Transcript CMD Clinical Trial Readiness Campaign

The CMD genes ~ The CMD to
LGMD spectrum
CMD
LGMD
Ullrich CMD (col6a1, col6a2,
col6a3)
Bethlem myopathy
Merosin deficient CMD
(LAMA2)
Dystroglycanopathies: FKRP,
fukutin, POMT1, POMT2,
POMGnT1, LARGE
Syndromic: WWS, MEB,
Fukuyama
SEPN1
Alpha 9 integrin
Lamin A/C
LGMD2K, LGMD2I, LGMD2L,
LGMD2N
Congenital Myopathy- RYR1
 There is an overlap between congenital muscular
dystrophy and congenital myopathy .
 CMD subtype: SEPN1 or Rigid Spine Muscular
Dystrophy can look exactly like Ryanodine Receptor
congenital myopathy on biopsy and clinical picture
 A decision to include Congenital Myopathy- RYR1 in
the CMDIR, as no exisiting registry, similar clinical
needs and overlapping targets in calcium handling.
 We welcome the RYR1 families!
Why do we care about Clinical
Trial Readiness?
Being ready means:
1. We maximize our chances of
getting a good drug to and through
clinical trial.
2. We are able to measure an effect
that the FDA accepts and is
meaningful to our community.
Why do trials fail to reach
clinically significant endpoints
or show a benefit in outcome
measure?
The drug has no effect, not the intended effect or the
size of the effect is not measurable.
The community was not “ready” to go to clinical
trials.
 no biomarkers
 not rigorous enough preclinical testing
 not enough known about the drug’s effect in the
population
 outcome measures that pick up big not subtle changes
 unable to reach a statistically significant number of
participants to show smaller effect
 rate of disease progression in participants too variable
Therapeutic
intervention
failure
identify a tight
cohort
identify clinical trial
design
Longitudinal
natural history
identify biomarkers
identify clinically
meaningful endpoints
validate outcome
measures
How do we measure functional gains in strength?
Current motor scales and timed tests
Effort dependent, how do the scales work in the setting of
contractures
Cure CMD Initiatives to Address
Clinical Trial Readiness
Subject
Speaker
CMD Standard of Care
Anne Rutkowski, Cure CMD Chairman
CMDIR
Ami Mehta, Lead Genetic Counselor
CMDIR
CMD BioBank
Tara Schimdlen, Genetic Counselor,
NIGMS Repository at Coriell
CMD Outcome Measures
Eunice Kim, Cure CMD Vice Chair
CMD Natural History study
Carsten Bonnemann, MD, NINDS
Cure CMD SMAB Chairman
Update on CMD Care Guidelines
 Led by Dr. Ching Wang, Dr. Thomas Sejersen and Cure
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CMD
CMD Standard of Care Committee (80 international
subspecialists)
CMD Clinician survey, subspecialist specific
CMD Family Standard of Care survey
CMD Care Guidelines Workshop, Brussels Nov 2009
Revisions
CMD Care Guidelines. Submitted for Publication
After publication, distribution of Care Guidelines
Next step…..CMD Family Friendly Care Guidelines
Why are CMD Care Guidelines
important?
Assist doctors who have never seen a CMD patient
offer a standard approach to work up (diagnosis) ,
referrals to subspecialists and an understanding of
care issues
2. This results in more PRO-ACTIVE CMD medical
care in the global community.
3. Assists families and affected individuals be informed
about appropriate care and anticipate upcoming care
issues
4. An important part of CMD clinical trial readiness
1.
Future directions
Publication and adoption of CMD Care guidelines
(physician and lay friendly versions)
2. Identification of different medical practices that
might benefit people with CMD if adopted on a
broader scale
3. Identification of areas of uncertainty in CMD
medical practice, develop hypothesis, fund clinical
trials to determine best practices that improve and
save lives.
1.
What do we all want?
A scientific investment that delivers a drug to slow
disease progression, buys time, and improves quality
of life
Earlier diagnosis with genetic confirmation (if possible)
Less variable, more proactive medical care from the
global medical community with an emphasis on
multidisciplinary care