Donald F. Weaver

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Donald F. Weaver is a Canadian chemist and neurologist based at the Krembil Research Institute, University Health Network, University of Toronto, Canada. He is Senior Scientist of the Krembil Research Institute and Professor of Neurology, Chemistry, and Pharmaceutical Sciences, University of Toronto. [1] [2] He is a Fellow of the Royal College of Physicians (Canada), Fellow of the Chemical Institute of Canada, and Fellow of the Canadian Academy of Health Sciences. [3]

Contents

Weaver specializes in memory and seizure disorders; his clinical practice included research in both basic and translational science as well as the presidency of Epilepsy Canada, the directorship of the Krembil Research Institute & the Krembil Brain Institute as well as appointments as Tier 1 Canada Research Chairs. [4] He is known for his research into the biomolecular mechanisms of neurodegenerative diseases with a current focus on innate immunity and re-conceptualizing Alzheimer’s disease (AD) as an disorder of autoimmunity. [5] [6] His contributions also include the design and synthesis of new chemical entities as putative therapeutics for AD and related dementias. [7] [8] [9]

He has also co-founded Neurochem Inc. and Treventis Corp., both focused on developing drugs for Alzheimer’s disease (AD). Neurochem proceeded to an initial public offering (IPO) on the TSX and NASDAQ and advanced two compounds to Phase III human trials. Treventis, similarly arose from Weaver’s academic laboratory, and has developed small molecule therapeutics targeting tau in AD and has established collaboration with Takeda Inc. for their continued development.[ citation needed ]

Biography

Weaver was born in North Bay, Ontario. He completed his MD at Queen’s University, followed by an internal medicine internship at the Hôtel-Dieu and Kingston General Hospitals. He next completed clinical residency training in Neurology at the Queen Elizabeth II Health Sciences Centre, Dalhousie University; where he also undertook additional training in behavioural neurology.  He returned to Queen’s University obtaining a Ph.D. in theoretical and organic chemistry, defending a dissertation on the applications of quantum mechanics and synthetic organic chemistry to neurologic drug design.[ citation needed ]

In his first academic appointment, he taught chemistry and neurology at Queen’s University. While at Queen’s, he established the first memory disorders clinic at that institution and was Professor and Head of the Division of Neurology from 1998 to 2001. He subsequently moved to Dalhousie University as a Tier 1 Canada Research Chair in Neurodegenerative Diseases. [10] While there he also became the inaugural Sobey Endowed Chair in Curative Approaches to Alzheimer’s Disease. [11] He next relocated to Toronto as a Tier 1 Canada Research Chair in Protein Misfolding and as the inaugural Director of the Krembil Research Institute. [4]

He has been studying Alzheimer’s disease using theoretical/computational chemistry methods for more than 30 years. He was the computational chemist whose in silico screen identified analogues of taurine as potential disease modifying agents for AD; this led to the development of tramiprosate, which reached Phase III human trials for AD, and to eprodisate for the treatment of renal amyloidosis. [12] [13]

Weaver's peer-reviewed publications number over 400 - spanning clinical and basic science (theoretical and synthetic chemistry).  He has 48 issued patents.  He has also published poetry and short stories in the area of dementia. [14] [15] [16] [17]

Awards and honours

Related Research Articles

<span class="mw-page-title-main">Dementia</span> Long-term brain disorders causing impaired memory, thinking and behavior

Dementia is the general name for a decline in cognitive abilities that impacts a person's ability to perform everyday activities. This typically involves problems with memory, thinking, and behavior. Aside from memory impairment and a disruption in thought patterns, the most common symptoms include emotional problems, difficulties with language, and decreased motivation. The symptoms may be described as occurring in a continuum over several stages. Dementia ultimately has a significant effect on the individual, caregivers, and on social relationships in general. A diagnosis of dementia requires the observation of a change from a person's usual mental functioning and a greater cognitive decline than what is caused by normal aging.

<span class="mw-page-title-main">Amyloid plaques</span> Extracellular deposits of the amyloid beta protein

Amyloid plaques are extracellular deposits of the amyloid beta (Aβ) protein mainly in the grey matter of the brain. Degenerative neuronal elements and an abundance of microglia and astrocytes can be associated with amyloid plaques. Some plaques occur in the brain as a result of aging, but large numbers of plaques and neurofibrillary tangles are characteristic features of Alzheimer's disease. Abnormal neurites in amyloid plaques are tortuous, often swollen axons and dendrites. The neurites contain a variety of organelles and cellular debris, and many of them include characteristic paired helical filaments, the ultrastructural component of neurofibrillary tangles. The plaques are highly variable in shape and size; in tissue sections immunostained for Aβ, they comprise a log-normal size distribution curve with an average plaque area of 400-450 square micrometers (µm²). The smallest plaques, which often consist of diffuse deposits of Aβ, are particularly numerous. The apparent size of plaques is influenced by the type of stain used to detect them, and by the plane through which they are sectioned for analysis under the microscope. Plaques form when Aβ misfolds and aggregates into oligomers and longer polymers, the latter of which are characteristic of amyloid. Misfolded and aggregated Aβ is thought to be neurotoxic, especially in its oligomeric state.

Semantic dementia (SD), also known as semantic variant primary progressive aphasia (svPPA), is a progressive neurodegenerative disorder characterized by loss of semantic memory in both the verbal and non-verbal domains. However, the most common presenting symptoms are in the verbal domain. Semantic dementia is a disorder of semantic memory that causes patients to lose the ability to match words or images to their meanings. However, it is fairly rare for patients with semantic dementia to develop category specific impairments, though there have been documented cases of it occurring. Typically, a more generalized semantic impairment results from dimmed semantic representations in the brain.

<span class="mw-page-title-main">Tauopathy</span> Medical condition

Tauopathy belongs to a class of neurodegenerative diseases involving the aggregation of tau protein into neurofibrillary or gliofibrillary tangles in the human brain. Tangles are formed by hyperphosphorylation of the microtubule protein known as tau, causing the protein to dissociate from microtubules and form insoluble aggregates. The mechanism of tangle formation is not well understood, and whether tangles are a primary cause of Alzheimer's disease or play a peripheral role is unknown.

<span class="mw-page-title-main">Neurodegenerative disease</span> Central nervous system disease

A neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell death. Neurodegenerative diseases include amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, Alzheimer's disease, Huntington's disease, multiple system atrophy, tauopathies, and prion diseases. Neurodegeneration can be found in the brain at many different levels of neuronal circuitry, ranging from molecular to systemic. Because there is no known way to reverse the progressive degeneration of neurons, these diseases are considered to be incurable; however research has shown that the two major contributing factors to neurodegeneration are oxidative stress and inflammation. Biomedical research has revealed many similarities between these diseases at the subcellular level, including atypical protein assemblies and induced cell death. These similarities suggest that therapeutic advances against one neurodegenerative disease might ameliorate other diseases as well.

<span class="mw-page-title-main">Proteinopathy</span> Medical condition

In medicine, proteinopathy, or proteopathy, protein conformational disorder, or protein misfolding disease, is a class of diseases in which certain proteins become structurally abnormal, and thereby disrupt the function of cells, tissues and organs of the body. Often the proteins fail to fold into their normal configuration; in this misfolded state, the proteins can become toxic in some way or they can lose their normal function. The proteinopathies include such diseases as Creutzfeldt–Jakob disease and other prion diseases, Alzheimer's disease, Parkinson's disease, amyloidosis, multiple system atrophy, and a wide range of other disorders. The term proteopathy was first proposed in 2000 by Lary Walker and Harry LeVine.

Mild cognitive impairment (MCI) is a neurocognitive disorder which involves cognitive impairments beyond those expected based on an individual's age and education but which are not significant enough to interfere with instrumental activities of daily living. MCI may occur as a transitional stage between normal aging and dementia, especially Alzheimer's disease. It includes both memory and non-memory impairments. The cause of the disorder remains unclear, as well as both its prevention and treatment, with some 50 percent of people diagnosed with it going on to develop Alzheimer's disease within five years. The diagnosis can also serve as an early indicator for other types of dementia, although MCI may remain stable or even remit.

The prevention of dementia involves reducing the number of risk factors for the development of dementia, and is a global health priority needing a global response. Initiatives include the establishment of the International Research Network on Dementia Prevention (IRNDP) which aims to link researchers in this field globally, and the establishment of the Global Dementia Observatory a web-based data knowledge and exchange platform, which will collate and disseminate key dementia data from members states. Although there is no cure for dementia, it is well established that modifiable risk factors influence both the likelihood of developing dementia and the age at which it is developed. Dementia can be prevented by reducing the risk factors for vascular disease such as diabetes, high blood pressure, obesity, smoking, physical inactivity and depression. A study concluded that more than a third of dementia cases are theoretically preventable. Among older adults both an unfavorable lifestyle and high genetic risk are independently associated with higher dementia risk. A favorable lifestyle is associated with a lower dementia risk, regardless of genetic risk. In 2020, a study identified 12 modifiable lifestyle factors, and the early treatment of acquired hearing loss was estimated as the most significant of these factors, potentially preventing up to 9% of dementia cases.

<span class="mw-page-title-main">Gregory Petsko</span> American biochemist and academic

Gregory A. Petsko is an American biochemist and member of the National Academy of Sciences, the National Academy of Medicine, the American Academy of Arts and Sciences, and the American Philosophical Society. He is currently Professor of Neurology at the Ann Romney Center for Neurologic Diseases at Harvard Medical School and Brigham and Women's Hospital. He formerly had an endowed professorship in Neurology and Neuroscience at Weill Cornell Medical College and is still an adjunct professor of Biomedical Engineering at Cornell University, and is also the Gyula and Katica Tauber Professor, Emeritus, in biochemistry and chemistry at Brandeis University. On October 24, 2023, in a ceremony in the East Room of the White House, President Joe Biden presented Gregory Petsko and eight others with the National Medal of Science, the highest honor the United States can bestow on a scientist and engineer.

The NINCDS-ADRDA Alzheimer's Criteria were proposed in 1984 by the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association and are among the most used in the diagnosis of Alzheimer's disease (AD). These criteria require that the presence of cognitive impairment and a suspected dementia syndrome be confirmed by neuropsychological testing for a clinical diagnosis of possible or probable AD; while they need histopathologic confirmation for the definitive diagnosis. They specify as well eight cognitive domains that may be impaired in AD. These criteria have shown good reliability and validity.

<span class="mw-page-title-main">Posterior cortical atrophy</span> Medical condition

Posterior cortical atrophy (PCA), also called Benson's syndrome, is a rare form of dementia which is considered a visual variant or an atypical variant of Alzheimer's disease (AD). The disease causes atrophy of the posterior part of the cerebral cortex, resulting in the progressive disruption of complex visual processing. PCA was first described by D. Frank Benson in 1988.

<span class="mw-page-title-main">Alzheimer's disease</span> Progressive neurodegenerative disease

Alzheimer's disease (AD) is a neurodegenerative disease that usually starts slowly and progressively worsens, and is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems with language, disorientation, mood swings, loss of motivation, self-neglect, and behavioral issues. As a person's condition declines, they often withdraw from family and society. Gradually, bodily functions are lost, ultimately leading to death. Although the speed of progression can vary, the typical life expectancy following diagnosis is three to nine years.

Samuel E. Gandy, is a neurologist, cell biologist, Alzheimer's disease (AD) researcher and expert in the metabolism of the sticky substance called amyloid that clogs the brain in patients with Alzheimer's. His team discovered the first drugs that could lower the formation of amyloid.

<span class="mw-page-title-main">Rivastigmine</span> Chemical compound

Rivastigmine is a cholinesterase inhibitor used for the treatment of mild to moderate Alzheimer's disease. The drug can be administered orally or via a transdermal patch; the latter form reduces the prevalence of side effects, which typically include nausea and vomiting.

<span class="mw-page-title-main">Brain positron emission tomography</span> Form of positron emission tomography

Brain positron emission tomography is a form of positron emission tomography (PET) that is used to measure brain metabolism and the distribution of exogenous radiolabeled chemical agents throughout the brain. PET measures emissions from radioactively labeled metabolically active chemicals that have been injected into the bloodstream. The emission data from brain PET are computer-processed to produce multi-dimensional images of the distribution of the chemicals throughout the brain.

Florbetaben, a fluorine-18 (18F)-labeled stilbene derivative, trade name NeuraCeq, is a diagnostic radiotracer developed for routine clinical application to visualize β-amyloid plaques in the brain. It is indicated for Positron Emission Tomography (PET) imaging of β-amyloid neuritic plaque density in the brains of adult patients with cognitive impairment who are being evaluated for Alzheimer's disease (AD) and other causes of cognitive impairment. β-amyloid is a key neuropathological hallmark of AD, so markers of β-amyloid plaque accumulation in the brain are useful in distinguishing AD from other causes of dementia. The tracer successfully completed a global multicenter phase 0–III development program and obtained approval in Europe, US and South Korea in 2014.

<span class="mw-page-title-main">Krembil Research Institute</span>

The Krembil Research Institute, formerly known as the Toronto Western Research Institute, is an academic medical research institute in Toronto. It is one of the largest research institutes in Canada focusing on human neurological disease.

Michael D. Geschwind is a professor of neurology at the UCSF Memory and Aging Center (MAC), specializing in neurodegenerative disorders.

Rachelle Smith Doody is an American neurologist and neuroscientist. She is known for her work on late stage development of drugs for Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and other neurodegenerative disorders.

<span class="mw-page-title-main">Andrew E. Budson</span> American neurologist

Andrew E. Budson is an American neurologist, academic and researcher. He is a Professor of Neurology at Boston University School of Medicine, Lecturer in Neurology at Harvard Medical School, Chief of Cognitive and Behavioral Neurology and Associate Chief of Staff for Education at the Veterans Affairs (VA) Boston Healthcare System, where he also serves as a Director of the Center for Translational Cognitive Neuroscience. He is Associate Director and Outreach, Recruitment, and Engagement Core Leader at the Boston University Alzheimer’s Disease Research Center.

References

  1. ↑ "University Health Network, Researcher Profile".
  2. ↑ "Donald Weaver, Professor - Status". UofT LDFP. Retrieved 2023-04-24.
  3. ↑ "CAHS Fellows Directory – Canadian Academy of Health Sciences | Académie canadienne des sciences de la santé" . Retrieved 2023-04-24.
  4. 1 2 "Canada Research Chairs, Government of Candad".
  5. ↑ Meier‐Stephenson, Felix S.; Meier‐Stephenson, Vanessa C.; Carter, Michael D.; Meek, Autumn R.; Wang, Yanfei; Pan, Luzhe; Chen, Qiangwei; Jacobo, Sheila; Wu, Fan; Lu, Erhu; Simms, Gordon A.; Fisher, Laural; McGrath, Alaina J.; Fermo, Virgil; Barden, Christopher J. (January 2022). "Alzheimer's disease as an autoimmune disorder of innate immunity endogenously modulated by tryptophan metabolites". Alzheimer's & Dementia: Translational Research & Clinical Interventions. 8 (1): e12283. doi:10.1002/trc2.12283. ISSN   2352-8737. PMC   8985489 . PMID   35415204.
  6. ↑ Weaver, Donald F. (January 2020). "Amyloid beta is an early responder cytokine and immunopeptide of the innate immune system". Alzheimer's & Dementia: Translational Research & Clinical Interventions. 6 (1): e12100. doi:10.1002/trc2.12100. ISSN   2352-8737. PMC   7606184 . PMID   33163614.
  7. ↑ Kolaj, Igri; Wang, Yanfei; Ye, Kailin; Meek, Autumn; Liyanage, S. Imindu; Santos, Clarissa; Weaver, Donald F. (August 2021). "Ferulic acid amide derivatives with varying inhibition of amyloid-β oligomerization and fibrillization". Bioorganic & Medicinal Chemistry. 43: 116247. doi:10.1016/j.bmc.2021.116247. PMID   34157569. S2CID   235608263.
  8. ↑ Wang, Zhiyu; Wang, Yanfei; Pasangulapati, Jagadeesh Prasad; Stover, Kurt R.; Liu, Xiaojing; Schier, Stephanie (Wohnig); Weaver, Donald F. (October 2021). "Design, synthesis, and biological evaluation of furosemide analogs as therapeutics for the proteopathy and immunopathy of Alzheimer's disease". European Journal of Medicinal Chemistry. 222: 113565. doi:10.1016/j.ejmech.2021.113565. PMID   34118718.
  9. ↑ Zheng, Yong; Stafford, Paul M.; Stover, Kurt R.; Mohan, Darapaneni Chandra; Gupta, Mayuri; Keske, Eric C.; Schiavini, Paolo; Villar, Laura; Wu, Fan; Kreft, Alexander; Thomas, Kiersten; Raaphorst, Elana; Pasangulapati, Jagadeesh P.; Alla, Siva R.; Sharma, Simmi (2021-07-20). "A Series of 2‐((1‐Phenyl‐1H‐imidazol‐5‐yl)methyl)‐1H‐indoles as Indoleamine 2,3‐Dioxygenase 1 (IDO1) Inhibitors". ChemMedChem. 16 (14): 2195–2205. doi:10.1002/cmdc.202100107. ISSN   1860-7179. PMID   33759400. S2CID   232339495.
  10. ↑ "Appointments, Division of Neurology, Dalhousie University".
  11. ↑ "The Sobey Foundation gives $2M for Alzheimer's research chair". Dalhousie News. Retrieved 2023-04-24.
  12. ↑ Kisilevsky R, Szarek WA, Weaver DF. A method of treating amyloidosis. U.S. Patent No. 5,728,375, issued March 17, 1998.
  13. ↑ Kisilevsky R, Szarek WA, Weaver DF. A method of treating amyloidosis. U.S. Patent 5,643,562, issued July 01, 1997.
  14. ↑ Weaver, Donald F. (2021-03-23). "A Day That Changed Lives". Neurology. 96 (12): 583–585. doi:10.1212/WNL.0000000000011547. ISSN   0028-3878. PMC   8032366 . PMID   33504647.
  15. ↑ Weaver, Donald F. (2018-08-20). "In the Alzheimer waiting room". Canadian Medical Association Journal. 190 (33): E989–E990. doi:10.1503/cmaj.180320. ISSN   0820-3946. PMC   6102110 . PMID   30998498.
  16. ↑ Weaver, Donald F. (2016-07-26). "Alzheimer's disease: True enemy of humankind". Neurology. 87 (4): e33. doi:10.1212/WNL.0000000000002885. ISSN   0028-3878. PMC   4977108 .
  17. ↑ Weaver, D. F. (2014-08-26). "Alzheimer's: Three voices, one song". Neurology. 83 (9): e97. doi:10.1212/WNL.0000000000000738. ISSN   0028-3878. PMC   4155045 .
  18. ↑ "American Academy of Neurology | Awards History". www.aan.com. Retrieved 2023-04-24.
  19. ↑ "Aiming at Multiple Alzheimer's Proteins May be Key to Success | BrightFocus Foundation". www.brightfocus.org. Retrieved 2023-04-24.
  20. ↑ "Prix Galien | 2009 Laureates". prix-galien-canada.org. Retrieved 2023-04-24.
  21. ↑ Canada, Employment and Social Development (2010-03-15). "Eight Canadian scientists and scholars garner over $1 million in Killam Research Fellowships". www.canada.ca. Retrieved 2023-04-24.
  22. ↑ "Jonas Salk Recipients". www.marchofdimes.ca. Retrieved 2023-04-24.
  23. ↑ "Heinz Lehmann Award | JPN". www.jpn.ca. Retrieved 2023-04-24.
  24. ↑ "Donald Weaver, MD, PhD, FRCP(C) | Scholars | Harrington Discovery Institute at University Hospitals". www.harringtondiscovery.org. Retrieved 2023-04-24.
  25. ↑ "What if Alzheimer's is an autoimmune disease? Toronto neurologist awarded for work on unconventional hypothesis". The Globe and Mail. 2022-06-21. Retrieved 2023-04-24.
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