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Revision as of 15:54, 1 September 2022

Lindsay Burns
Personal information
BornTemplate:Birth-year-and-age
Big Timber, Montana, U.S.
Medal record
Women's rowing
Representing  United States
Olympic Games
Silver medal – second place 1996 Atlanta Lwt double sculls
World Rowing Championships
Gold medal – first place 1987 Copenhagen Lwt four
Silver medal – second place 1990 Tasmania Lwt double sculls
Silver medal – second place 1991 Vienna Lwt double sculls
Bronze medal – third place 1994 Indianapolis Lwt double sculls

Lindsay H. Burns is an American neuroscientist and rower who won a silver medal at the 1996 Summer Olympics.[1] She is a senior vice president of the pharmaceutical company Cassava Sciences[2] and married to its CEO Remi Barbier.

As of July 2022, Cassava Sciences and papers published by Burns are under investigation; Cassava denies any wrongdoing.[3][4][5][6][7]

Personal life

Burns was born on 6 January 1965[8] and raised in Big Timber, Montana.[9] She graduated from Harvard University in 1987.[9] In 1991, she obtained a PhD in neuroscience from University of Cambridge[9] on a thesis titled Functional interactions of limbic afferents to the striatum and mesolimbic dopamine in reward-related processes,[10] which was supervised by Barry Everitt and Trevor Robbins.[11][12]

Burns worked as a research fellow in psychobiology at McLean Hospital in Belmont, Massachusetts.[9] She joined Cassava Sciences in 2002 and became senior vice president of neuroscience in 2021.[13]

Burns is married to Remi Barbier, the CEO and founder of Cassava Sciences.[14][15][16]

Rowing career

Burns started competitive rowing soon after entering Harvard.[9] In 1987, she rowed in the Radcliffe varsity crew and won the Eastern Association of Women's Rowing Colleges (EAWRC) championship that gave her the Ivy title and the EAWRC League title.[14] She was included the US rowing team from 1987 and from 1990-1996. Having competed at six World Rowing Championships, she had won four medals such as gold in the four in 1987, silvers in the double in 1990 and 1991, and a bronze in the double in 1994, all in the lightweight category. She also 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.[17] 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.[14] In 2016, she was inducted into the National Rowing Foundation Hall of Fame.[18]

Scientific works

Burns' 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.[19] She continued her PhD research on the role of dopamine and the limbic system.[11][12][10][20][21] 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.[22] Further research indicated possible use in humans.[23] 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.[24]

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.[25][26][27][28]

Since 2006, Burns has collaborated with Hoau-Yan Wang at the City University of New York,[29] who had been investigating Alzheimer's disease. Previously identifying filamin A (FLNA) for its role in regulating opioid receptor signaling, Burns and Wang then identified FLNA as a critical protein in enabling Abeta42's signaling through the alpha 7 nicotinic acetylcholine receptor to induce Alzheimer's disease pathology.[30][31][32]

FLNA, simufilam and Alzheimer's disease

In 2008, Burns, Wang and Maya Frankfurt published in PLOS One a finding that the opioid antagonists naloxone and naltrexone bind with ultra-high affinity to FLNA to prevent mu opioid receptor excitatory signaling.[33] Burns and Wang identified the binding site on FLNA and the activation of CREB by opioid receptor - Gs coupling in the same journal the next year.[34] 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.[35]

In 2012, they published in The Journal of Neuroscience a novel compound PTI-125 that binds to FLNA similarly to naloxone and naltrexone.[36] With PTI-125, they stated that FLNA aberrantly links to the alpha 7 nicotinic receptor, enabling signaling of Abeta42 to hyperphosphorylate tau.[31][36]

In 2017, they reported in Neurobiology of Aging 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.[37][38] The United States Adopted Names (USAN) gave the drug name for PTI-125 as simufilam in 2020;[39] as of 2022, it is in Phase III clinical trials.

Research controversies

Further information: Cassava Sciences § Allegations of research fraud

As of July 2022, Cassava Sciences and papers published by Burns and Wang are under investigation; Cassava denies any wrongdoing.[3][4][5]

References

  1. ^ a b c "Biography: Lindsay Burns". Olympics. International Olympic Committee. Retrieved May 2, 2022.
  2. ^ Keown, Alex (April 19, 2022). "Cassava Faces Renewed Speculation Over Experimental Alzheimer's Drug". BioSpace. Retrieved May 9, 2022.
  3. ^ a b Taylor, Marisa; Spector, Mike (July 27, 2022). "Exclusive: Cassava Sciences faces U.S. criminal probe tied to Alzheimer's drug, sources say". Reuters. Retrieved July 31, 2022.
  4. ^ a b "Cassava Sciences Responds to Media Reports" (Press release). Cassava Sciences. July 27, 2022. Retrieved August 16, 2022.
  5. ^ a b Michaels, Dave; Walker, Joseph (November 17, 2021). "SEC Investigating Cassava Sciences, Developer of Experimental Alzheimer's Drug". Wall Street Journal. ISSN 0099-9660. Retrieved April 29, 2022.
  6. ^ Mandavilli, Apoorva (April 18, 2022). "Scientists Question Data Behind an Experimental Alzheimer's Drug". The New York Times. ISSN 0362-4331. Retrieved April 28, 2022.
  7. ^ "The Cassava Sciences saga: Short sellers, 'gaming' the FDA, and the damaging ripple effects".
  8. ^ "Lindsay Burns". World Rowing.
  9. ^ a b c d e "Harvard at the Olympics". Harvard Magazine. Retrieved May 3, 2022.
  10. ^ a b Burns, Lindsay H. (1991). Functional interactions of limbic afferents to the striatum and mesolimbic dopamine in reward-related processes (Ph.D. thesis). University of Cambridge. OCLC 556753196.
  11. ^ a b Burns, L; Robbins, T; Everitt, B (1993). "Differential effects of excitotoxic lesions of the basolateral amygdala, ventral subiculum and medial prefrontal cortex on responding with conditioned reinforcement and locomotor activity potentiated by intra-accumbens infusions ofd-amphetamine". Behavioural Brain Research. 55 (2): 167–183. doi:10.1016/0166-4328(93)90113-5. PMID 8357526. S2CID 4032314.
  12. ^ a b Burns, Lindsay H.; Everitt, Barry J.; Kelley, Ann E.; Robbins, Trevor W. (1994). "Glutamate-dopamine interactions in the ventral striatum: role in locomotor activity and responding with conditioned reinforcement". Psychopharmacology. 115 (4): 516–528. doi:10.1007/BF02245576. PMID 7871097. S2CID 28351013.
  13. ^ "Lindsay H Burns, Cassava Sciences Inc: Profile and Biography". Bloomberg.com. Retrieved May 3, 2022.
  14. ^ a b c "Lindsay Burns Barbier '87". www.harvardvarsityclub.org. Retrieved May 2, 2022.
  15. ^ Keefe, Patrick Radden (January 15, 2022). "Jordan Thomas's Army of Whistle-Blowers". The New Yorker. Archived from the original on July 22, 2022. Retrieved April 29, 2022.
  16. ^ Feuerstein, Adam (April 5, 2022). "Troubles mount for Cassava Sciences, as patient enrollment lags for Alzheimer's drug studies". STAT. Retrieved April 30, 2022.
  17. ^ "Rowing News". July 16–29, 1995.
  18. ^ "The National Rowing Foundation Announces the 2016 Inductees to the National Rowing Hall of Fame". January 26, 2016.
  19. ^ Burns, Lindsay H.; Kelley, Ann E. (1988). "Neurokinin-α injected into the ventral tegmental area elicits a dopamine-dependent behavioral activation in the rat". Pharmacology Biochemistry and Behavior. 31 (2): 255–263. doi:10.1016/0091-3057(88)90343-7. PMID 2469085. S2CID 20941335.
  20. ^ Burns, Lindsay H.; Annett, Lucy; Kelly, Ann E.; Everitt, Barry J.; Robbins, Trevor W. (1996). "Effects of lesions to amygdala, ventral subiculum, medial prefrontal cortex, and nucleus accumbens on the reaction to novelty: Implications for limbic—striatal interactions". Behavioral Neuroscience. 110 (1): 60–73. doi:10.1037/0735-7044.110.1.60. ISSN 1939-0084. PMID 8652073.
  21. ^ Parkinson, John A.; Olmstead, Mary C.; Burns, Lindsay H.; Robbins, Trevor W.; Everitt, Barry J. (1999). "Dissociation in Effects of Lesions of the Nucleus Accumbens Core and Shell on Appetitive Pavlovian Approach Behavior and the Potentiation of Conditioned Reinforcement and Locomotor Activity byd-Amphetamine". Journal of Neuroscience. 19 (6): 2401–2411. doi:10.1523/JNEUROSCI.19-06-02401.1999. PMC 6782569. PMID 10066290.
  22. ^ Isacson, Ole; Deacon, Terrence W.; Pakzaban, Peyman; Galpern, Wendy R.; Dinsmore, Jonathan; Burns, Lindsay H. (1995). "Transplanted xenogeneic neural cells in neurodegenerative disease models exhibit remarkable axonal target specificity and distinct growth patterns of glial and axonal fibres". Nature Medicine. 1 (11): 1189–1194. doi:10.1038/nm1195-1189. PMID 7584993. S2CID 7344970.
  23. ^ Galpern, Wendy R.; Burns, Lindsay H.; Deacon, Terrence W.; Dinsmore, Jonathan; Isacson, Ole (1996). "Xenotransplantation of Porcine Fetal Ventral Mesencephalon in a Rat Model of Parkinson's Disease: Functional Recovery and Graft Morphology". Experimental Neurology. 140 (1): 1–13. doi:10.1006/exnr.1996.0109. PMID 8682173. S2CID 23945411.
  24. ^ Burns, Lindsay H.; Jin, Zhen; Bowersox, S.Scott (1999). "The neuroprotective effects of intrathecal administration of the selective N-type calcium channel blocker ziconotide in a rat model of spinal ischemia". Journal of Vascular Surgery. 30 (2): 334–343. doi:10.1016/S0741-5214(99)70145-X. PMID 10436454.
  25. ^ Chindalore, Vishala L.; Craven, Richard A.; Yu, K. Peony; Butera, Peter G.; Burns, Lindsay H.; Friedmann, Nadav (2005). "Adding Ultralow-Dose Naltrexone to Oxycodone Enhances and Prolongs Analgesia: A Randomized, Controlled Trial of Oxytrex". The Journal of Pain. 6 (6): 392–399. doi:10.1016/j.jpain.2005.01.356. PMID 15943961.
  26. ^ Olmstead, Mary C.; Burns, Lindsay H. (2005). "Ultra-low-dose naltrexone suppresses rewarding effects of opiates and aversive effects of opiate withdrawal in rats". Psychopharmacology. 181 (3): 576–581. doi:10.1007/s00213-005-0022-7. PMID 16010543. S2CID 13270740.
  27. ^ Leri, Francesco; Burns, Lindsay H. (2005). "Ultra-low-dose naltrexone reduces the rewarding potency of oxycodone and relapse vulnerability in rats". Pharmacology Biochemistry and Behavior. 82 (2): 252–262. doi:10.1016/j.pbb.2005.08.008. PMID 16182352. S2CID 25513761.
  28. ^ Burns, Lindsay H.; Vanderah, Todd W.; Wang, Hoau-Yan (2009), Dean, Reginald L.; Bilsky, Edward J.; Negus, S. Stevens (eds.), "Ultra-Low-Dose Opioid Antagonists Enhance Opioid Analgesia and Reduce Tolerance", Opiate Receptors and Antagonists, Totowa, NJ: Humana Press, pp. 3–17, doi:10.1007/978-1-59745-197-0_1, ISBN 978-1-58829-881-2, retrieved May 3, 2022
  29. ^ Wang, Hoau-Yan; Burns, Lindsay H. (2006). "Gβγ that interacts with adenylyl cyclase in opioid tolerance originates from a Gs protein". Journal of Neurobiology. 66 (12): 1302–1310. doi:10.1002/neu.20286. PMID 16967511.
  30. ^ Wang, Hoau-Yan; Bakshi, Kalindi; Frankfurt, Maya; Stucky, Andres; Goberdhan, Marissa; Shah, Sanket M.; Burns, Lindsay H. (2012). "Reducing Amyloid-Related Alzheimer's Disease Pathogenesis by a Small Molecule Targeting Filamin A". J Neurosci. 32 (29): 9773–9784. doi:10.1523/JNEUROSCI.0354-12.2012. PMC 6621293. PMID 22815492. S2CID 9933756.
  31. ^ a b Burns, Lindsay H.; Wang, Hoau-Yan (2017). "Altered filamin A enables amyloid beta-induced tau hyperphosphorylation and neuroinflammation in Alzheimer's disease". Neuroimmunology and Neuroinflammation. 4 (12): 263–271. doi:10.20517/2347-8659.2017.50. PMC 8294116. PMID 34295950.
  32. ^ Wang, Hoau‐Yan; Pei, Zhe; Xu, Qiang; Brunelle, Lynn A; Burns, Lindsay H.; Thornton, George Ben (2021). "SavaDx, a novel plasma biomarker to detect Alzheimer's disease, confirms mechanism of action of simufilam". Alzheimer's & Dementia. 17 (S5): online. doi:10.1002/alz.054385. S2CID 245570217.
  33. ^ Wang, Hoau-Yan; Frankfurt, Maya; Burns, Lindsay H. (February 6, 2008). "High-affinity naloxone binding to filamin a prevents mu opioid receptor-Gs coupling underlying opioid tolerance and dependence". PLOS ONE. 3 (2): e1554. Bibcode:2008PLoSO...3.1554W. doi:10.1371/journal.pone.0001554. PMC 2212716. PMID 18253501.
  34. ^ Wang, Hoau-Yan; Burns, Lindsay H. (2009). "Naloxone's pentapeptide binding site on filamin A blocks Mu opioid receptor-Gs coupling and CREB activation of acute morphine". PLOS ONE. 4 (1): e4282. Bibcode:2009PLoSO...4.4282W. doi:10.1371/journal.pone.0004282. ISSN 1932-6203. PMC 2628740. PMID 19172190.
  35. ^ Burns, Lindsay H.; Wang, Hoau-Yan (2010). "PTI-609: A Novel Analgesic that Binds Filamin A to Control Opioid Signaling". Recent Patents on CNS Drug Discovery. 5 (3): 210–220. doi:10.2174/157488910793362386. PMID 20726836.
  36. ^ a b Wang, H.-Y.; Bakshi, K.; Frankfurt, M.; Stucky, A.; Goberdhan, M.; Shah, S. M.; Burns, L. H. (2012). "Reducing Amyloid-Related Alzheimer's Disease Pathogenesis by a Small Molecule Targeting Filamin A". Journal of Neuroscience. 32 (29): 9773–9784. doi:10.1523/JNEUROSCI.0354-12.2012. PMC 6621293. PMID 22815492.
  37. ^ Wang, Hoau-Yan; Lee, Kuo-Chieh; Pei, Zhe; Khan, Amber; Bakshi, Kalindi; Burns, Lindsay H. (2017). "PTI-125 binds and reverses an altered conformation of filamin A to reduce Alzheimer's disease pathogenesis". Neurobiology of Aging. 55: 99–114. doi:10.1016/j.neurobiolaging.2017.03.016. PMID 28438486. S2CID 207163555.
  38. ^ Toniolo, Sofia; Sen, Arjune; Husain, Masud (2020). "Modulation of Brain Hyperexcitability: Potential New Therapeutic Approaches in Alzheimer's Disease". International Journal of Molecular Sciences. 21 (23): 9318. doi:10.3390/ijms21239318. PMC 7730926. PMID 33297460.
  39. ^ "Cassava Sciences Announces Lead Drug Candidate PTI-125 Is Assigned the Chemical Drug Name 'sumifilam' by USAN". Global Newswire (Press release). Cassava Sciences. August 24, 2020. Retrieved May 3, 2022.

External links

Retrieved from "https://en.wikipedia.org/w/index.php?title=Lindsay_Burns&oldid=1107925112"