IRCM’s Centre on Rare and Genetic Diseases in Adults Sophie Bernard, M.D., PhD. Head of the Rare Disease Clinic, IRCM Director, Genetic Dyslipidemias Clinic, IRCM Assistant Professor, Department of Medicine, Montreal University Rare Disease Day Conference 2020 March 9-10

1. Sophie Bernard, M.D., PhD.
Head of the Rare Disease Clinic, IRCM
Director, Genetic Dyslipidemias Clinic, IRCM
Assistant Professor, Department of Medicine, Montreal University
IRCM’s Centre on Rare and
Genetic Diseases in Adults

2. § Founded in 1967, IRCM is a non-profit organization
that conducts basic and clinical biomedical research
in addition to training high-level scientists
§ The Institute :
üapproximatively 435 people (researchers, students and employees)
übrings together 35 basic and clinical research laboratories

3. IRCM’s Centre on Rare and Genetic Diseases in Adults
§ Out of 2.5 million Canadians affected by a rare disease, more than 500,000 come
from the province of Quebec.
§ The center was launched in 2016 to address the needs of these patients:
ØProviding access to specialized medical care
ØDeveloping a model to ensure transition from pediatric to adult care
ØCatalyzing translational research under the same roof (patients, clinicians, researchers)
to better understand a variety of rare diseases, and consequently, to develop new
treatments.
§ To date : 4 sub-specialized clinics are opened:
ØGenetic Dyslipidemias Clinic
ØPrimary Immunodeficiency Clinic
ØRare Kidney Diseases Clinic
ØPorphyria Clinic

4. The classical odyssey of people
with rare diseases
Unmet needs and approaches to improve the process
from diagnosis to treatment and social integration
Familial chylomicronemia syndrome as an example

5. Familial chylomicronemia syndrome (FCS)
MilkFCS
§ Genetic disorder : 1-10 affected people/ million
§ Founder effect in Quebec : 100-200 /million in some areas
§ Parents are not affected
Tremblay et al. J Clin Lipidol. 2011;5:37
Brahm AJ. Nat Rev Endocrinol. 2015;11:352
Ø Very low fat diet : < 15-20 g / day (1-11/2tbsp of oil)
Ø No alcohol, limited simple sugars
§ Impaired break down of fats leading to very high lipid particles
in the blood (chylomicrons)
§ Elevated risk of life threatening attacks of pancreatitis and early death

6. § Patients saw an average of 5
physicians before receiving the
appropriate diagnosis
§ almost 1/3 of patients are diagnosed
after puberty
Ø training of primary caregivers :
by elaborating a dedicated familial
residency teaching program
Ø close collaboration with patients
advocacy groups :
joint partnership with RQMO (Quebec
Coalition of Orphan Diseases)
The classical journey of people with rare diseases
FCS as an example
Diagnosis

7. § Transition from pediatric to adult care
ü Lost to follow-up :
increased risk of complications
§ Preconceptional
ü Misinformation
« You will never give birth »
Ø joint clinics with pediatricians and
adult clinicians
Ø primary care formation
Ø involvement of our team in
periconceptional and perinatal
departments
The classical journey of people with rare diseases
FCS as an example
Medical care and follow-up

8. The classical journey of people with rare diseases
FCS as an example
Treatment
§ Glybera : gene therapy
one of this country's great scientific achievement by a
team of researchers at the University of British Columbia
ØThis treatment changed Cynthia's life, ending the
pancreatitis attacks and giving her the chance to start
the family she thought she’d never have.
ØCynthia is now the proud mother of two young children
her "two miracles".
Ø Approved in Europe in 2012. Unfortunatly as the
drug was too expensive, the company stopped the
production
Dr. Danica Stanimirovic (NRC)
with partners at UBC try to develop
a new version of the therapy

9. The classical journey of people with rare diseases
FCS as an example
Treatment
Volanesorsen (Akcea Rx) :
§ Very good efficiency with almost 80%
reduction of chylomicrons
§ Not approved by FDA and Health
Canada because of the non significant
reduction of pancreatitis,
§ Available in Europe
Øurgent need to conceive small clinical
trials specifically adapted to rare diseases
ØIRCM is part of a board initiated by
Montreal inVivo and made up of small
compagnies, patients advocacy group
(RQMO), researchers and clinicians
The mission of this board is to accelerate
the development of innovative tools and
treatments for rare diseases

10. Adapted from Michael Davidson; et al; Expert Review of Cardiovascular Therapy 2017, 15, 415-423. Copyright © 2017 Informa UK Limited, trading as Taylor & Francis Group
§ Only 1 out of 5 patients has a full-time job
§ Time off from work per year : 30 days
(mean)
§ Over 50 % reported very high impact of the
disease on ability to fulfill reponsabilities
at school or work
The classical journey of people with rare diseases
FCS as an example
Psychosocial Impact : InFocus Online survey
Sponsored by Akcea Therapeutics

11. The classical journey of people with rare diseases
FCS as an example
Psychosocial Impact
§ Poor quality of life
§ Isolation
§ Especially during adolescence
§ Impact is multiple :
ü Adherence to diet, treatment and medical follow-up
ü Family life, relatives, partners
ü Fear of acute pancreatitis and hospitalization
ü Fear to give birth
ü Education and employment : choose careers below their level of abilities

12. Sadness and depression are the top
emotions, followed by frustration,
feeling abnormal, upset, and anxious
Ø Urgent need of psychosocial
ressources for patients and
families
Ø This study gives us important insights
of the disease from a patient’s
perspective that have been under-
recognized and not previously
characterized in literature
Ø We learned from patients and
families
IN-FOCUS: Quantifying the Severity and Frequency of the
Disease Burden: How Does FCS Make You Feel?
Michael Davidson; et al. Expert Review of Cardiovascular Therapy 2017, 15, 415-423.

13. A participatory-action research project aiming to understand and help
resolve morally problematic situations raised by rare diseases in Quebec
Ariane Quintal, B.Sc., M.A. 1,2; Gail Ouellette, Ph.D.3; Eric Racine, Ph.D.1,2,4
3
1
2
4
Observations Proposition of an action plan
e.g., educational tool, decision aide, dialogue tool
Follow-up interviews
Aim 1: Understand morally problematic
situations raised by rare diseases
Aim 3: Help resolve key
preoccupying situations
Aim 2: Identify which are the situations
that preoccupy patients the most
Online consultative survey
Living with a rare disease implies psychosocial and occupational obstacles, and thus, morally
problematic situations.
A morally problematic situation makes it difficult to choose or decide in light of tensions
between values, needs, and preferences of its stakeholders.
Rare diseases lead to morally problematic situations for patients, caregivers, and clinicians.
Our affiliations:
Funding:
Pragmatic Health Ethics

14. What next ?
§ Efforts should focus on :
Ø Reducing the isolation of patients, families and caregivers by expanding an
open network of researchers, clinicians, patients and advocacy groups
Ø Implementing a strategy for rare diseases supported by Canadian public policy
makers to provide patients better access to medical, community and
governmental resources.

15. IRCM Challenge, 2019, Mt-Royal Park, Montreal