Many couples in which one partner has myotonic dystrophy want to have children. There is a study that looks at pre-Implant diagnosis here the threat of the disease is eliminated. This is a good route for many couples. If universal education were available it may be possible to greatly reduce this disease.
Preimplant-Study-Pregnancy-Myotonic-Dystrophy
Conclusion: Patients with myotonic dystrophy may have an increased risk of thyroid cancer and choroidal melanoma
and, possibly, testicular and prostate cancers.
This company is working on a potential approach to knock down myotonic dystrophy, Here is their letter to teh community of DMD and DM1
Audentes-Therapeutics-community-letterby Ana María Rodríguez, Ph.d., Baylor College of Medicine
Myotonic dystrophy type 1 (DM1) is the most common adult-onset muscular dystrophy that affects multiple organ systems. People with this condition develop progressive muscle wasting and weakness in their lower legs, hands, neck and face. Their muscles feel stiff and tight, causing them to be slow to relax certain muscles and therefore have difficulty releasing the hand from a handshake or a doorknob. In addition, people with this condition may have fatigue, muscle pain, difficulty swallowing, cataracts, irregularities in their heartbeat and respiratory complications. In his laboratory at Baylor College of Medicine, Dr. Thomas A. Cooper is leading the way to better understand this rare but devastating condition.
“Muscle wasting in this disease, which happens over decades, is responsible for the death of 60 percent of the patients,” said Cooper, who is professor of pathology and immunology, of molecular and cellular biology and of molecular physiology and biophysics at Baylor College of Medicine. “In this study we wanted to develop a novel model of the disease that would allow us to study muscle wasting in more detail.”
DM1 is caused by a striking expansion of three-letter repeats (CTG) in the DMPK gene. While the unaffected population carries 5 to 37 repeats, people with the condition have 50 to 3000 repeats. The RNA transcripts containing the CTG repeat expansion accumulate in the cell nucleus. This disturbs the normal cellular processing and distribution of molecules, such as muscleblind-like (MBNL) proteins, and induces up-regulation of others, such as the CELF1 protein. These alterations result in abnormal alternative splicing, which is thought to play a central role in the development of DM1. However, how these changes triggered by the expansion of the CTG repeat lead to muscle wasting still is not completely understood.
“We think that the current animal models of DM1 do not provide researchers with a complete and practical tool to investigate the mechanisms involved in muscle loss,” said Dr. Ginny Morriss, postdoctoral associate in the Cooper lab and the first author of this work. “This disease has many different components. Current animal models have some of the molecular components, but the physiological components, what’s happening to the tissue, are mostly missing. We wanted to develop a mouse modelof DM1 that clearly showed muscle loss and to implement a strategy that would allow us to study the pathways involved in muscle wasting.”
A mouse model of reversible DM1
The researchers genetically engineered a skeletal muscle-specific mouse model of DM1 that allowed them to induce the development of the disease at will. When induced, the mice expressed 960 CUG repeats of a particular region of the human DMPK gene and the RNA transcripts containing the CUG repeat expansion accumulated inside the cell nucleus triggering the chain of events that resulted in progressive muscle wasting. When the researchers ‘turned off’ the expression of the 960 CUG repeats, RNA accumulation and muscle loss progressively reverted.
In this model, the researchers saw alternative splicing that was consistent with findings in previous studies that correlated it with muscle weakness. They also validated signaling pathway changes that had been previously found by others. Importantly, they saw signaling pathway changes that had not been described before. These new changes stratified with how severe muscle wasting was in the mice, showing a clear association between specific signaling pathways and muscle loss.
“We validated the upregulation of the activity of protein AMPK-alpha, which had been shown previously by another group in another model. AMPK-alpha regulates the way the muscles metabolize and function,” Morriss said. “One of the new changes we discovered in our model was the dramatic reduction of signaling activity mediated by PDGFR-beta, which is involved in energy metabolism pathways.”
In addition, Cooper, Morriss and their colleagues found a connection with the human condition. They analyzed human tissue samples from patients and unaffected individuals and found in the patients the same signaling pathway changes they had found in their mouse model.
“The field has been focusing on alternative splicing. But, one of the things our findings tell us is that, although many of the characteristics of the disease result from alternative splicing defects, in addition there are other mechanisms at play and therefore other potential targets to treat this disease. There is more going on here than just alternative splicing,” said Cooper, who also is the S. Donald Greenberg and R. Clarence and Irene H. Fulbright Professor and a member of the Dan L Duncan Comprehensive Cancer Center at Baylor.
“Now we have a mouse model in which we can test mechanisms involved in the disease. Because we made our model reversible, we can use it to test hypotheses about how the repeats cause the characteristics of the disease. We can systematically test each one of those hypothesis independently in our model blocking each signaling event specifically and determining how much that affects the disease. We can in this way determine how much each of the disease components, signaling pathways and alternative splicing, contribute to the disease,” Cooper said.
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We were saddened to hear of the Death of Kayla who was brave and choose to be the face of this disease. She warmed everyones heart, now the hearts are a little colder.
KAYLA MICHELE VITTEK
July 28, 2005 – April 9, 2019 Resident of Santa Cruz, CA
Kayla Michele Vittek, a beautiful, bright and deeply cherished 13 year-old girl, died peacefully in her sleep in the early morning hours of Tuesday, April 9, 2019. Kayla lived with her mother, Lisa Michele Harvey-Duren, her step-dad Paul Duren and her ten year-old sister in Santa Cruz.
Kayla embraced those that she trusted with her whole heart. For those special people that she let in, she showed a side of herself that not everyone got to see. She had a great sense of humor, she was gentle, kind, empathetic and she genuinely loved life. Kayla loved showing her affection by planting gentle kisses on her loved ones faces. She also gave the most amazing hugs. She loved to dance and adored music from an early age. She especially loved the music of Eric Hutchinson and wouldn’t go to sleep at night until we played his songs. Kayla has blessed our lives and her spirit will live on forever in our hearts.
Kayla was born at Sutter Memorial Hospital in Sacramento, California in 2005. She began her early intervention and education in Rocklin, CA, and transferred to the Soquel Union School District in Santa Cruz County in Kindergarten in 2011. She attended Soquel Elementary School, followed by almost three years at New Brighton Middle School, where she excelled academically thanks to the devoted care of her academic aides and teachers. Despite physical challenges, speaking problems due to the disease and hypersensitivity to sounds, she made the honor roll at New Brighton every semester and was just two month away from graduation and advancement into high school. Kayla loved to read and especially loved science and humanities. Her unexpected success in all facets of her life was miraculous considering the severity of her disease. She was not expected to survive her first year, nor to ever walk or talk. During her final year at New Brighton, she was invited to participate in the student council.
Despite her difficulties with mobility, Kayla loved sports, beginning at age three with horseback riding (hippotherapy) at Ride-To-Walk, and continuing with baseball and soccer from age 7. Kayla played baseball in the challenger league with the Angels, a team made up of individuals living with disabilities. Kayla’s father Jeff loved playing baseball with Kayla on their visits together. In their first game of this season, the weekend after Kayla passed, the Angels had a moment of silence in memory of Kayla and then played her walk-up music, Brave by Sara Bareilles. Kayla participated in Ride-A-Wave and Day at the Beach over the past 6 years. She participated in Day of Discovery snorkeling program at Monterey Bay Aquarium for the past few years. She was a recipient of Make-a-Wish Foundation gift to travel to Hawaii with her family in 2016. Kayla’s favorite event every year was by far MDA camp for kids living with muscular dystrophy. Kayla attended this camp since the age of 6 and with her very special friend Kali for many years and then this past year with Kali, Zoe and Cambry who all live with DM1.
Kayla faced a life-long struggle with congenital myotonic dystrophy (DM1), the most prevalent form of muscular dystrophy. Under the care of her mother and her medical team at Lucile Packard Children’s Hospital at Stanford, led by the chair of the Neuromuscular Department, Dr. John W. Day, MD, PhD., Kayla flourished. She became known throughout the global community of DM patients and caregivers through her blog, www.cureforkayla.com as many newly diagnosed patients would find Kayla’s story of hope and would reach out to us. Because of Kayla’s struggle, her mother Lisa helped to found and became the founding executive director of the Myotonic Dystrophy Foundation (MDF), which funds research into this genetic disorder and provides support to families living with this disease.
Kayla appeared regularly in news stories and on television over the past 13 years and she and her mother were spokespeople and strong advocates for DM. Kayla was named the Youth Ambassador for Easterseals Superior California in 2006 and her story was aired on the Sacramento news. Kayla’s story was updated every year on the Sacramento Muscular Dystrophy Association (MDA) Jerry Lewis Telethon from 2006 to 2008 and she was the 2009 face of myotonic dystrophy on the National MDA Jerry Lewis Telethon where she appeared with her father Jeff and her mother Lisa. In 2014 Kayla and Lisa testified in Washington D.C. in a Congressional hearing in support of the reauthorization of the MD-CARE Act which was eventually granted. Kayla participated in a longitudinal research study of congenital myotonic dystrophy patients every year for the last five consecutive years at the University of Utah. Kayla also participated in research at Stanford University. Kayla was about to begin a clinical trial at Stanford for a new drug that improves executive functioning. These are just a few of her accomplishments in her short life.
Kayla was predeceased by Robert and Patricia Vittek, paternal grandparents; June Hull Ferguson, great aunt; and Stephen Harvey, maternal uncle. She is survived by her other family members, who mourn her loss and cherish her memory: Lisa Harvey-Duren, mother; Jeff Vittek, father; Paul Duren, step-father, and her sister; Jane Hull Harvey and Rev. Pharis Harvey, maternal grandparents, Dr. Kathryn Harvey, maternal aunt, Christopher Harvey and Roxanne Ward Zaghab, maternal uncle and aunt; Mitch Vittek, paternal uncle; Rich and Sue Vittek, paternal uncle and aunt; Daniel Harvey, Noelle Pruett, Maya Pruett, Kathryn Harvey, Brenan Batten, Logan Batten, Andie Lee Batten, maternal cousins; Shelby Vittek, Lindsay Vittek and Sarah Hollenback, paternal cousins.
There will be a Celebration of Life of Kayla Michele Vittek at Aptos United Methodist Church on Saturday, April 27, 2019 at 11:00 a.m.. Please RSVP for the event or the live stream.
In lieu of flowers, please consider making a donation to either the Muscular Dystrophy Association or the Myotonic Dystrophy Foundationand note in the memo: Kayla Vittek memorial fund.
Please leave messages for Kayla’s family in the comments below.
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