The Advent of Precision Medicine for Parkinsons Disease James Beck, - - PowerPoint PPT Presentation

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The Advent of Precision Medicine for Parkinsons Disease James Beck, - - PowerPoint PPT Presentation

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The Advent of Precision Medicine for Parkinsons Disease James Beck, PhD Chief Scientific Officer November 28, 2018 Todays Conversation Who We Are Ensuring Our effort to understand better care Parkinsons for everyone

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James Beck, PhD Chief Scientific Officer

The Advent of Precision Medicine for Parkinson’s Disease

November 28, 2018

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Today’s Conversation

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Ensuring better care for everyone with PD Understanding PD through research Educating & empowering the Parkinson’s community

  • Who We Are
  • Our effort to understand

Parkinson’s

  • Precision Medicine Initiative
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About the Parkinson’s Foundation

The Parkinson’s Foundation makes life better for people with Parkinson’s disease by improving care and advancing research toward a cure. In everything we do, we build on the energy, experience and passion of our global Parkinson’s community.

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CONFIDENTIAL

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We Are a National Organization

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Our Impact

Receives care at a designated Parkinson's Center of Excellence clinic Participates in the Parkinson’s Outcomes Project Calls the Helpline Receives care from a physical therapist trained by the Foundation Organizes a team for Moving Day, A Walk for Parkinson’s Engages as a Research Advocate in grant reviews and clinical trials

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Engagement Has Real Impact

Both qualitative and quantitative research suggest

  • utcomes are

better for those engaging with the Foundation.

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Not Engaged

60% Take control Persona 48% 43% Medical care is excellent 24% 48% Very informed @ treatment options 34% 71% Being treated by a Neurologist 74% 50% by a Movement Disorder Specialist 19% 57% by a Primary Care Physician 75% 66% Physical health excellent/good 43% 34% Physical health fair/poor 58% 63% Mental health excellent/good 43% 36% Mental health fair/poor 58% 29% Participated in clinical trial 5%

Engaged

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Get Involved

Moving Day Walk Parkinson’s Champions Advocate Support Us Volunteer Share Your Story Local Resources Find an Event

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Strong Community Support

$0 $5 $10 $15 $20 $25 $30 $35 2014 2015 2016 2017 2018

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Fiscal Year (audited) Millions

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Understanding Parkinson’s through Research

We invest more than $10 million annually in promising scientists who are

  • n a mission to understand

the basic mechanisms of Parkinson’s that are critical to developing new treatments and medications.

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2018 Grant Opportunities

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Beth Vernaleo, PhD Director, Research Programs

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Microsoft, 1978

Last major study was done in 1978 in Copiah County, Mississippi. 26 cases of PD found… …extrapolated to entire US population.

Who has Parkinson’s disease?

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https://www.nature.com/articles/s41531-018-0058-0

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Parkinson.org/statistics

Results now suggest 1 million people with PD by 2020

  • est. 85,000

California

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Parkinson’s Outcomes Project

Data collection on People with PD

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Fernando Cubillos, MD Senior Director, Research Programs

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Parkinson’s Outcomes Project

  • Better understand PD
  • Understand best care
  • What experts do to achieve

great outcomes

  • Improve care
  • Improve survival
  • Improve quality of life
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CONFIDENTIAL

Parkinson’s Outcomes Project

  • Ongoing longitudinal observational study initiated in 2009
  • Enrolled > 12,000 PD patients at 29 Centers of Excellence
  • Patient Registry includes demographic data, clinical history and

disease status, as well as medications and treatments. Patient assessments of PD related disabilities (PDQ39), and data relating to caregiver burden (MCSI) are also captured.

  • De-identified data made available to clinicians andthe research

community

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CONFIDENTIAL

Parkinson’s Outcomes Project: Major Findings

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2018

  • Management of PD 20 years: digital health pathways
  • Clinical factors for clinician certainty in iPD diagnosis
  • Baseline predictors of falls in PD
  • Time to PD psychosis diagnosis and treatment

initiation

  • Baseline predictors of greatest change in QoL

2016

  • Gender differences in the clinical

progression of PD

  • Profile of individuals with PD referred

to allied health

  • Hospital care for mental health and

substance abuse in PD

  • Baseline characteristics that predict greatest

improvement in Quality of Life after DBS

  • Higher risk of cognitive impairment in PD with

comorbid diabetes

2017

The Parkinson’s Outcomes Project can be leveraged by external groups to deploy sub-studies/questionnaires within the study population and link phenotypic and genotypic data

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Alpha Synuclein Parkin PINK1 DJ-1 LRRK2 GBA Unknown

Causes of Parkinson’s Disease

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Idiopathic (unknown) PD Genetic or Familial PD ~20% ~80%

90% of all cases are of unknown origin

– called sporadic or idiopathic Parkinson’s

10% (maybe up to 20%) of all cases are thought to have a genetic component Parkinson’s is likely due to a combination of genes and environment (multifactorial)

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Kumaran and Cookson 2015

What are the PD Genes?

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Kumaran and Cookson 2015

PD “Risk Factor” Genes

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Who has the PD Genes?

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Idiopathic (unknown) PD Genetic or Familial PD ~20% ~80%

If very few have PD genes, why do we care?

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Dodo, 2006

A tale of genes…

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Jim Fixx died at 52 Winston Churchill died at 90

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Who has the PD Genes?

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Idiopathic (unknown) PD Genetic or Familial PD ~20% ~80%

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Kumaran and Cookson 2015

LRRK2 and GBA

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LRRK2 Mutations

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  • LRRK2 – Identified in 2004, an enzyme with unknown function, represent

about 1% of all people with PD, 5% of those with PD in their family and 15% of Ashkenazi Jews.

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GBA1 Mutations

28 Liu et al. 2016

  • GBA – linked to PD in 2009, double

mutations lead to Gaucher’s disease, GBA variants are present in 5-10% of whites and 20% of Jews.

Hruska et al. 2016

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200 participants

Next Generation Clinical Trials

Targeting GBA:

– NCT02906020 – (GZ/SAR402671, venglustat) – Sanofi/Genzyme (MOVES- PD), glucosylceramide synthase inhibitor

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Others on the way! Merck, GSK, Biogen, Allergan, Cerevel, Prevail, and more!

~1000 participants for 5 phase 2; ~4,000 for phase 3

Targeting LRRK2:

NCT03710707 – (DNL201) – Denali Therapeutics, LRRK2 enzyme inhibitor, Phase Ib (30 people)

The Future is HERE

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Next Generation Clinical Trials

We are not ready….

  • Vast majority do not know their carrier status
  • Those who did DTC genetic testing only had 1-2

variants of LRRK2 tested, GBA recently added but not key disease variants

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The Future is HERE….but

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What does 23&Me report?

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Reporting is not comprehensive for PD LRRK2 GBA

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Next Generation Clinical Trials

Relying on drug companies to offer genetic testing may lead to Balkanization

  • f genetic information,

hindering progress.

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Driving the community…

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Aim 1: Accelerate Precision Medicine Clinical Trials for PD Aim 2: Unlock the Potential of Precision Medicine for Improved PD Care and Research Aim 3: Empower Patients (to take control of their disease)

Anna Naito, PhD Director, Research Programs

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CONFIDENTIAL

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PD GENEration Steering Committee

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Roy Alcalay, MD Columbia University SAB Member; Steering Committee Chair Karen Marder, MD Columbia University Martha Nance, MD Park Nicollet, Minneapolis Tanya Simuni, MD Northwestern University Michael Schwarzschild, MD, PhD Mass General Hospital Anne Hall, JD Parkinson’s Research Advocate

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PD GENEration

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Begin enrollment in Spring 2019 Six pilot sites: Northeast, Midwest, and West coast Goal: 600 participants in ~12 months Expansion phase: COEs plus PSG sites (~50 in total) Goal: 15,000 total participants in 5 years

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Questions and Discussion

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Award Programs

  • Awards for institutions
  • Institutional Movement Disorder Fellowships
  • Research Centers of Excellence
  • Awards for independent investigators
  • Stanley Fahn Junior Faculty Award
  • Clinical Research Award
  • Impact Awards
  • Conference Awards
  • Fellowships and early career awards
  • Postdoctoral Fellowships
  • Melvyn Yahr Early Career Award in Movement Disorders Research
  • Parkinson’s Foundation-APDA Summer Fellowships
  • Visiting Scholar Awards
  • Partnership awards with American Brain Foundation and Parkinson Study Group

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Research Centers of Excellence: Award Details

  • Award is $2,000,000 total: $500,000/year for 4 years
  • Up to 10% ($50,000/year) may be budgeted for indirect costs
  • We anticipate funding 2-4 Centers this year
  • Each Center will have a thematic area to be researched
  • Institutions must have a proven track record in research
  • Expertise that each PI brings to the Center
  • Synergy between PI, departments, and institutions as applicable
  • Each year, $50,000 must be reserved for pilot projects or new collaborations
  • Special consideration will be given to institutions that are able to match

Foundation funds.

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