Lewy body dementia: Overcoming barriers and identifying solutions

Kanishka Agarwal¹, Wendi Backler¹, Ece Bayram², Leah Bloom³, Bradley F Boeve⁴, Jang-Ho Cha⁵, Maria Denslow⁶, Tanis J Ferman⁷, Douglas Galasko⁸, James E Galvin⁹, Stephen N Gomperts¹⁰, Michael C Irizarry⁶, Kejal Kantarci¹¹, Harsh Kaushik¹, Matt Kietlinski¹, Aaron Koenig¹², James B Leverenz¹³, Ian McKeith¹⁴, Pamela J McLean¹⁵, Thomas J Montine¹⁶, Sandra O Moose¹, John T O'Brien¹⁷, Valery Panier¹, Sharad Ramanathan¹⁸, Michael S Ringel¹, Sonja W Scholz^{19

20}, Jonnell Small¹, Reisa A Sperling^{10

21}, Angela Taylor²², John-Paul Taylor¹⁶, Rebecca A Ward¹⁰, Lisa Witten¹, Bradley T Hyman¹⁰

Affiliations

¹ The Boston Consulting Group, Boston, Massachusetts, USA.
² Parkinson and Other Movement Disorders Center, Department of Neurosciences, University of California San Diego, La Jolla, California, USA.
³ Zag Bio, Inc, Cambridge, Massachusetts, USA.
⁴ Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
⁵ Latus Bio, Cambridge, Massachusetts, USA.
⁶ Alzheimer Disease and Brain Health, Eisai, Inc., Nutley, New Jersey, USA.
⁷ Department of Psychiatry and Psychology, Mayo Clinic, Jacksonville, Florida, USA.
⁸ Department of Neurosciences, and Shiley-Marcos Alzheimer's Disease Research Center, UC San Diego, La Jolla, California, USA.
⁹ Department of Neurology, Comprehensive Center for Brain Health, University of Miami Miller School of Medicine, Boca Raton, Florida, USA.
¹⁰ Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA.
¹¹ Department of Radiology, Division of Neuroradiology, Mayo Clinic Rochester, Rochester, Minnesota, USA.
¹² Delix Therapeutics, Bedford, Massachusetts, USA.
¹³ Cleveland Lou Ruvo Center for Brain Health, Neurological Institute, Cleveland Clinic, Cleveland, Ohio, USA.
¹⁴ Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.
¹⁵ Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
¹⁶ Department of Pathology, Stanford University, Stanford, California, USA.
¹⁷ Department of Psychiatry, University of Cambridge School of Clinical Medicine, Cambridge, UK.
¹⁸ Departments of Molecular and Cell Biology, Stem Cell and Regenerative Biology and Applied Physics, Harvard University, Cambridge, Massachusetts, USA.
¹⁹ National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
²⁰ Department of Neurology, Johns Hopkins University Medical Center, Baltimore, Maryland, USA.
²¹ Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
²² Lewy Body Dementia Association, Lilburn, Georgia, USA.

PMID: 38265159
PMCID: PMC10942666
DOI: 10.1002/alz.13674

Lewy body dementia: Overcoming barriers and identifying solutions

Kanishka Agarwal et al. Alzheimers Dement. 2024 Mar.

. 2024 Mar;20(3):2298-2308.

doi: 10.1002/alz.13674. Epub 2024 Jan 24.

Authors

Affiliations

¹ The Boston Consulting Group, Boston, Massachusetts, USA.
² Parkinson and Other Movement Disorders Center, Department of Neurosciences, University of California San Diego, La Jolla, California, USA.
³ Zag Bio, Inc, Cambridge, Massachusetts, USA.
⁴ Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
⁵ Latus Bio, Cambridge, Massachusetts, USA.
⁶ Alzheimer Disease and Brain Health, Eisai, Inc., Nutley, New Jersey, USA.
⁷ Department of Psychiatry and Psychology, Mayo Clinic, Jacksonville, Florida, USA.
⁸ Department of Neurosciences, and Shiley-Marcos Alzheimer's Disease Research Center, UC San Diego, La Jolla, California, USA.
⁹ Department of Neurology, Comprehensive Center for Brain Health, University of Miami Miller School of Medicine, Boca Raton, Florida, USA.
¹⁰ Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA.
¹¹ Department of Radiology, Division of Neuroradiology, Mayo Clinic Rochester, Rochester, Minnesota, USA.
¹² Delix Therapeutics, Bedford, Massachusetts, USA.
¹³ Cleveland Lou Ruvo Center for Brain Health, Neurological Institute, Cleveland Clinic, Cleveland, Ohio, USA.
¹⁴ Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.
¹⁵ Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
¹⁶ Department of Pathology, Stanford University, Stanford, California, USA.
¹⁷ Department of Psychiatry, University of Cambridge School of Clinical Medicine, Cambridge, UK.
¹⁸ Departments of Molecular and Cell Biology, Stem Cell and Regenerative Biology and Applied Physics, Harvard University, Cambridge, Massachusetts, USA.
¹⁹ National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
²⁰ Department of Neurology, Johns Hopkins University Medical Center, Baltimore, Maryland, USA.
²¹ Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
²² Lewy Body Dementia Association, Lilburn, Georgia, USA.

PMID: 38265159
PMCID: PMC10942666
DOI: 10.1002/alz.13674

Abstract

Despite its high prevalence among dementias, Lewy body dementia (LBD) remains poorly understood with a limited, albeit growing, evidence base. The public-health burden that LBD imposes is worsened by overlapping pathologies, which contribute to misdiagnosis, and lack of treatments. For this report, we gathered and analyzed public-domain information on advocacy, funding, research outputs, and the therapeutic pipeline to identify gaps in each of these key elements. To further understand the current gaps, we also conducted interviews with leading experts in regulatory/governmental agencies, LBD advocacy, academic research, and biopharmaceutical research, as well as with funding sources. We identified wide gaps across the entire landscape, the most critical being in research. Many of the experts participated in a workshop to discuss the prioritization of research areas with a view to accelerating therapeutic development and improving patient care. This white paper outlines the opportunities for bridging the major LBD gaps and creates the framework for collaboration in that endeavor. HIGHLIGHTS: A group representing academia, government, industry, and consulting expertise was convened to discuss current progress in Dementia with Lewy Body care and research. Consideration of expert opinion,natural language processing of the literature as well as publicly available data bases, and Delphi inspired discussion led to a proposed consensus document of priorities for the field.

Keywords: Lewy body dementia; funding sources; natural language processing; research trends.

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Conflict of interest statement

The opinions expressed in this article are the author's own and do not reflect the view of the National Institutes of Health, the Department of Health and Human Services, or the United States government. At the time of the research, K.A., W.B., H.K., M.K., S.O.M., V.P., M.S.R., J.C.S., and L.W. were employees of Boston Consulting Group which funded the research for this article through BCG's health care practice. B.F.B. is an investigator for clinical trials sponsored by Biogen, Alector, EIP Pharma, Cognition Therapeutics, and Transposon; a Scientific Advisory Board member for the Tau Consortium, AFTD, LBDA, and GE HealthCare; and serves as a member of the Data Safety Monitoring Board for a clinical trial on mesenchymal stem cells in MSA. J.H.C. is a former employee of Novartis, current employee and stockholder of Latus Bio, Inc., and serves as a member of the Comprehensive Center for X‐Linked Parkinsons Dementia (CCXD) Scientific Advisory Board. M.D. and M.C.I. are employees of Eisai, Inc., which has drug development programs in neurodegenerative disease. D.G. is a consultant for GE Healthcare. J.E.G. provides consultations to Biogen, BMS, Eisai, Eli Lilly, GE Healthcare, and Lundbeck, serves on the advisory board for Passage Bio, is the Chief Scientific Officer and stockholder at Cognivue which develops cognitive assessment tools. S.G. consults for EIP Pharma and serves on the advisory boards of Hillhurst Biopharmaceuticals, EIP Pharma, and the LBDA RCOE. K.K. consults for Biogen and serves on a Data Safety Monitoring Board at Takeda. A.K., holds stock in Sage Therapeutics and Delix Therapeutics. J.B.L. serves as an advisor for LBDA and the Cleveland Alzheimer's Association Chapter Board. J.T.O. consults for Biogen and Roche, serves on advisory boards for TauRx, NovoNordisk, Lilly, and the Lewy Body Society, as well as chairs the Research Strategy Council for the Alzheimer's Society. S.W.S. serves on the Scientific Advisory Council of the Lewy Body Dementia Association; receives research support from Cerevel Therapeutics; and serves on the scientific advisory council for the LBDA and Multiple System Atrophy Coalition. R.S. consults for AbbVie, AC Immune, Acumen, Alector, Alnylam, Bristol Myers Squibb, Genentech, Janssen, JOMDD, Nervgen, Neuraly, Neurocentria, Oligomerix, Prothena, Renew, Roche, Shionogi, Vigil Neuroscience, Ionis, and Vaxxinity. A.T. is an employee of the Lewy Body Dementia Association. J.P.T. consults for EIP Pharma, Kyowa‐Kirin, and Sosei‐Heptares; and serves on the scientific advisory committee for the LBDA and the Lewy Body Society. R.A.W. provided freelance medical writing services for this manuscript. The following authors have no additional disclosures (funding support related to this manuscript is listed above): E.B., L.B., T.J.F., B.H., I.M., P.J.M., T.M., and S.R. Author disclosures are available in the S2.

Figures

**FIGURE 1**
Cumulative funding from NIH and foundations. The semantic network of ∼1k projects funded by NIH in the field of “Lewy Body Dementia.” The proximity of clusters indicates technology affinity/overlapping. ∼30 projects could not be clustered. Funding amounts are based on 2.2k projects related to ”Lewy Body Dementia" funded by NIH Growth measured as CATR. Dot size is associated with the amount of funding associated with each grant. *Source*: NIH, BCG analysis BCG Center for Growth & Innovation Analytics. BCG, Boston Consulting Group; NIH, National Institutes of Health

**FIGURE 2**
Analysis of LBD publication landscape. The semantic network of ∼2.6k articles in the field of “Lewy Body Dementia” published since 2016. The proximity of clusters indicates technological affinity/overlapping. ∼40 articles could not be clustered and hence not shown in the above analysis. *Source*: Web of Science, BCG analysis BCG Center for Growth & Innovation Analytics. BCG, Boston Consulting Group; LBD, Lewy body dementia

**FIGURE 3**
Growth of grant funding and articles in the top 10 areas of LBD research. Lysosomal Glucocerebrosidase activity/functions excluded from plot due to too low n to calculate CAGR; Caregiving/cognition rehab excluded due to out of scope of workshop focus. Growth measured by CAGR. CAGR values for ‘3′ calculated using 2017–2021 data. Projects under “Alpha‐synuclein Targeting Therapeutic Approaches” categorized as “Drug discovery/drug target identification.” *Source*: BCG analysis and Lee et al.^7. BCG, Boston Consulting Group; CAGR, compound annual growth rate; LBD, Lewy body dementia

**FIGURE 4**
LBD, AD, and PD therapeutic pipeline. *Source*: www.clinicaltrials.gov. AD, Alzheimer's disease; LBD, Lewy body dementia; PD, Parkinson's disease

**FIGURE 5**
The potential impact and likelihood of success for identified LBD priorities. The outcome of the first (A) and second (B) votes for the prioritization of key approaches and likelihood of success by the Delphi method. LBD, Lewy body dementia

See this image and copyright information in PMC

References

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Lewy body dementia: Overcoming barriers and identifying solutions

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Lewy body dementia: Overcoming barriers and identifying solutions

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