lose fluency in speaking, have problems in sentence forming and have difficulties in finding the correct words. FTD with movement disorders have motor symptoms like movement issues, tremors and stiffness which are similar to symptoms found in ALS (amyotrophic lateral sclerosis) and PD. We at NDAI are assisting life sciences companies in neuro research to find a cure for FTD.

Migraine is the most common CNS disorder which can be described by repeated headaches of different intensities. It impacts a patient's quality of life and daily activities. The other symptoms which follow migraine are auras (visual disturbances), nausea (urge to vomit), phonophobia (sensitivity to sound) and photophobia (sensitivity to light). Generally, a migraine attack advances in four phases, Prodrome, Aura, Headache and Postdrome. All patients may not experience all four phases.

Prodrome is the first phase occurring hours/days before headache which has symptoms like neck stiffness, mood swings, fatigue and food cravings. Aura has symptoms like flashing lights, blurred vision, tingling sensations and blind spots. Aura usually lasts for less than an hour. The headache phase has intense pain mostly on one side of the head which lasts between 4 hours to 3 days. This phase is also followed by symptoms like sensitivity to sound/light, nausea and vomiting. Postdrome is the last phase which lasts up to 2 days. The symptoms include fatigue, weakness, confusion and exhaustion. NDAI is working towards finding innovative cures for Migraine.

Autism Spectrum Disorder (ASD) is a neurological condition which impacts social interaction, behavior, communication ability, forming relationships and maintaining eye contact. Most often, ASD occurs by the early age of 2-3. ASD is believed to be caused by a combination of environmental and genetic factors. People with mild ASD symptoms lead independent lives. While others with major symptoms need support in daily tasks.

ASD is usually followed by symptoms like sensitivities to sound and light. This affects a person's daily life in a significant way. ASD treatment includes medical treatment, nutritional therapy, social skills training, school based therapies, occupational therapy, sensory integration therapy, behavioral therapy and cognitive therapy.

NeuroDiscovery AI is partnering with top healthcare providers, educational institutions, patient advocacy groups and life sciences companies to transform neurology with AI driven insights.

[gu6chan]

Your post about The Most American Sandwhich just made me imagine Leonard as an American... Leonard scuttling about at a Walmart parking lot, trying to fit all the food he bought in the trunk (enough to hermit away for the next few weeks begote he has to restock again)

this is a bit late but this has me WAILING........ american leonard, what groceries will he buy........ do you think he would treat him also to The Most American Sandwich

now introducing: the U.P's youngest resident

also during the process of scribbling in his hoodie i looked at it and almost started crying

[vanx-97]

I don't know how much longer it will be

I don't think you're ready to leave

From the stars above to the oceans beneath

There's still so much you need to see

This life we live is bitter sweet

It isn't always what we dream

There's some things we just can't keep

I just wish you could stay here with me

-By Me

[reasoningdaily]

Science: Did a top NIH official manipulate Alzheimer's and Parkinson’s studies for decades?

In 2016, when the U.S. Congress unleashed a flood of new funding for Alzheimer’s disease research, the National Institute on Aging (NIA) tapped veteran brain researcher Eliezer Masliah as a key leader for the effort. He took the helm at the agency’s Division of Neuroscience, whose budget—$2.6 billion in the last fiscal year—dwarfs the rest of NIA combined.

As a leading federal ambassador to the research community and a chief adviser to NIA Director Richard Hodes, Masliah would gain tremendous influence over the study and treatment of neurological conditions in the United States and beyond. He saw the appointment as his career capstone. Masliah told the online discussion site Alzforum that “the golden era of Alzheimer’s research” was coming and he was eager to help NIA direct its bounty. “I am fully committed to this effort. It is a historical moment.”

Masliah appeared an ideal selection. The physician and neuropathologist conducted research at the University of California San Diego (UCSD) for decades, and his drive, curiosity, and productivity propelled him into the top ranks of scholars on Alzheimer’s and Parkinson’s disease. His roughly 800 research papers, many on how those conditions damage synapses, the junctions between neurons, have made him one of the most cited scientists in his field. His work on topics including alpha-synuclein—a protein linked to both diseases—continues to influence basic and clinical science.

But over the past 2 years questions have arisen about some of Masliah’s research. A Science investigation has now found that scores of his lab studies at UCSD and NIA are riddled with apparently falsified Western blots—images used to show the presence of proteins—and micrographs of brain tissue. Numerous images seem to have been inappropriately reused within and across papers, sometimes published years apart in different journals, describing divergent experimental conditions.

After Science brought initial concerns about Masliah’s work to their attention, a neuroscientist and forensic analysts specializing in scientific work who had previously worked with Science produced a 300-page dossier revealing a steady stream of suspect images between 1997 and 2023 in 132 of his published research papers. (Science did not pay them for their work.) “In our opinion, this pattern of anomalous data raises a credible concern for research misconduct and calls into question a remarkably large body of scientific work,” they concluded.

Neither Masliah nor the various drug companies, universities, or federal ­agencies that were provided the dossier have so far rejected or challenged any of its examples of possible misconduct despite being given the material more than 2 weeks ago. And today, the National Institutes of Health (NIH) released a statement saying that following an investigation, it had “made findings of research misconduct” against Masliah for “falsification and/or fabrication involving re-use and relabel of figure panels” in two publications. According to the statement, Masliah no longer serves as NIA’s neuroscience division director, but NIH declined to further clarify his employment status.

Masliah and Hodes, via a spokesperson, declined to reply to detailed questions, provide an interview, or comment on the dossier. NIH Director Monica Bertagnolli also declined to comment. And Masliah did not reply to Science’s requests for raw images and other data related to the examples in suspect papers, or to a new request for comment on the NIH misconduct finding.

The dossier challenges far more studies than the two cited in NIH’s statement, including many that underpin the development and testing of experimental drugs (see sidebar). Masliah’s work, for example, helped win a nod from the U.S. Food and Drug Administration (FDA) for clinical trials of an antibody called prasinezumab for Parkinson’s. Made by Prothena—a company backed by big money—the drug is intended to attack alpha-synuclein, whose build up in the brain has been linked to the condition’s debilitating physical and cognitive symptoms.

But in a trial of 316 Parkinson’s patients, reported in 2022 in The New England Journal of Medicine, prasinezumab showed no benefit compared with a placebo. And volunteers given infusions of the antibody suffered from far more side effects such as nausea and headaches than those in a placebo group who received sham infusions. Prothena is now collaborating in another trial of the drug candidate involving 586 Parkinson’s patients.

The creators of the dossier, who were unaware of NIH’s probe when they spoke with Science, emphasize that they are not themselves accusing Masliah or his colleagues of fraud or misconduct. They note that some of the identified image problems might have been simple errors, and that when images are prepared for publication, some can acquire innocent visual artifacts that resemble improper changes. Distinguishing the two sometimes requires comparison to raw, high-resolution images and other data, which the dossier’s authors did not have. But they say their findings merit formal investigations.

The enormity of apparent problems described in the Masliah dossier stunned 11 neuroscientists who agreed to review it for Science. “Breathtaking,” says neuroscientist Christian Haass of the Ludwig Maximilian University of Munich. “People will, of course, be shocked, as I was. … I was falling from a chair, basically.”

He and the other researchers didn’t personally verify every example of possible misconduct, but they agreed that most of the suspect work cannot reasonably be explained as careless errors or publishing anomalies. “I’m floored,” says Samuel Gandy, a prominent neurologist at the Mount Sinai Alzheimer’s Disease Research Center who was visibly shaken during a video interview. “Hundreds of images. There had to have been ongoing manipulation for years.”

Gandy was disturbed, for example, that Masliah and colleagues seem to have used the same image of a mitochondrion, a cellular energy-producing structure, in two articles on different topics published 2 years apart in different journals. “The bus driver could see that they are identical,” Gandy says.

MASLIAH IS THE SOLE common author on every paper in the dossier, usually taking the first or last position in multiauthor articles. Those positions imply he did the majority of the publication’s work or bears primary responsibility for it, although the others contributed.

Several of the neuroscientists who reviewed the dossier say it seems implausible that Masliah was duped by a colleague. “Given the extended time frame and huge number of differing collaborators and co-authors on these papers, [possible misconduct] by a rogue postdoc or a collaborating scientist doesn’t apply here,” says Tim Greenamyre, director of the University of Pittsburgh Institute for Neurodegenerative Diseases. “I have a hard time believing that he didn’t know, whether he changed the images himself or somebody else did so on his behalf.”

I’m floored ... Hundreds of images. There had to have been ongoing manipulation for years.

Samuel Gandy

Mount Sinai Alzheimer’s Disease Research Center

At a minimum, according to neuroscientists who spoke with Science, the large volume of doubtful images erodes trust in Masliah’s overall body of work. All 11 who reviewed the dossier agree that all his problem papers should be investigated by NIH, scholarly journals, funders, and UCSD. The university declined to comment, and NIH did not say whether it planned or was conducting a broad misconduct investigation into his research. Masliah this week, days after NIH said it concluded its probe, still appeared with Hodes, the NIA director, to give introductory remarks at the start of a national Alzheimer’s summit on the NIH campus.

As a division director, Masliah would hold sway over NIA’s neuroscience funding, according to Alan Leshner, who previously led two other NIH institutes and headed AAAS (publisher of Science) until 2015. In most cases, he says, institutes select grants based on scores awarded by peer-review “study sections.” But institute and division directors can fund preferred projects, such as studies of amyloid, the brain protein linked to Alzheimer’s disease, over better scoring competitors.

“There’s no question that in most cases, a division director … is viewed as someone who has the judgment to set priorities,” Leshner says. They can also alter the direction of a field. If a division director shows interest in a particular aspect of neuro-science related to aging, he adds, “you get [many] proposals in the next round in that area.”

There’s no evidence that Masliah has been a poor steward of NIA’s neuroscience budget or directed it down blind alleys underpinned by suspect data, but NIH’s statement today still leaves many crucial questions unaddressed.

“The volume of papers and resources involved are enormous—as is Dr. Masliah’s leadership and influence on the field, including drug development pipelines,” says Vanderbilt University neuroscientist Matthew Schrag, one of those who helped assemble the dossier. “That makes it a very influential example of possible misconduct.”

MASLIAH, 65, TRAINED in medicine and neuropathology at the National Autonomous University of Mexico (UNAM), earning his medical degree in 1982 and completing a residency in pathology in 1986. He married a U.S. resident who also studied medicine at UNAM. They relocated to San Diego after Masliah’s training.

Soon after, he landed a plum research fellowship in the lab of Robert Terry, a titan in neuropathology and Alzheimer’s research who reportedly received NIH’s first grant for the neurodegenerative condition in the 1960s. “I was incredibly lucky to meet Dr. Bob Terry,” he told a UCSD interviewer in 2016. In a 1990 photo of Terry’s lab staff, a dark-bearded, youthful Masliah stands proudly, arms folded and wearing his trademark large glasses, beside his famous mentor, who died in 2017. Terry and Masliah pioneered the use of an optical imaging method known as confocal microscopy to create high-resolution 3D images of brain cells.

Masliah went on the lead UCSD’s Experimental Neuropathology Laboratory, where he contributed to early work on alpha-synuclein and novel antibody and vaccine approaches to attack Alzheimer’s and ­Parkinson’s—some of which led to experimental drugs such as prasinezumab that have reached human trials. For Parkinson’s, he also explored antidepressants, and anti-inflammatory drugs or compounds. And for Alzheimer’s, he looked into compounds to decrease the production of amyloid, which builds up in the brain and forms deposits known as plaques outside neurons.

Neurologist Douglas Galasko, who formerly directed the UCSD Alzheimer’s Disease Research Center, where Masliah worked, praises his scholarship and character, calling him “highly collegial and very hardworking.” Galasko co-authored five papers in the dossier, making modest contributions unrelated to apparently doctored images. (He opted not to view the document.)

Galasko says he never heard concerns or doubts about Masliah, whom he describes as “very serious, yet warm and thoughtful, and engaging to have a conversation with.” Those qualities earned him long-term loyalty from investigators working in his lab, Galasko adds. “He’s a very effective spokesperson, organizer, and synthesizer of ideas.” Colleagues at UCSD, he notes, felt enormous pride when Masliah took the helm at NIA’s neuroscience division.

Major impact

Eliezer Masliah’s research on Parkinson’s and Alzheimer’s diseases has enjoyed global influence. His output, as well as the number of citations to his papers, place him among the world’s top 10 scientists in certain subfields (highlighted in red).

“NIA sets the agenda worldwide for age-related diseases,” says Scott Ayton, who directs a neuroscience center at the Florey research institute in Australia, echoing peers in the U.S. and Europe. He was among those who reviewed the dossier and considered the concerns highly credible.

University of Texas at San Antonio neuroscientist George Perry, chief editor of the Journal of Alzheimer’s Disease, describes Masliah’s research as influential and well-regarded, as do other experts in neurodegenerative diseases. In key topics related to Alzheimer’s and Parkinson’s, Masliah frequently ranks in the global top 10 researchers—and often first—by number of papers and citations to them, according to an analysis of data from Dimensions Analytics, a scholarly research data bank from the U.K. company Digital Science (see chart, above). For example, Masliah placed first for papers that use the terms “synuclein” and “synapse.”

His most influential work includes fundamental studies of synaptic damage in mice genetically engineered to mimic various neurodegenerative conditions. “People are very dependent on all of these descriptions,” says Perry, who also reviewed the dossier on Masliah’s research for Science. Many are among the 132 questioned papers, which have racked up more than 18,000 citations, often by leading scholars. “Now I think that work was probably fabricated, in part,” Perry adds, calling the influence of the questioned papers “very problematic.”

BEGINNING IN 2023, forensic image sleuths began to flag a few papers in which Masliah played a central role, posting to PubPeer, an online forum where research publications are discussed and allegations of misconduct often raised. In a few cases, Masliah or a co-author replied or made corrections. Soon after, Science spotted the posts, and because of Masliah’s position and standing decided to take a deeper look.

Schrag, Columbia University neurobiologist Mu Yang, and independent forensic image analyst Kevin Patrick agreed to examine a wider swath of Masliah’s output. (Patrick, a nonscientist who uses the moniker “Cheshire” on social media, had pseudonymously submitted several PubPeer posts on Masliah papers.) In 2023, after a similar request from Science, the same group had assessed work by University of Southern California (USC) Alzheimer’s and stroke expert Berislav Zlokovic. Their dossier of possible misconduct and a subsequent Science report prompted university and NIH investigations, which are apparently ongoing, and led NIH to pause a late-stage clinical trial of a stroke drug based in part on apparently manipulated studies.

For the new dossier, Schrag provided examples, technical context, and expertise on how the findings might affect the promise of prasinezumab and other drugs. Yang took the lead role in identifying and examining questionable images. She used Image- twin, a software program, to assist her own personal scrutiny. (The software, for example, initially spotted the reused mitochondrion image.) Schrag and Yang worked independently of their employers.

Microbiologist and research integrity expert Elisabeth Bik, who also worked on the Zlokovic dossier, contributed other Masliah examples and reviewed and concurred with almost all of the findings. All of the dossier authors worked as volunteers, poring over papers and images in their spare time. The group says it will post many of the examples from the Masliah dossier on PubPeer for others to review; Schrag provided the dossier to NIH, as did Science in the course of producing this story. (NIH’s statement says it had initiated its own investigation much earlier, in May 2023, after receiving allegations from the HHS Office of Research Integrity [ORI].)

In Yang’s analysis of multiple Masliah-authored papers, duplicated sections in some Western blots that had been “seamlessly blended” quickly floated into view, she says. “It tells me someone put a lot of thought and effort into the image … and usually indicates something is very wrong.”

Yang began to see patterns in the apparent image doctoring, which also included images that had been duplicated or seemingly altered by “cloning” portions of them. “I started feeling like a curator or art historian—when you look at a piece of art without the label, you know the artist by the style. Like a painting from Picasso’s blue period,” she adds, “it’s a signature style that I saw in many, many papers—the way they lay out the figures, even the color contrast.”

After finding hundreds of questionable images, the group had more than enough strong signs of misconduct and stopped looking, Yang says. But she suspects similar problems would emerge from a close examination of the hundreds of other Masliah papers.

Making a drug look better?

National Institute on Aging neuroscience chief Eliezer Masliah was senior author of a 2015 study of the Alzheimer’s disease treatment Cerebrolysin in BMC Neuroscience. Brain-tissue images from normal mice and mice engineered to overexpress a mutant form of the tau protein might have been doctored to suggest the drug reduces damage from the tau.

Overlapping copies

In the paper, normal (non-tg) mice show no tau damage. The mutant mice (3RTau) show tau damage unless treated with Cerebrolysin. But a merged image of the younger, normal mouse and the older, treated mutant appear unnaturally similar. Yellow sections are identical.

A series of clones

Dissimilar (red or green) areas within the merged image seem to be caused by efforts to obscure the duplication. Small “cloned” areas within each image are indicated by same-color boxes. The journal’s publisher said it would review the concerns.

YANG AND THE OTHER authors say the ongoing human trials of prasinezumab add to the urgency of their findings. According to Prothena, the drug blocks the spread of toxic alpha-synuclein and might slow the progression of Parkinson’s movement disorders and dementia. Prasinezumab’s documented side effects have not been dangerous. But if it is based on suspect scientific foundations and, as the first clinical results suggest, ineffective, further clinical testing could raise false hopes and divert patients from trials of other experimental drugs.

The concept for prasinezumab emerged from Masliah’s ties to the late Dale Schenk, a UCSD-trained neuroscientist whose research helped pioneer the idea of treating Alzheimer’s and Parkinson’s with vaccines designed to block the buildup of harmful amyloid and synuclein. Masliah, Schenk, and others proposed that immunizing people with benign parts of each protein could spur the immune system to produce antibodies that might block the full, toxic form. Infusing labmade antibodies might have the same effect. Either approach, they hypothesized, could offer a “disease modifying” attack on a condition’s root cause, rather than merely alleviating symptoms.

In a 2016 post on Alzforum, Masliah recalled an early discussion with Schenk on the idea. “Dale and I sat at a coffee shop (his favorite place) next to the Pacific Ocean and drew, on a napkin, the concept of how a potential synuclein vaccine might work,” he said. “People strongly doubted the potential use of a vaccine approach in Alzheimer’s and even more so in Parkinson’s. Dale was one of the few who listened and believed in the idea.”

To pursue that vision Schenk co-founded and served as chief executive of Prothena, spun off in 2012 from the former biopharma company Elan. Masliah worked extensively with Schenk until his death from pancreatic cancer at age 59 in 2016. Four of their joint studies, published between 2005 and 2017, proved foundational for prasinezumab, according to Prothena’s promotional material. Schenk was senior author on two of the papers, Masliah on two. All four used apparently doctored images, according to the dossier, as did other Masliah papers cited in clinical trial reports as important to prasinezumab’s development. Some of the papers suggested Parkinson’s symptoms could be generated in mice engineered to produce alpha-synuclein, and that those symptoms could be reduced by injecting antibodies akin to prasinezumab into the animals.

Greenamyre, a Parkinson’s specialist, says the papers showed an “astonishing level” of apparent image manipulation. But he notes that the image anomalies and the drug’s lack of success so far don’t necessarily mean “that synuclein is a bad target or that targeting it with antibodies is never going to work.” The clinical trial team testing the antibody reported earlier this year in Nature Medicine that a small subgroup of its patients showed hints that prasinezumab slows the worsening of movement symptoms—although the group acknowledged that the finding emerged in a “posthoc analysis,” a secondary review unrelated to the trial’s hypothesis.

Manipulations in key experiment?

Five images in a 2005 paper in Neuron from Masliah and Prothena founder Dale Schenk appear to have been doctored in ways that could influence paper's findings. It is among several papers cited as key to the experimental drug prasinezumab that show apparent falsifications.

Still, “The discovery that key papers supporting this approach contained manipulated figures certainly muddies the waters,” Greenamyre says. He’s now hoping independent studies will determine whether “the rationale for clinical development remains on firm ground—or if it is now a little shaky.”

“We do not interpret these claims as specifically relevant to the current prasinezumab clinical program,” Prothena told Science in a brief statement responding to questions about the image anomalies related to the drug.

Swiss pharma giant Hoffmann-La Roche, which partnered with Prothena to develop prasinezumab in 2013, also supplied a statement in response to Science’s questions, saying it would continue clinical development of the drug. “The evidence supporting targeting alpha-synuclein aggregates as a mechanism of action in [Parkinson’s] is based on a wide range of sources,” it stated. In the interest of scientific integrity, Roche added, “We are working to further understand the details of this matter.”

Roche has agreed to pay Prothena up to $620 million if its drug candidate passes a series of performance goals. So far, Roche has paid $135 million.

Schenk and Masliah shared inventor credit in patents in the U.S. and Europe related to synuclein, amyloids, and related science, and they and their co-inventors assigned the rights to Prothena, UCSD, or both. Numerous other Prothena patents refer to suspect work cited in the dossier. Prothena and NIH did not respond to questions about whether Masliah has received or was promised royalties.

The dossier also questions some of Masliah’s earliest work on alpha-synuclein, raising further doubts about the foundations of Prothena’s drug. A seminal 2000 Masliah article in Science, for example, suggested alpha-synuclein might kill certain brain cells and speed the development of brain deposits called Lewy bodies that are hallmarks of Parkinson’s and are often seen in Alzheimer’s patients. But the paper contains an apparently doctored image and another image the dossier authors deemed questionable.

Other researchers have yet to validate aspects of that study, according to Ayton and neurologist Michael Okun of the University of Florida.

“A single nonreplicable finding is in itself not worrisome,” Okun says. But it raises greater concern in light of “convincing evidence of spliced and cloned images which appeared frequently in the decades following.” He calls it “deeply troubling” that FDA greenlighted human trials of prasinezumab based largely on suspect papers from Masliah’s lab.

People will, of course, be shocked, as I was. ... I was falling from a chair, basically.

Christian Haass

Ludwig Maximilians University Munich

FDA declined to comment on the prasinezumab findings challenged within the dossier. Holden Thorp, editor-in-chief of the Science family of journals, says the journal will “contact the authors [of the 2000 paper] to hear their response to these concerns. If any adjustments are required, we will certainly make them.” (Science’s News department is editorially independent of the journal.)

The new phase 2 trial of prasinezumab is examining whether it might slow the progression of certain movement difficulties caused by Parkinson’s, as the posthoc analysis suggested it might. Roche and Prothena expect to announce preliminary results later this year. The companies would likely decide in 2025 or 2026 on whether to move on to phase 3 trials—larger efficacy experiments needed for possible FDA approval.

The findings in the dossier cast a shadow on the other drug development efforts that rely on Masiah’s challenged work. And they raise questions about the roles and responsibilities of the many prominent scientists as well as more junior researchers who collaborated on some of his suspect experiments.

UCSD neuroscientist Edward Rockenstein, who worked under Masliah for years, co-authored 91 papers that contain questioned images, including 11 as first author. He died in 2022 at age 57. And neuroscientist Robert Rissman worked on 16 of the papers highlighted in the dossier, seven as senior author. He managed biomarkers and brain tissue samples for UCSD’s Alzheimer’s Disease Research Center prior to moving recently to USC, where he occupies a similar role and manages programs that try to move basic research into treatments for patients. Rissman did not reply to requests for comment. USC says it will conduct a confidential review of Rissman’s involvement with Masliah’s work.  

Haass questions whether Masliah’s closest collaborators could have remained unaware of the steady stream of apparent image manipulation, even if they were not personally culpable. “I mean, come on,” he says. “They must know.”

Other neuroscientists who spoke to Science urged caution in placing blame. “We should be careful … not to rush to judgment on the generation of researchers who may have been innocent members of this laboratory over the span of 20-plus years,” Okun says. “It is entirely possible that many were unaware of improprieties.”

In its statement today, NIH provided few details about the agency’s own investigation into Masliah’s work, including whether it had examined more than two of his publications. The agency says it has notified ORI of its findings and that the NIA deputy director, Amy Kelley, is also now acting head of the neuroscience division.

Given the NIH misconduct determination and the questions raised by the dossier about more than 100 other papers, many scientists—and perhaps congressional appropriators and the public—might question NIH’s vetting process for key roles and how Masliah retained stewardship of NIA’s billions of neuroscience dollars for so long. “For so important a job, you want somebody who is beyond reproach. You want somebody to be an exemplar of what you aspire to be,” Greenamyre says.

By the time NIA hired Masliah in 2016, image manipulation in scientific papers had already become a general concern. Prominent researchers increasingly faced accusations of image manipulation, plagiarism, or other misconduct—which often proved credible. But a former NIA official who would only speak if granted anonymity says he assumes the agency did not assess Masliah’s work for possible misconduct or data doctoring before he was hired.

Indeed, NIH told Science it does not routinely conduct such reviews, because of the difficulty of the process. “There is no evidence that such proactive screening would improve, or is necessary to improve, the research integrity environment at NIH,” the agency added.

Gandy disagrees. “It has to be part of the process now,” he says.

Greenamyre notes a concern about the episode also voiced by Haass and others who viewed the dossier: “I worry about it giving science a further black eye, just as the public’s confidence in science and scientists is sinking to new depths.” But, Greenamyre says, “In the interest of transparency and scientific integrity, this sad story has to come out.”

Questionable papers underpin other drugs

By Charles Piller

The possibility that neuroscientist Eliezer Masliah doctored images in scientific writings for decades is likely to provoke anxiety among multiple drug companies. The concerns documented by whistleblowers most directly challenge an experimental Parkinson’s therapy developed by Prothena (see main story). But 238 active patents concerning neurological conditions also cite suspect work noted in the dossier, according to data from Dimensions Analytics. And the corporate holders of those patents include dozens of firms at work on treatments.

The Austria-based biopharma company Ever Pharma relied heavily on Masliah’s questioned work in developing Cerebrolysin, a mixture of peptides—short chains of amino acids—derived from pig brains. Eight studies conducted at Masliah’s former lab at the University of California San Diego, funded in part by Ever Pharma, indicated the mixture suppresses brain inflammation, promotes growth of new brain cells, and has other benefits that could help dementia patients.

Small clinical trials of Cerebrolysin have suggested modest cognitive benefits in Alzheimer’s disease and vascular dementia, and Ever Pharma now distributes the drug in dozens of nations to treat dementia and stroke. But no large trials have demonstrated it helps dementia patients, and the Food and Drug Administration has not approved Cerebrolysin for use in the United States. And the eight lab studies used suspect images, according to the dossier.

For example, an article by Masliah and colleagues, in BMC Neuroscience in 2014, described the purported benefits of Cerebrolysin for symptoms of neurodegeneration in mice, including reducing mitochondrial damage. Another, published in Neurotoxicity Research in 2016, concerned mice infected with HIV. It republished what appears to be the same image of a mitochondrion.

A spokesperson for Springer Nature, publisher of Neurotoxicity Research, says the concerns will be examined, and responded to if warranted. Stefan Winter, who heads R&D for Ever Pharma’s neurological division, said in a written statement to Science that none of the challenged work in the dossier “played a crucial role in the clinical development of Cerebrolysin.” But, he added, “We take [the allegations] seriously. We will therefore review Prof. Masliah’s work based on the information you provided and refrain from using data from the mentioned publications until this matter is clarified.”

Another company, Neuropore Therapies, cites seven other papers in the Masliah dossier—all with apparently doctored images—as important to the company’s potential drugs for Parkinson’s. Masliah co-founded Neuropore in 2008 but no longer has any apparent affiliation. The most prominent drug candidate his work helped develop, minzasolmin, is in early clinical trials and targets the protein alpha-synuclein for Parkinson’s.

Masliah also provided imaging services for a 2023 paper in NPJ Parkinson’s Disease. The images, which purportedly show enhanced benefits in mice from minzasolmin, appear to be altered, according to the dossier. The concerns will be examined and responded to if warranted, says the journal’s publisher, Springer Nature. “We stand by our data related to clinical development programs,” said Mark Yung, executive chairman of Neuropore, in a brief written reply to detailed questions.

Minzasolmin has Big Pharma backing. In 2015, Neuropore licensed rights to develop and commercialize it and other molecules to the Brussels-based pharma company UCB for $63 million, plus possible future payments. In turn, the Swiss pharma titan Novartis paid UCB $150 million of a possible $1.5 billion for codevelopment rights for minzasolmin and another experimental drug.

“UCB will investigate the preclinical publication on minzasolmin” described in the Masliah dossier and will respond should “evidence of impropriety emerge,” said company spokesperson Laurent Schots in a written statement. But UCB knows of no “facts or circumstances that raise concerns on the quality, validity, and safety of the ongoing clinical development program for minzasolmin,” which is supported by evidence beyond the suspect Masliah work, Schots added.

Preliminary results for the drug’s efficacy from a clinical trial of 496 people in the U.S., Canada, and Europe could be announced later this year.