Upcoming Studies and Trials with more information to come soon..

The Vehicle for Gene Therapy.

4D Molecular Therapeutics-next generation AAV’s designing to circumvent the immune issues and offer more efficient delivery for gene therapy.

Given medicine’s understanding of genetic diseases, and our gene therapy technology, when will cures become a reality? Simply put, once we have highly efficient and customized delivery vehicles (vectors) to deliver the normal genes to the diseased cells in the body, we can turn the hope for cures into a reality. This is the problem that 4DMT is working to solve every day. We are working to create new customized delivery vehicles (vectors) to shuttle genes into the right cells in the body for each disease. This 4DMT proprietary portfolio of vectors includes vectors for the retina (in the back of the eye), for the heart, for muscles, for the lung and many other organs (brain, liver, joints and others). 4DMT and our partners will be able to hand pick a “4D designer vector” for any patient based on the organ (a collection of cells that has a function) that is diseased. These 4DMT vectors are designed to be markedly superior to the current 1st and 2nd generation vectors (see Therapeutic Vector Evolution). We are working to create industry-leading “gold standard” delivery vectors and gene therapy products every single day.

Micro Dystrophin Vector / Gene Therapy

Microdystrophin gene therapy robustly induces the production of a shorter, but functional, version of the dystrophin protein and reduces muscle damage in Duchenne muscular dystrophy (DMD) patients, according to preliminary results of a Phase 1/2 clinical trial.

DMD is a severe type of muscular dystrophy caused by mutations in the dystrophin gene. This leads to the absence of the dystrophin protein, a critical protein involved in the stability and function of muscle fibers. Without the protein, there is progressive muscle degeneration and weakness.

Researchers have been working to develop gene therapies to replace the dystrophin gene, with the goal of protecting the muscle from damage and/or promoting muscle repair.

Among these developing therapies, AAVrh74.MHCK7.micro-Dystrophin — developed by a team at Nationwide Children’s Hospital and licensed by Sarepta Therapeutics — is one of the most advanced.

This therapy uses a virus (the adeno-associated virus, or AAV) to deliver microdystrophin, a shorter version of the dystrophin gene, that contains the minimum amount of information needed to produce a functional dystrophin protein.

It also directs the delivery of the microdystrophin gene specifically to muscle tissue (while avoiding other tissues), in particular the heart muscle, which is crucial for DMD patients, who frequently die from heart disease.

Preclinical studies have shown the therapy induced high levels of microdystrophin protein and restored its levels in skeletal, diaphragm (a major respiratory muscle), and heart muscles


A very exciting reseach study that we are beginning to follow and hope that it will be a CURE!

Researchers have identified a way of changing parts of DNA sequencing to be used as a treatment for genetic diseases. The CRISPR/Cas9 therapy (or clustered regularly interspaced short palindromic repeats) is a new method of genome editing which can be used in the treatment of Duchenne muscular dystrophy.UT Southwestern researcher awarded $250K to study gene editing for Duchenne MD treatment. Find out more. 

CRISPR works by mimicking bacteria’s way of protecting itself when attacked by viral infections by capturing pieces of the virus’s DNA and inserting into its own DNA.When trialed on mouse models of Duchenne muscular dystrophy, CRISPR/Cas9 reported the reversal of some symptoms associated with Duchenne MD.A $2.2-million grant has been awarded to researchers at the Nationwide Children’s Hospital to explore the use of gene therapy in children with Duchenne MD. The CRISPR/Cas9 method will also be researched for the treatment of other genetic diseases such as cystic fibrosis

Eteplirsen Fast Track Approval was granted in September 2016, and it was a very joyous day by all. It made history for our duchenne community being the first drug approved in the U.S. for Duchenne Muscular Dystrophy. Unfortunately this drug now called Exondys 51 is only going to help 13% of the population of duchenne patients and is not a complete cure. We have so much more work to do to save Braedan and all affected with duchenne. We need your help!

Below is a video capturing what happened at the Advisory Committe Meeting on April 25, 2016. It will give you an insight on why it was such an emotional day for us parents attending and watching from home. Please keep us all in your prayers, as we wait for an answer from the FDA on May 26, 2016 as to whether or not they are going to approve Eteplirsen. This drug works, it has been proven in boys, in the science and in our hearts!!!


CureDuchenne has Funded More than $1 Million for Dr. Flanigan’s Duplication 2 Research. Here’s the Latest Research Update

Dr. Kevin Flanigan from Nationwide Children’s Hospital provided an update on his Dup2 research during a CureDuchenne hosted call with families on September 6.

Back in 2010, Dr. Flanigan told me he was working on duplication mutations.  We knew so many families with these rare mutations, and at that time, the excitement seemed to be over common mutations and exon skipping, the duplications seemed to be overlooked.

CureDuchenne started funding Dr. Flanigan’s duplication 2 work in 2011 and we’ve raised more than $1M for this project.  In the past 6 months alone we have raised more than $100K.

We have many people to thank for that. Some of you hosted cookouts, BBQs, marathons, fundraising-sites, emailed your community, posted items on Facebook–all to raise critical funding for Dr. Flanigan’s research. Some of you don’t even have a son with a Dup-2 mutation but instead committed your time and heart to this project for the betterment of the community as a whole.  A very special thank you to the Revell and the Henegar families, please keep their boys, who don’t have a dup2 mutation, in your thoughts and prayers, as they selflessly worked hard to raise the funds for all of the dup2 boys.

We have maintained our commitment to funding Dr. Flanigan’s research. CureDuchenne is currently raising $50,000 for our next installment of his work, which will conduct the toxicology studies necessary to apply for a clinical trial.  CureDuchenne’s research strength is our innovation to vet the science early, de-risk the project and provide leadership so other organizations are able to join in later funding.  We are very pleased to see other non-profit organizations see the great value in this research and have joined in raising funds also.

We are at a critical stage for the research and our commitment has not wavered to ensure that we raise funds for this important work.

Dr. Flanigan provided the following update:  With CureDuchenne’s funding over the last several years, his team has:

  • Created a new mouse model (Dup2) of Duchenne that contains a duplication of exon 2 for the direct testing of exon-skipping therapies

  • Identified a new novel internal ribosome entry site that allows for production of a highly-functional N-truncated dystrophin protein

  • Demonstrated significant exon 2 skipping as well as increased dystrophin production and functional rescue through virally mediated exon 2 skipping

  • Shown that treatment leads to increased production of the truncated dystrophin protein six-month post treatment in Dup2 mouse

  • Has successfully used a viral approach to deliver the exon skipping that differs from gene therapy

  • Established a dose for skipping of exon 2 that helps skeletal, heart and diaphragm. There is no evidence of toxicity.  Early treatment in mice show benefit

  • Had a good pre-IND (Investigational New Drug) meeting with the FDA that is a proposal to do a trial and show pre-clinical data. They will do a toxicology study with outside contract research organization.

  • A plan to begin dosing mice next week for the toxicology study. The toxicology study will take about 3 months.  The contract research organization should have the final report by mid-March.

  • Begun to manufacture the virus to develop clinical support.

  • A plan to start dosing of first patient at the end of the second quarter in 2018.

Q: Can/when will this treat other single exon duplications?

A: The animal model is for single exon duplication but can pave the way for other duplications.  The vector is for exon 2.

Q: Can/when will this treat multiple exon duplications?

A: Skipping a group can be a challenge and will need to see success with single skipping first.  Exon 3-4 duplications, which are actually in frame but can present as Duchenne, might benefit from the IRES.

Q: What will be the age of the trial participants?

A:  They are proposing a safety study to the FDA.  We intend for patients who are walking or pre-walking above the age of 6 months.  We have shown early treatment, prolong effect.

Q: How many patients will be included in the trial?

A:  We are proposing 6 to 12 patients

Q: How many phases of trials will the FDA require?

A:  This will be a Phase 1/2a trial.  We don’t expect a placebo.

Q: What will be the endpoints for the clinical trial?

A: This is primarily a safety study.  Also, efficacy looking for expression of dystrophin.  Outcome measure include muscle biopsy for dystrophin restoration, muscle MRI, 100 Meter Walk and motor function

Q: Because of AAV delivery, will this prohibit patients from future studies?  Or only AAV based therapies?

A: Trial participants will be immunized to AAv9 and precluded with the same vector later.  Note, this is an experimental trial and not an approved drug.  This will prohibit patient’s participation in other clinical trials but should not preclude receiving an approved treatment.

Q:  Are people outside US eligible for clinical trial?

A: It’s not off the table but outside the U.S. does propose challenges.  It is intense the month before and month after the trial.  It includes hospital stay and multiple visits.  Follow up 1 month, 3 month, 6 month 12 month, 18 month and 24 month. Also, if the patient gets sick he will need to be seen at Nationwide right away.  At Nationwide, they work with a lot of International patients and have an international office.

Q:  What is the dosage?

A: They will use an efficacy dose – that to which we expect to be beneficial.  It will be a dose escalation study, but still it is a safety study.  They have a couple papers coming out in the next couple of months.

Debra Miller thanked Dr. Flanigan: We are all grateful that Dr. Flanigan took the road less traveled and addressed the needs of the duplication families.  We look forward to his success in translating this to clinical trials.

“We appreciate CureDuchenne’s unwavering support of our research,” said Dr. Flanigan.

CureDuchenne is grateful for every dollar that all of you have raised, every minute spent on the phone, every Facebook post, bake off and profit-share organized. But most importantly, thank you for putting your story out there to encourage your community to support meaningful research. We know it’s not easy, it can feel frustrating but the success gained so far is because of your commitment to getting this research to trial.

It is imperative that we raise $50,000 over the next few months to maintain the momentum. For more information go:  www.CureDuchenne.org/Flanigan.  Contact Kylee at Kylee@CureDuchenne.org or 949-872-2552 on how you can help or donate today.

Another Family's story with Duchenne MD and their Journey to

Duplication Research at Nationwide



Dr. Kevin Flanigan and his team at the Flanigan Lab at Nationwide Children’s Hospital are hard at work researching duplication mutations. They have created a new mouse model for Duchenne muscular dystrophy with a duplication of exon 2. Their research was recently published in Neuromuscular Disorders (http://www.ncbi.nlm.nih.gov/pubmed/26365037).

“CureDuchenne funded our research early on and was a catalyst that enabled us to move forward with our research on this project,” said Dr. Flanigan, Investigator, Center for Gene Therapy, Nationwide Children’s Hospital. “We are grateful that CureDuchenne funds research to find treatments for all those with Duchenne, including rare mutations.”

Exon duplication mutations are thought to account for up to 11% of all cases of Duchenne muscular dystrophy, and the duplication of exon 2 is thought to be the most common one seen in patients. The absence of a duplicated exon mouse model has hindered approaches to the development of novel exon skipping strategies for these patients.

A new mouse model has been created, that for the first time features an exon duplication model of Duchenne muscular dystrophy. Importantly, this new duplicated exon 2 mouse shows many of the similarities seen in the mdx model and will now allow drug development approaches to advance for patients with duplicated exons at a much faster rate.

Learn more about the science and watch this video that features a family who son could benefit from Dr. Flanigan’s research.

We are very pleased to see Dr. Flanigan’s work progress and proud to have supported his research on duplication and rare mutations from the beginning. We will continue to support his research with the intent to move this forward as quickly as possible. Thank you to the families and other donors who helped fund this important research.

If you would like more information or if you’d like to help support duplication and rare mutation research, please send me your son’s exact mutation:  debra@cureduchenne.org. The more we can rally together, the more we can develop drugs to treat all those will Duchenne.


The first exon duplication mouse model of Duchenne muscular dystrophy: A tool for therapeutic development.

Vulin A1, Wein N1, Simmons TR1, Rutherford AM1, Findlay AR1, Yurkoski JA1, Kaminoh Y1, Flanigan KM2.

Author information


Exon duplication mutations account for up to 11% of all cases of Duchenne muscular dystrophy (DMD), and a duplication of exon 2 is the most common duplication in patients. For use as a platform for testing of duplication-specific therapies, we developed a mouse model that carries a Dmd exon 2 duplication. By using homologous recombination we duplicated exon 2 within intron 2 at a location consistent with a human duplication hotspot. mRNA analysis confirms the inclusion of a duplicated exon 2 in mouse muscle. Dystrophin expression is essentially absent by immunofluorescent and immunoblot analysis, although some muscle specimens show very low-level trace dystrophin expression. Phenotypically, the mouse shows similarities to mdx, the standard laboratory model of DMD. In skeletal muscle, areas of necrosis and phagocytosis are seen at 3 weeks, with central nucleation prominent by four weeks, recapitulating the "crisis" period in mdx. Marked diaphragm fibrosis is noted by 6 months, and remains unchanged at 12 months. Our results show that the Dup2 mouse is both pathologically (in degree and distribution) and physiologically similar to mdx. As it recapitulates the most common single exon duplication found in DMD patients, this new model will be a useful tool to assess the potential of duplicated exon skipping.

Copyright © 2015 Elsevier B.V. All rights reserved.


Duchenne muscular dystrophy; Duplication; Exon skipping; Mouse model



[PubMed - as supplied by publisher]

CureDuchenne’s Funding Bears Fruit with Drisapersen: First-Ever New Drug Application (NDA) Accepted by Food and Drug Administration (FDA) for Duchenne Muscular Dystrophy

Sarepta Therapeutics Separately Completes New Drug Application for Eteplirsen

June 29, 2015 09:41 AM Eastern Daylight Time

NEWPORT BEACH, Calif.--(BUSINESS WIRE)--CureDuchenne today applauded the U.S. Food and Drug Administration (FDA), which took the critical step of accepting the first-ever New Drug Application (NDA) for a possible treatment for those who suffer with Duchenne muscular dystrophy. The FDA said it will accept BioMarin Pharmaceutical’s NDA for drisapersen, the first Duchenne drug ever to reach this stage.

“We are thrilled by the progress of eteplirsen. Reaching the NDA stage of the drug approval process is a significant step toward our ultimate goal of curing this disease. The Duchenne community can draw hope from this latest news, and Sarepta and CureDuchenne will continue to build on this success.”

Separately, Sarepta Therapeutics has announced the completion of an NDA for its drug eteplirsen, also intended to help Duchenne patients.

CureDuchenne, the national nonprofit dedicated to finding a cure for Duchenne muscular dystrophy, was an early funder and supporter of both these promising treatments.

“The Duchenne community is grateful to BioMarin for their dedication in developing this drug, and CureDuchenne is proud to support the first-ever treatment to reach this milestone in the U.S. It could dramatically improve the quality of life for those with Duchenne,” said Debra Miller, co-founder and CEO of CureDuchenne. “We applaud the FDA on this step and are hopeful for an approval later this year.”

In response to the news from Sarepta, Miller said: “We are thrilled by the progress of eteplirsen. Reaching the NDA stage of the drug approval process is a significant step toward our ultimate goal of curing this disease. The Duchenne community can draw hope from this latest news, and Sarepta and CureDuchenne will continue to build on this success.”

Duchenne muscular dystrophy, an inherited genetic disease with no cure and no treatment up to now, causes progressive muscle degeneration, leaving patients wheelchair-bound by their mid-teens. Almost all of them are boys and young men. Most do not survive their mid-20s.

Drisapersen was developed by Prosensa, which was recently acquired by BioMarin. Both it and Sarepta’s drug are amenable to exon 51 skipping – essentially, ignoring mutations in a patient’s genome that prevent the body from producing a vital protein called dystrophin. Lack of dystrophin is what causes muscle deterioration. Exon skipping alters the splicing pattern of the Duchenne mutation, which encourages the cells to produce new dystrophin, thereby maintaining muscle strength. Exon skipping is a mutation-specific treatment, meaning that it is a form of personalized medicine. This drug, therefore, would positively affect only about 13 percent of those with Duchenne muscular dystrophy.

”We believe strongly that the science behind this research will one day be able to help a larger percentage of those with Duchenne. We will continue to support their efforts in the hopes that promising treatments can become a promise for a cure,” said Miller.

CureDuchenne was founded in 2003 with a focus on saving the lives of those with Duchenne muscular dystrophy, a disease that affects more than 300,000 boys worldwide. With support from CureDuchenne, seven research projects have advanced to human clinical trials, and three of these pharmaceutical treatments could be approved by the FDA within the next year. These treatments may lessen the effects of the disease for those with certain mutations of Duchenne, but there is still much work to be done to find a cure. For more information, please visit CureDuchenne.org and follow us on FacebookTwitter and YouTube.

BioMarin Completes Rolling NDA Submission to FDA for Drisapersen for Treatment of Duchenne Muscular Dystrophy Amenable to Exon 51 Skipping

SAN RAFAEL, Calif., April 27, 2015 (GLOBE NEWSWIRE) -- BioMarin Pharmaceutical Inc. (Nasdaq:BMRN) today announced completion of the rolling submission of a New Drug Application (NDA) to the United States Food and Drug Administration (FDA) for drisapersen, an investigational exon-skipping drug candidate for the treatment of the largest genetically defined subset of Duchenne muscular dystrophy (DMD). DMD is the most common fatal genetic disorder diagnosed in childhood, affecting approximately 1 in every 3,500 live male births with about 20,000 new cases diagnosed globally each year. Drisapersen induces the skipping of dystrophin exon 51, potentially providing a therapeutic benefit to DMD patients for whom skipping of exon 51 restores the proper dystrophin reading frame, corresponding to approximately 13% of DMD patients. The company intends to also submit an application for registration in the European Union in summer 2015.

"We believe drisapersen may offer a meaningful benefit to boys living with DMD whose mutations are amenable to exon 51 skipping. The totality of data on drisapersen contains three randomized, placebo-controlled, efficacy trials and two long term extension studies, which include some boys treated for approximately 3.4 years," said Camilla V. Simpson, Global Head of Regulatory Affairs, Pharmacovigilance. "With this application, BioMarin continues in its long-standing tradition of developing important therapies for those who are most in need. The submission of the NDA represents a significant milestone for BioMarin, and we appreciate the strong, collaborative effort of many hard working employees, investigators, patients and their families. We look forward to working with the U.S. Regulatory Authorities to thoroughly understand the data generated for this heterogenous and critically ill patient population and hopefully to bring this treatment to patients expeditiously." 

Drisapersen has been granted Orphan and Fast Track status, as well as Breakthrough Therapy designation by the FDA.

DMD is caused by a mutation in the gene that encodes for dystrophin, a protein that is important in connecting the cytoskeleton of muscle fibers to the extracellular matrix. Its deficiency in DMD leads to progressive muscle weakness, loss of ambulation in early adolescence, and typically death due to pulmonary or cardiac insufficiency in the late twenties. Because the Duchenne gene is found on the X-chromosome, it primarily affects boys; however, it occurs across all races and cultures. There is currently no approved therapy in the United States for DMD.

"This is a first for the Duchenne community, and we are filled with hope that there could be a treatment for Duchenne in the United States," said Debra Miller, co-founder and CEO of CureDuchenne. "CureDuchenne has been supporting the development of drisapersen for more than a decade, and we are delighted that BioMarin has reached this important stage. We salute the researchers who have been working so hard, and we share their determination to find a cure for Duchenne."

About Drisapersen

Duchenne muscular dystrophy (DMD) is a severely debilitating childhood neuromuscular disease that affects up to 1 in 3,500 live male births. This rare disease is caused by mutations in the dystrophin gene, resulting in the absence or defect of the dystrophin protein. As a result, patients suffer from progressive loss of muscle strength, often rendering them wheelchair-bound before the age of 12 years. Respiratory and cardiac muscle can also be affected by the disease and most patients die in early adulthood due to respiratory and cardiac failure.

About Exon Skipping

Exons are the parts of a gene that contain the instructions for generating a protein. In DMD, mutations in the dystrophin gene lead to the absence of dystrophin protein, resulting in the most severe form of muscular dystrophy. In applicable cases, skipping an exon near the mutation allows for the production of a truncated but functional dystrophin protein.

About BioMarin

BioMarin develops and commercializes innovative biopharmaceuticals for serious diseases and medical conditions. The company's product portfolio comprises five approved products and multiple clinical and pre-clinical product candidates. Approved products include Vimizim® (elosulfase alfa) for MPS IVA, a product wholly developed and commercialized by BioMarin; Naglazyme® (galsulfase) for MPS VI, a product wholly developed and commercialized by BioMarin; Aldurazyme® (laronidase) for MPS I, a product which BioMarin developed through a 50/50 joint venture with Genzyme Corporation; Kuvan® (sapropterin dihydrochloride) Powder for Oral Solution and Tablets, for phenylketonuria (PKU), developed in partnership with Merck Serono, a division of Merck KGaA of Darmstadt, Germany and Firdapse® (amifampridine), which has been approved by the European Commission for the treatment of Lambert Eaton Myasthenic Syndrome (LEMS). Product candidates include drisapersen, an exon skipping oligonucleotide, for which a marketing application has been submitted to FDA for the treatment of patients with Duchenne muscular dystrophy (DMD) with mutations in the dystrophin gene that are amenable to treatment with exon 51 skipping, pegvaliase (PEGylated recombinant phenylalanine ammonia lyase, formerly referred to as BMN 165 or PEG PAL), which is currently in Phase 3 clinical development for the treatment of PKU, talazoparib (formerly referred to as BMN 673), a poly ADP-ribose polymerase (PARP) inhibitor, which is currently in Phase 3 clinical development for the treatment of germline BRCA breast cancer, reveglucosidase alfa (formerly referred to as BMN 701), a novel fusion protein of insulin-like growth factor 2 and acid alpha glucosidase (IGF2-GAA), which is currently in Phase 3 clinical development for the treatment of Pompe disease, BMN 111, a modified C-natriuretic peptide, which is currently in Phase 2 clinical development for the treatment of achondroplasia, BMN 044, BMN 045 and BMN 053, exon skipping oligonucleotides, which are currently in Phase 2 clinical development for the treatment of Duchenne muscular dystrophy (exons 44, 45 and 53), cerliponase alfa (formerly referred to as BMN 190), a recombinant human tripeptidyl peptidase-1 (rhTPP1) for the treatment of CLN2 disorder, a form of Batten disease, which is currently in Phase 1, BMN 270, an AAV-factor VIII vector, for the treatment of hemophilia A and BMN 250, a novel fusion of alpha-N-acetyglucosaminidase (NAGLU) with a peptide derived from insulin-like growth factor 2 (IGF2), for the treatment of MPS IIIB.

For additional information, please visit www.BMRN.com. Information on BioMarin's website is not incorporated by reference into this press release.

Forward-Looking Statement

This press release contains forward-looking statements about the business prospects of BioMarin Pharmaceutical Inc., including, without limitation, statements about: expectations regarding the rolling NDA submission for drisapersen with the FDA and the pending submission to the European Medicines Agency (EMA); the potential outcome of the review of such filings; and the possible approval of such product candidates. These forward-looking statements are predictions and involve risks and uncertainties such that actual results may differ materially from these statements. These risks and uncertainties include, among others: results and timing of current and planned clinical trials of its product candidates; the content and timing of decisions by the FDA, the EMA and other regulatory authorities concerning its product candidates; and those factors detailed in BioMarin's filings with the Securities and Exchange Commission, including, without limitation, the factors contained under the caption "Risk Factors" in BioMarin's 2014 Annual Report on Form 10-K, as amended, and the factors contained in BioMarin's reports on Form 8-K. Stockholders are urged not to place undue reliance on forward-looking statements, which speak only as of the date hereof. BioMarin is under no obligation, and expressly disclaims any obligation to update or alter any forward-looking statement, whether as a result of new information, future events or otherwise.

BioMarin®, Naglazyme®, Kuvan®, Firdapse® and VIMIZIM® are registered trademarks of BioMarin Pharmaceutical Inc.

Aldurazyme® is a registered trademark of BioMarin/Genzyme LLC.

"We are excited and very proud to help sponsor this Duplication Trial

that is taking place so close to home. "

This trial will not only help Braedan but also many other boys with the much

Rarer Duplication Mutation.  Read below..

There are many exciting studies and trials that are happening now and that are on the horizon.  The below mentioned study is one that we have helped fund. It is a duplication trial that is happening in Columbus at the Nationwide Childrens Hospital. We funded over $40,000 towards this trial through the help of Cure Duchenne.

We are very confident in Dr. Kevin Flanigan and the studies that take place at Nationwide. We believe that this study will be a great success and are hopeful that it will help all the boys with the duplication gene and pave the way for others as well.


CureDuchenne, a national nonprofit that raises awareness and funds research to find a cure for Duchenne muscular dystrophy, announced today that they are sponsoring a $710,000 research project with Kevin Flanigan, M.D., principal investigator at the Center for Gene Therapy at Nationwide Children’s Hospital in Columbus, Ohio, that focuses on the development of a novel therapy for duplication mutations for Duchenne muscular dystrophy. The project will fund the production of the drug substance (an adeno-associated virus AAV9.U7) that will be used in the IND-enabling toxicology/biodistribution studies.

 Dr. Flanigan’s research focuses on exon skipping for duplication mutations. Duchenne is a progressive muscle-wasting disease that is estimated to affect 1 in 3,500 boys. Muscle degeneration is due to an absence of a protein in the muscle called dystrophin. Dystrophin is a large gene with 79 exons. The exons get spliced together to form a final blueprint. In Duchenne patients, the blueprint cannot be read from start to finish so the body can’t make the protein. Exon skipping alters the splicing pattern in a gene containing a Duchenne mutation in order to restore the reading frame. This would give a boy with Duchenne a shorter, but still functional dystrophin protein. The goal is to take out the duplicated exon and make it normal, which is called a wild type dystrophin, to restore a normal blueprint.

 Dr. Flanigan’s research focuses on the clinical development of an U7snRNA vector for exon 2 skipping; therapy for exon 2 duplications and the five prime mutations on the Duchenne muscular dystrophy gene. Dr. Flanigan’s lab has identified a novel element in the dystrophin gene that may allow the rescue of mutations that are way up in front of the gene – the 5’ region of the gene. This element, called the Internal Ribosome Entry Site (IRES), allows translation of a protein from a starting site within exon 6.  It gives a large therapeutic window for the idea of skipping exon 2.  This is because skipping of only one copy of exon 2 would give a normal gene message, and complete skipping of exon 2 would activate the IRES and result in the translation of a highly functional shorter version of the protein.  These results not only provide a great deal of confidence in the usefulness of this vector for patients with duplications of exon 2, but also provide a potential treatment for any patients with mutations within the first 5 exons of the gene.

Results of Dr. Flanigan’s study were recently published in the journal Nature Medicine, and was supported by funding from CureDuchenne. In 2011, CureDuchenne provided the funding for Dr. Flanigan to create a new Duchenne mouse model with a duplication mutation of exon 2, providing the first animal model in which to directly experiment with exon skipping for duplication mutations. These results provide Dr. Flanigan’s lab with a pathway forward to treat patients with a duplication of exon 2, and also patients with mutations within the first five exons of the gene.

“CureDuchenne recognized early on the importance of our research focused on rare and duplication mutations and we wouldn’t be here today without their support,” said Dr. Kevin Flanigan. “CureDuchenne supported the development of the mouse model and the personnel to work on this research. CureDuchenne plays a vital role in funding early phase research projects to help accelerate their development.” 

 This new research project continues CureDuchenne’s support of Dr. Flanigan’s research and is part of CureDuchenne’s comprehensive strategy offunding Duchenne research that could potentially lead to treatments and a cure for Duchenne. CureDuchenne has funded all types of Duchenne research including exon skipping, rare mutations, stop codon, anti-fibrotic therapies, utrophin upregulation and anti-inflammatory.

Boys with Duchenne are usually diagnosed by age 5, in a wheelchair by 12 and most don’t survive their mid-20s. There is currently no cure for Duchenne.

“Dr. Flanigan’s research expands our understanding of the genetic underpinnings of Duchenne and will help uncover new paths toward a cure,” said Debra Miller, CEO and founder of CureDuchenne. “We want a cure for all affected by the disease, and that is why we have supported all duplication and rare mutations. CureDuchenne is pleased to see Dr. Flanigan’s work progress and is proud to continue to support his important work. We encourage Duchenne families and other donors to help us fund this important research.”

The link below will take you to all trials that are currently taking place. 


Please watch the following videos below to learn more about the research going on from Nationwide by Dr. Flanigan.