Duchenne in 2013 DUCHENNE IN 2013 Cape Town, February 2013 Doug Biggar MD Muscular Dystrophy Foundation Holland Bloorview Doug Kids Biggar Rehabilitation Hospital Capetown, February2013
Objectives for today Impact of corticosteroids on natural history Hurdles for new therapies New strategies for treatment Therapeutic dose of HOPE
Today Boys Become Adults With Adult Needs
Steroids the Good: So most agree that: Corticosteroids help muscle strength They slow the progression of muscle weakness Best to start when boys are walking Best to give once a day, every day if you can Balanced discussion of benefits and risks More studies are needed
What is Good? Short-term Most boys, but not all, have more energy Long-term Walking Breathing Heart Spine Arm strength
Preserved Muscle Function
Walking No corticosteroids stop around 10 years old With corticosteroids walk 3-5 years longer
Better Pulmonary Function
FVC Percent Predicted PULMONARY FUNCTION 100 80 60 40 Untreated Treated 20 0 10 15 18 Age in years
Pulmonary Function At 18 years, boys on steroids should have: Fewer lung infections A better cough Fewer admissions to hospital for pneumonia Very few need night time ventilation
Preserved Cardiac Function
Cardiac Function-2011 10-20 yr. - prospective Control n=26 Deflazacort n=67 P Age 15.5 14.8 NS LVEF (<45%) 70 % 5% <0.001
Delayed Scoliosis
Scoliosis Surgery No steroids 90% boys done around 15 years Need help feeding after surgery Steroid treated: Only 10%, not 90%, of boys done at 15-17 years Can self feed after surgery
Steroids: the Bad Variable and can include: Shorter height Reduced bone health Weight gain Delayed puberty And more
You will be short
But that could be good, no?
What about bones?
What makes bones healthy? Genetics 70-80% Physical activity Other things: calcium, vitamin D etc
What about my son s bones? Even young boys have reduced bone density Worse with less walking ~35% break a long bone (leg or arm), with or without steroids Vertebral (back bone) fractures only occur on steroids
Soooo..How bad? Probably not worse with deflazacort Risk of fractures: long bones vertebrae Can be treated, if needed More research needed
And puberty? It will be delayed. It will happen. But while you are waiting. you will look younger than you are no facial hair high voice BUT no pimples no need to shave
And Weight gain, can be bad Some boys are thin, no problem. Some boys gain a lot of weight, even not on steroids- big problem. Most boys: big appetite less active want treats like all boys a real challenge for most families
What is the bottom line?
This is one bottom line?
The bottom line:. The good must be better than the bad Major benefits include improved: Skeletal muscles Pulmonary Cardiac Scoliosis Arm strength
Living with Duchenne Can be difficult but many of the issues are not medical but rather psychosocial. I worry less about premature death than my social isolation, adult friends, job. My aspirations are like yours: good job, friends, a partner and family.
Therapeutic Strategies Gene transfer Cell therapies Up regulation of alternative proteins Increase muscle bulk Focus on downstream pathology Modify the mutation: exon skipping, stop codon suppression
Hurdles for Treatments Animal models Biomarkers Delivery Host immune response Clinical variability Outcome measures
Therapeutic Dose of HOPE New understanding Better science and resources Partnerships: parents, science & industry Patient registries Regulators understanding Ethics Review Boards
LIFE CAN BE A GOOD RIDE
THANK YOU THANK YOU!
THANK YOU THANK YOU!
CARE Guidelines Consensus process Scientific publication Dissemination to: Families Care providers Policy makers Revise & update
Using Knowledge to Improve Care The diagnosis and management of Duchenne Muscular Dystrophy: Lancet Jan/Feb 2010
Using Knowledge to Improve Care The diagnosis and management of Duchenne Muscular Dystrophy: Lancet Jan/Feb 2010
Bottom Line: Common side effects: Short Delayed puberty Vertebral fragility fractures Weight gain
What are the Unknowns? Benefits of prednisone over deflazacort? When is the best time to start? What is the best dose to use at different ages? Do steroids help all boys? Do you ever stop steroids? When will there be a drug with only the good effects and not the bad?