The Advent of Precision Medicine for Parkinson’s Disease James Beck, PhD Chief Scientific Officer November 28, 2018
Today’s Conversation • Who We Are • Ensuring Our effort to understand better care Parkinson’s for everyone with PD • Precision Medicine Initiative Educating & Understanding empowering PD through the Parkinson’s research community 1
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. 2
We Are a National Organization CONFIDENTIAL 4
Our Impact Receives care at Participates in a designated the Parkinson’s Parkinson's Outcomes Center of Project Excellence clinic Receives care from a physical Calls the therapist Helpline trained by the Foundation Organizes a Engages as a team for Research Moving Day, A Advocate in Walk for grant reviews Parkinson’s and clinical trials
Engagement Has Real Impact Both qualitative 60% Take control Persona 48% and quantitative 43% Medical care is excellent 24% research suggest Engaged Not Engaged 48% Very informed @ treatment options 34% outcomes are 71% Being treated by a Neurologist 74% better for those 50% by a Movement Disorder Specialist 19% 57% by a Primary Care Physician 75% engaging with 66% Physical health excellent/good 43% the Foundation. 34% Physical health fair/poor 58% Mental health excellent/good 63% 43% 36% Mental health fair/poor 58% 29% Participated in clinical trial 5% 6
Get Involved Moving Day Walk Volunteer Parkinson’s Share Your Story Champions Local Advocate Resources Find an Event Support Us
Strong Community Support $35 $30 $25 Millions $20 $15 $10 $5 $0 2014 2015 2016 2017 2018 Fiscal Year (audited) 9
Understanding Parkinson’s through Research We invest more than $10 million annually in promising scientists who are on a mission to understand the basic mechanisms of Parkinson’s that are critical to developing new treatments and medications. 10
2018 Grant Opportunities Beth Vernaleo, PhD Director, Research Programs 11
Who has Parkinson’s disease? Last major study was done in 1978 in Copiah County, Mississippi. Microsoft, 1978 26 cases of PD found… …extrapolated to entire US population. 12
https://www.nature.com/articles/s41531-018-0058-0
Parkinson.org/statistics est. 85,000 California Results now suggest 1 million people with PD by 2020
Parkinson’s Outcomes Project Fernando Cubillos, MD Senior Director, Research Programs Data collection on People with PD 15
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
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 CONFIDENTIAL 17
Parkinson’s Outcomes Project: Major Findings -Gender differences in the clinical -Management of PD 20 years: digital health pathways progression of PD -Clinical factors for clinician certainty in iPD diagnosis -Profile of individuals with PD referred -Baseline predictors of falls in PD to allied health -Time to PD psychosis diagnosis and treatment -Hospital care for mental health and initiation substance abuse in PD -Baseline predictors of greatest change in QoL 2017 2016 2018 -Baseline characteristics that predict greatest improvement in Quality of Life after DBS -Higher risk of cognitive impairment in PD with comorbid diabetes 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 CONFIDENTIAL 18
Causes of Parkinson’s Disease 90% of all cases are of unknown origin Genetic or Familial PD – called sporadic or idiopathic Parkinson’s ~20% 10% (maybe up to 20%) of all cases are thought to have a genetic component Alpha Synuclein Parkin Parkinson’s is likely due to a PINK1 Idiopathic DJ-1 combination of genes and (unknown) PD LRRK2 environment (multifactorial) GBA ~80% Unknown 20
What are the PD Genes? Kumaran and Cookson 2015 21
PD “Risk Factor” Genes Kumaran and Cookson 2015 22
Who has the PD Genes? Genetic or ~20% Familial PD If very few have PD genes, why do we care? Idiopathic (unknown) PD ~80% 23
A tale of genes… Jim Fixx Winston Churchill died at 52 died at 90 Dodo, 2006 24
Who has the PD Genes? Genetic or ~20% Familial PD Idiopathic (unknown) PD ~80% 25
LRRK2 and GBA Kumaran and Cookson 2015 26
LRRK2 Mutations • 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. 27
GBA1 Mutations • 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 Liu et al. 2016 28
Next Generation Clinical Trials The Future is HERE Targeting GBA: – NCT02906020 – (GZ/SAR402671, venglustat) – Sanofi/Genzyme (MOVES- PD), glucosylceramide synthase inhibitor Targeting LRRK2: NCT03710707 – (DNL201) – Denali 200 participants Therapeutics, LRRK2 enzyme inhibitor, Phase Ib (30 people) Others on the way! Merck, GSK, Biogen, Allergan, Cerevel, Prevail, and more! ~1000 participants for 5 phase 2; ~4,000 for phase 3 29
Next Generation Clinical Trials The Future is HERE …. but 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 31
What does 23&Me report? LRRK2 GBA Reporting is not comprehensive for PD 32
Next Generation Clinical Trials Relying on drug companies to offer genetic testing may lead to Balkanization of genetic information, hindering progress. 33
Driving the community… Anna Naito, PhD Director, Research Programs 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) 34
35 CONFIDENTIAL
PD GENEration Steering Committee Michael Schwarzschild, Roy Alcalay, MD Tanya Simuni, MD MD, PhD Columbia University Northwestern University Anne Hall, JD Mass General Hospital SAB Member; Parkinson’s Research Steering Committee Chair Martha Nance, MD Karen Marder, MD Advocate Park Nicollet, Minneapolis Columbia University 36
PD GENEration 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 37
Questions and Discussion 38
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 39
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. 40
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