May is a month to celebrate mothers. PPMD’s dedication to mothers in our community is, in small part, reflected in our dedication to doing all we can to care for female carriers of Duchenne. The PPMD sponsored Carrier Study, ongoing at Nationwide Children’s Hospital in Columbus, Ohio, is being conducted by a team of experts in Duchenne as well as cardiology, neurology, and psychology.  While they agreed that they will be ready to reveal their findings at PPMD’s Annual Conference, June 28-July 1 in Arizona, we asked them to give a brief summary of their study and some “teasers” of the results they are excited to reveal.

From the Nationwide Carrier Study Team:

As we approach Duchenne Carrier Month, Nationwide Children’s Hospital Carrier Study team is pleased to offer a comprehensive clinical research evaluation for family members who are suspected carriers of the Duchenne or Becker muscular dystrophy. The goal of this study is to provide the best health care for carriers of the disease causing gene that potentially threatens well-being. Carriers of the gene can have both skeletal muscle symptoms (weakness, fatigue, muscle cramping, and pain) and cardiac manifestations, including compromised function potentially needing treatment. The information from the study is important for those requiring surgery or hospitalization for events like an unanticipated accident. There is also a major stress component that result from the intense care and concerns for affected children in the family with Duchenne or Becker.  It is our goal to thoroughly assess all health related issues as part of a comprehensive study funded by PPMD.

One of the worries of all Duchenne and Becker mothers and family members starts with whether they are in fact carriers. This question is addressed by DNA testing for the Duchenne gene.  On the one hand, the mother could have inherited the gene, and if so, this person has the most risk. We call them “Somatic Carriers”. In contrast there are many Mothers who had a spontaneous mutation that led to the affected child. This occurred in the ovary or at the time of fertilization and we refer to mothers with negative DNA tests as “Non-Somatic Carriers”. The full battery of extensive testing to be completed requires a two-day commitment. This will include seeing neuromuscular specialists (a doctor with expertise in muscular dystrophy and members of highly experienced physical therapy team) who check symptoms and signs of skeletal muscle involvement including a blood test for creatine kinase (CK). Studies then include extensive studies of cardiac function, including a physical exam, treadmill testing, and magnetic resonance imaging of the heart. The psychological impact is also thoroughly assessed using surveys and cognitive testing.

At this time, 75 mothers of Duchenne or Becker children have been evaluated. We also assessed 26 women volunteers who kindly agreed to go through testing assuring that the findings we discovered are due specifically to the carrier state and not merely incidental. The study has been highly successful and informative thus far. One of the control subjects wrote about her experience for the local newspaper, the Columbus Dispatch.

Having such a large number of participants has begun to elucidate differences in the studied populations; the following are some interim findings from the study:

• Cardiac scarring has been observed in nearly half of Somatic Carriers.
• The behavioral team has revealed numerous insights into the similar experiences and challenges of caring for a chronically ill child that are shared by the families in the Duchenne & Becker community.
• Their IQ-testing has shown no significant differences in cognitive ability between carriers and Non-Somatic/Control groups.
• Additional studies will specifically address how much caregiver stress, physical and/or emotional, contributes to cardiac scarring and compromise of cardiac function.
• We will determine if there are any biomarkers (e.g., blood tests, hair samples) that can serve to gauge the stress of the family environment.
• Muscle strength has been measured through the use of quantified knee extension strength; utilizing this assessment the team’s physical therapists have identified weakness associated with the carrier state.
• An unanswered question is whether loss of strength is progressive over time. Interestingly, elevated CK levels in carriers are not invariably predictive of muscle weakness in Somatic Carriers.
• Additional studies would be useful to test for CK isoenzymes to differentiate skeletal muscle as a source of CK verses heart muscle.

The team members at Nationwide Children’s Hospital are very excited to share these and many more findings with the community this summer at the 2018 PPMD Annual Conference in Scottsdale, AZ. The subsequent publications will be valuable for alerting the medical community to necessary care for carriers including emotional support for all family members affected by this disease. Individuals interested in participating (women age ≥18) who are at risk for being a carrier for Duchenne or Becker, including those who do not have an affected child, should contact the study coordinator at Eric.camino@nationwidechildrens.org or 614-722-2715.

Are you a Carrier?

PPMD is excited to have begun offering free carrier testing through the Decode Duchenne program to asymptomatic females. Historically, the Decode Duchenne program offers genetic testing to persons with a known or suspected diagnosis of Duchenne or Becker muscular dystrophy who are not able to pay for testing. But as of April 1, 2018, we began offering free carrier testing through the Decode program. Applicants who legally reside in the US or Canada, and face any type of financial barriers to obtaining testing may be eligible. More information and our online application can be found at www.parentprojectmd.org/decode.

Additional information on carriers can be found on the PPMD website.  If you, or someone you know, is a carrier of the gene that causes Duchenne muscular dystrophy, please ask them to register/update their information in The Duchenne Registry.  The more information we gather, the better care we can give to the amazing mothers, and all females, in our community.

Decode Duchenne is administered by Parent Project Muscular Dystrophy and The Duchenne Registry. Decode Duchenne is sponsored by Sarepta Therapeutics and PTC Therapeutics.