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.