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Born | 1965 (age 58–59) Big Timber, Montana, U.S. | |||||||||||||||||||||||||||||
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Lindsay H. Burns (born 1965) is an American neuroscientist and rower who won a silver medal at the 1996 Summer Olympics. [1] She was a senior vice president of the pharmaceutical company Cassava Sciences [2] until July 2024 and married to its CEO Remi Barbier.
As of July 2022, Cassava Sciences and papers co-authored by Burns were under investigation; [3] [4] co-author Hoau-Yan Wang was indicted for fraud in 2024 and Cassava denies any wrongdoing. [5] Burns and her husband, Remi Barbier (president and chief executive officer of Cassava) [6] [7] [8] [9] abruptly resigned in 2024 following Wang's indictment. [10] [11]
Burns was born in 1965 [12] and raised in Big Timber, Montana. [13] She graduated from Harvard University in 1987. [13] In 1991, she obtained a PhD in neuroscience from University of Cambridge [13] on a thesis titled Functional interactions of limbic afferents to the striatum and mesolimbic dopamine in reward-related processes, [14] which was supervised by Barry Everitt and Trevor Robbins. [15] [16]
Burns worked as a research fellow in psychobiology at McLean Hospital in Belmont, Massachusetts. [13] She joined Cassava Sciences in 2002 and became senior vice president of neuroscience in 2021. [17]
Burns is married to Remi Barbier, the former CEO [10] [11] and founder of Cassava Sciences. [9] [7] [18]
Burns started competitive rowing soon after entering Harvard. [13] In 1987, she rowed in the Radcliffe varsity crew and won the Eastern Association of Women's Rowing Colleges (EAWRC) championship that awarded her the Ivy title and the EAWRC League title. [9] She was part of the US rowing team from 1987 and from 1990–1996. Competing in the lightweight category at six World Rowing Championships, she won four medals: gold at the 1987; silvers in the double in 1990 and 1991; and bronze in the double in 1994. She won a silver medal at the 1995 Pan American Games competing in the quad sculls (heavyweight) category [1] and she won the European Rowing Championships at Lucerne in 1995 with Teresa Bell. [19] She was an alternate rower at the 1992 Summer Olympics in Barcelona, Spain.[ citation needed ]
She teamed up again with Teresa Bell at the 1996 Summer Olympics in Atlanta, United States, and won a silver medal in the Lightweight Double Sculls. [1] In 2006, she was inducted into the Harvard Sports Hall of Fame. [9] In 2016, she was inducted into the National Rowing Foundation Hall of Fame. [20]
This article may rely excessively on sources too closely associated with the subject , potentially preventing the article from being verifiable and neutral.(August 2022) |
Burns's first research was on the effect of neurokinin A on brain functions in rats. Her first paper in 1988, written with Ann E. Kelley, reported that neurokinin A in the ventral tegmental area modifies dopamine circuits to induce behavioral changes. [21] She continued her PhD research on the role of dopamine and the limbic system. [15] [16] [14] [22] [23] During her post-doc at McLean Hospital, she focused on neurodegenerative diseases, specifically, transplantation of pig neural cells into rat brain as a possible treatment of Parkinson's or Huntington's disease. [24] Further research indicated possible use in humans. [25] While working for a biotech company later acquired by Elan Pharmaceuticals, she published the effects of ziconotide in a rat model of spinal cord ischemia. [26]
In 2005, she published a series of papers on Oxytrex and related research with ultra-low doses of certain (opioid antagonists) to enhance analgesia and prevent opioid-induced hyperalgesia, opioid tolerance and substance dependence. [27] [28] [29] [30]
Since 2006, Burns collaborated with Hoau-Yan Wang at the City University of New York, [31] who had been investigating Alzheimer's disease. Burns and Wang wrote that FLNA was a critical protein in enabling Abeta42's signaling through the alpha 7 nicotinic acetylcholine receptor to induce Alzheimer's disease pathology (the publication has an expression of concern). [32] [33] [34]
In 2008, Burns, Wang and Maya Frankfurt published in PLOS One a (later retracted) finding that the opioid antagonists naloxone and naltrexone bind with ultra-high affinity to FLNA to prevent mu opioid receptor excitatory signaling. [35] Burns and Wang published (now retracted) the binding site on FLNA and the activation of CREB by opioid receptor – Gs coupling in the same journal the next year. [36] FLNA is a cytoplasmic protein that maintains normal cell shape and division. In 2010, Burns and Wang announced a novel analgesic" which they named PTI-609 (PTI for Pain Therapeutics, Inc., the former name of Cassava Sciences) and stated that the molecule binds to FLNA as well as activating mu opioid receptors. [37]
In 2012, they published in The Journal of Neuroscience (now with an expression of concern) a novel compound PTI-125 that binds to FLNA similarly to naloxone and naltrexone. [38] With PTI-125, they stated that FLNA aberrantly links to the alpha 7 nicotinic receptor, enabling signaling of Abeta42 to hyperphosphorylate tau. [33] [38]
In 2017, they stated in Neurobiology of Aging (now with an expression of concern) that the FLNA in Alzheimer's disease transgenic mice and human postmortem brain tissue has an altered conformation (based on a shift in isoelectric focusing) and that PTI-125 binding to altered FLNA restores its normal shape, thereby reducing tau hyperphosphorylation, amyloid deposits and tau-containing lesions in the brains of the mice. [39] [40] The United States Adopted Names (USAN) gave the drug name for PTI-125 as simufilam in 2020; [41] as of 2022, it is in Phase III clinical trials.
In June 2024, Wang was indicted by the United States Department of Justice (DOJ) for fraud and charged with falsifying data on $16 million in grant applications to the NIH related to the Alzheimer's drug in development, simufilam. [5] [42] [43] [44] As of July 2022, Cassava Sciences and papers published by Burns and Wang were under investigation by the DOJ; Cassava denies any wrongdoing. [45] [46] [47] The U.S. Securities and Exchange Commission (SEC), the U.S. National Institutes of Health (NIH), and City University of New York (CUNY) were also investigating allegations of manipulated data. [47]
In October 2023, CUNY reported that they could obtain none of Wang's original data. [48] [49] According to The Wall Street Journal, the CUNY report stated that Burns shared with Wang some responsibility "for errors and misconduct". [49]
Opioid use disorder (OUD) is a substance use disorder characterized by cravings for opioids, continued use despite physical and/or psychological deterioration, increased tolerance with use, and withdrawal symptoms after discontinuing opioids. Opioid withdrawal symptoms include nausea, muscle aches, diarrhea, trouble sleeping, agitation, and a low mood. Addiction and dependence are important components of opioid use disorder.
Naltrexone, sold under the brand name Revia among others, is a medication primarily used to manage alcohol use or opioid use disorder by reducing cravings and feelings of euphoria associated with substance use disorder. It has also been found effective in the treatment of other addictions and may be used for them off-label. An opioid-dependent person should not receive naltrexone before detoxification. It is taken by mouth or by injection into a muscle. Effects begin within 30 minutes, though a decreased desire for opioids may take a few weeks to occur. Side effects may include trouble sleeping, anxiety, nausea, and headaches. In those still on opioids, opioid withdrawal may occur. Use is not recommended in people with liver failure. It is unclear if use is safe during pregnancy. Naltrexone is an opioid antagonist and works by blocking the effects of opioids, including both opioid drugs as well as opioids naturally produced in the brain.
Neuropharmacology is the study of how drugs affect function in the nervous system, and the neural mechanisms through which they influence behavior. There are two main branches of neuropharmacology: behavioral and molecular. Behavioral neuropharmacology focuses on the study of how drugs affect human behavior (neuropsychopharmacology), including the study of how drug dependence and addiction affect the human brain. Molecular neuropharmacology involves the study of neurons and their neurochemical interactions, with the overall goal of developing drugs that have beneficial effects on neurological function. Both of these fields are closely connected, since both are concerned with the interactions of neurotransmitters, neuropeptides, neurohormones, neuromodulators, enzymes, second messengers, co-transporters, ion channels, and receptor proteins in the central and peripheral nervous systems. Studying these interactions, researchers are developing drugs to treat many different neurological disorders, including pain, neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease, psychological disorders, addiction, and many others.
An opioid antagonist, or opioid receptor antagonist, is a receptor antagonist that acts on one or more of the opioid receptors.
The κ-opioid receptor or kappa opioid receptor, abbreviated KOR or KOP for its ligand ketazocine, is a G protein-coupled receptor that in humans is encoded by the OPRK1 gene. The KOR is coupled to the G protein Gi/G0 and is one of four related receptors that bind opioid-like compounds in the brain and are responsible for mediating the effects of these compounds. These effects include altering nociception, consciousness, motor control, and mood. Dysregulation of this receptor system has been implicated in alcohol and drug addiction.
Low-dose naltrexone (LDN) refers to daily naltrexone dosages that are roughly one-tenth of the standard opioid addiction treatment dosage. Most published research suggests a daily dosage of 4.5 mg, but this can vary by a few milligrams. Low-dose naltrexone has been studied for the treatment of multiple chronic pain disorders including fibromyalgia, multiple sclerosis, Crohn’s disease, and complex regional pain syndrome.
Nalmefene is a medication that is used in the treatment of opioid overdose and alcohol dependence. Nalmefene belongs to the class of opioid antagonists and can be taken by mouth, administered by injection, or delivered through nasal administration.
The sigma-1 receptor (σ1R), one of two sigma receptor subtypes, is a chaperone protein at the endoplasmic reticulum (ER) that modulates calcium signaling through the IP3 receptor. In humans, the σ1 receptor is encoded by the SIGMAR1 gene.
NMDA receptor antagonists are a class of drugs that work to antagonize, or inhibit the action of, the N-Methyl-D-aspartate receptor (NMDAR). They are commonly used as anesthetics for humans and animals; the state of anesthesia they induce is referred to as dissociative anesthesia.
Toll-like receptor 4 (TLR4), also designated as CD284, is a key activator of the innate immune response and plays a central role in the fight against bacterial infections. TLR4 is a transmembrane protein of approximately 95 kDa that is encoded by the TLR4 gene.
Nalfurafine is an antipruritic that is marketed in Japan for the treatment of uremic pruritus in individuals with chronic kidney disease undergoing hemodialysis. It activates the κ-opioid receptor (KOR) and is potent, selective, and centrally active. It was the first selective KOR agonist approved for clinical use. It has also been dubiously referred to as the "first non-narcotic opioid drug" in history.
Dopamine receptor D1, also known as DRD1. It is one of the two types of D1-like receptor family — receptors D1 and D5. It is a protein that in humans is encoded by the DRD1 gene.
Filamin A, alpha (FLNA) is a protein that in humans is encoded by the FLNA gene.
Dopamine receptor D3 is a protein that in humans is encoded by the DRD3 gene.
Homotaurine is a natural sulfonic acid found in seaweed. It is analogous to taurine, but with an extra carbon in its chain. It has GABAergic activity, apparently by mimicking GABA, which it resembles.
Naltrexone/bupropion, sold under the brand name Contrave among others, is a fixed-dose combination medication for the management of chronic obesity in adults in combination with a reduced-calorie diet and increased physical activity. It contains naltrexone, an opioid antagonist, and bupropion, an aminoketone atypical antidepressant. It is taken by mouth. Both medications have individually shown some evidence of effectiveness in weight loss, and the combination has been shown to have some synergistic effects on weight.
Brexpiprazole, sold under the brand name Rexulti among others, is an atypical antipsychotic medication used for the treatment of major depressive disorder, schizophrenia, and agitation associated with dementia due to Alzheimer's disease.
6β-Naltrexol, or 6β-hydroxynaltrexone, is a peripherally-selective opioid receptor antagonist related to naltrexone. It is a major active metabolite of naltrexone formed by hepatic dihydrodiol dehydrogenase enzymes. With naltrexone therapy, 6β-naltrexol is present at approximately 10- to 30-fold higher concentrations than naltrexone at steady state due to extensive first-pass metabolism of naltrexone into 6β-naltrexol. In addition to being an active metabolite of naltrexone, 6β-naltrexol was itself studied for the treatment of opioid-induced constipation. It was found to be effective and well-tolerated, and did not precipitate opioid withdrawal symptoms or interfere with opioid pain relief, but development was not further pursued.
Simufilam (PTI-125) is an experimental medication for the treatment of Alzheimer's disease. It is being developed by the American pharmaceutical firm Cassava Sciences. The drug is in phase III clinical trials as of October 2023. There are two phase III clinical studies: RETHINK-ALZ, a 52-week trial, is set to complete in 2024, and REFOCUS-ALZ, spanning 76 weeks, is projected to finish in 2025.
Cassava Sciences is an American pharmaceutical company based in Austin, Texas. The company was founded in 1998 by Remi Barbier as Pain Therapeutics, Inc., changing its name in 2019.