Follistatin Gene Therapy

Drs. Jerry Mendell and Brian Kaspar are investigators in the follistatin gene therapy trial for inclusion-body myositis patients now underway at Nationwide Children's Hospital.

Aisha Morrow, TMA:  Drs. Jerry Mendell and Brian Kaspar are researchers in the follistatin gene therapy trial for inclusion-body myositis patients now underway at Nationwide Children's Hospital. Several IBM patients have been treated, and the trial will continue with a slightly higher dose for the IBM patients. This historic treatment, pioneered in both mice and non-human primates with simulated sIBM, has prompted many questions from IBM patients. Both researchers answer questions today, and we welcome them. If you are joining us after the start of the discussion, please read the first group of answers before leaving your question to avoid duplication.Drs. Mendell and Kaspar, thanks for being with us today.

Drs. Mendell and Kasper:  Thank you for having us, we are happy to answer as many questions. To clarify, we will be injecting other iBM patients with a higher dose in both legs.

TMA Member:  What are the side effects of follistatin?

Drs. Mendell and Kasper:  To date, we have not seen any side effects or adverse events related to the gene therapy or follistatin expression. This means the trial has been safe and well tolerated to date.

TMA Member:  I am a sixty-six year old male diagnosed with IBM twelve years ago. If your follistatin gene trial results continue to be positive can you give us an expectation when the treatment will be available to other IBM patients?

Drs. Mendell and Kasper:  Right now we're in the middle of the trial, and so far safe and well tolerated. We will have to take the data we collect safety and efficacy data to the Food and Drug Administration and move this forward as quickly and safely as possible. As we don't have the trial Phase I completed it is hard to set a date or timing, but we will move as quickly and safely as possible to bring this forward if it is deemed safe and effective.

TMA Member:  I know this doesn't bear directly on the subject but can you comment on any possible efficacy of IV IG treatment for IBM?

Drs. Mendell and Kasper:   Through clinical trials there does not appear to be any benefit of IVIG treatment for IBM patients.

TMA Member:  How long did it take the Becker study group to show improvement?

Drs. Mendell and Kasper:  The patients are still under study and we are collecting additional information. The important point is that the injection has been well tolerated and there may be signs of benefit, but too early to put a timepoint for efficacy.

TMA Member:  Will the trial have injections in the hands in the future?

Drs. Mendell and Kasper:  Our ultimate goal is to target many muscle groups, but this is the first stage of trials at this time. We are pushing more systemic muscle studies currently, but those new studies are in earlier stages.

TMA Member:  What is the criteria used for acceptance into the study once a person has been tested? Is age a factor?

Drs. Mendell and Kasper:  Age is not a factor. Patients at this time must be ambulatory, and also not have high levels of pre-existing immunity to AAV. If this trial is effective, we would request FDA to go back and test the therapy in non-ambulatory patients.

TMA Member:  Your research looks encouraging. Is there anything we can do to facilitate your ability to bring this treatment to us sooner? I'm referring to political activities by us on your behalf?

Drs. Mendell and Kasper:  Thank you very much, we are excited about our research and moving this into the first human clinical trials for IBM patients. We appreciate your willingness to help us. We are working very hard on all of the regulatory process, receiving orphan drug designation status, and moving as fast as we can. What is limiting is funding for running the actual clinical trial.

TMA Member:  Assuming gene therapy treatment is approved for IBM, will the cost be covered by Medicare?

Drs. Mendell and Kasper:  We have to get this approved by FDA as the first hurdle. The clinical trial does not cost the patient or Medicare any money, We have to fund this via grants/foundations. If a drug is approved and there are no other therapies available, Medicare would likely cover the costs, but again, it has to be an approved drug.

TMA Member:  If new muscle tissue is formed as a result of this treatment, will they be subject to the same deterioration process as found in sIBM?

Drs. Mendell and Kasper:  This is a very good questions, and the truth is we don't know. What we do know is that follistatin appears to suppress the inflammation found in muscle tissue and we are encouraged by that.

TMA Member:  Dear Drs Mendall and Kasper,Could this gene therapy trial be conducted in Australia, also how are the patients treated for this therapy? I was diagnosed with IBM several years ago.

Drs. Mendell and Kasper:  The first human trial is currently only in the US, and only at one site, Nationwide Children's Hospital. We accept patients outside the country, but for a trial like this, would have to stay for at least 6 months. In the future, if successful, we of course would open to many sites.

TMA Member:  Are you enrolling new IBM patients into the trial?

Drs. Mendell and Kasper:  yes, we continue to screen patients for enrollment. The Children's Hospital Gene Therapy website has contact information.

TMA Member:  Have the next six participants been chosen for the study?

Drs. Mendell and Kasper:  No, we are still screening patients. We would be very happy to be able to screen anyone interested.

TMA Member:  My name is Gary and I'm from Oshkosh, Wisconsin. I was diagnosed with IBM after a thigh muscle biopsy in January of 2008 and will be 60 in just over a week. I am getting progressively weaker but am extremely excited about the progress of this trial. Can you give us some idea of the possible expediency we may expect/hope for with further positive results from your wonderful efforts with Follistatin in the viral conduit? Secondly, do you believe this type of treatment can potentially help us repair/overcome some prior muscle weakening? Thank you very much. I will be on this call.

Drs. Mendell and Kasper:  Hello Gary, First age has nothing to do with eligibility and if interested, please contact us for screening for the clinical trial. We are working with the FDA and oversight committees that are checking for safety in the testing, and if this work is positive, will promise to move the therapy forward to more patients and trials as mandated by the FDA to move this to an approved drug.

TMA Member:  What were the signs of benefit?

Drs. Mendell and Kasper:  Safety is the primary goal of this first trial, We are collecting many data points on leg function (walking, climbing stairs, force measurements, as well as biopsy evaluation). With trials, we are collecting as much data as possible and can only share definitive results at the end of the first trial. We can state that the injections have been safe and well tolerated to date.

TMA Member:  After the FDA approval what would the next study look like; number of patients, length of time, degree of IBM effects?

Drs. Mendell and Kasper:  This is a difficult question and really is dictated by safety and the results of the first study. We are thinking of all scenarios, but it's too early to have this fully mapped out at this time. Something we're working on though.

TMA Member:  Is the Follistatin only effective on the muscles that are injected?

Drs. Mendell and Kasper:  Our animal studies demonstrated that muscle that were injected received the greatest effect, but other muscles demonstrated strength and size improvements. These are the same things we are currently testing in our clinical trial.

TMA Member:  My neurologist said this trial is mainly to determine safety dosages .Would you care to comment.

Drs. Mendell and Kasper:  Safety is the primary outcome for this trial, but we are also collecting a great deal of functional measurements. We do think early treatment would have greater effects on muscles.

TMA Member:  How do you determine improved muscle strength?

Drs. Mendell and Kasper:  We have a number of measurements:strength testing, 6 minute walk test, stair climbing, getting up from chair, muscle biopsies. A great deal of data is being collected!

TMA Member:  If successful, would this treatment benefit people that have had IBM for many years with a lot of muscle wasting?

Drs. Mendell and Kasper:  Hi Mike, We actually don't know the answer to this, but is something that we will have to explore in future trials. We do know in mouse studies that we can treat at later stages and see some benefits, but again the greatest benefits are when treated early. We will test this exact question in patients and we can hope that there will be benefit.

TMA Member:  Do you inject the treatment in the muscles you want to improve?

Drs. Mendell and Kasper:  Yes, Dr. Mendell has designed the trial to treat the most affected muscle group (quads) for the first trials. Injected muscles in our pre-clinical studies showed the greatest benefits.

TMA Member:  Will there be any investment opportunities at Milo Biotech (i.e. IPO's)?

Drs. Mendell and Kasper:  Milo Biotech is supporting the advancement of this therapy if it is successful, making a path towards getting this fully approved if we are successful in the human studies. Currently the company is private, and to our knowledge is not planning on an IPO, but may likely raise funds in the near future to advance the product.

TMA Member:  Will the treatment if it works be made available for PM and DM patients?

Drs. Mendell and Kasper:  This is likely a good question for the FDA, given that PM and DM have currently other treatment options.

TMA Member:  Will IBM patients be given a stronger dose in a second phase of the trials? If so, when will that happen and will you be recruiting new subjects?

Drs. Mendell and Kasper:  yes on the higher dose, we're moving as quickly as the regulatory bodies will allow us, Again, our goal is to run a safe and best chance for success study, And in new studies, (higher doses) will be recruiting new subjects.

TMA Member:  Your IBM trial concentrates on the leg muscles. Is there a possibility for adaptation of your trials to other involved muscle groups, especially the arms and hands?

Drs. Mendell and Kasper:  Likely in future studies, if it works in the leg muscles, we can certainly discuss with the FDA.

TMA Member:  Do you have any comment whether or not the Affordable Care Act will have an effect on this clinical trial?

Drs. Mendell and Kasper:  If FDA and Medicare approve it, it appears that it would be covered by the Affordable Care Act. These are being figured out on Capital Hill! and beyond Dr. Mendell and Dr. Kaspar's political knowledge.

TMA Member:  How many people are on the waiting list for this study? I'm on the list--how do you select patients from this waiting list?

Drs. Mendell and Kasper:  Please contact us as you may need to be re-checked and we are also adding new patients to the study list. There are a multitude of enrollment criteria set by FDA.

TMA Member:  When do you expect to be able to share the test results with us?

Drs. Mendell and Kasper:  We expect to have a reasonable idea of the results in the next 6 months. However, we are pleased to state that the therapy has been safe and well tolerated to date.

TMA Member:  How do I become part of this study?

Drs. Mendell and Kasper:  Please contact us on our website, at The Center for Gene Therapy, at Nationwide Children's and likely you would be evaluated here by our team.

TMA Member:  Are there similar studies being done internationally?

Drs. Mendell and Kasper:  The AAV Follistatin is currently only being performed by us.

TMA Member:  What is follistatin?

Drs. Mendell and Kasper:  Follistatin is a protein that blocks another protein called myostatin that is a negative regulator of muscle growth. Simply put, Follistatin causes muscles to get larger and stronger. It also has anti-inflammatory effects, which we believe is advantageous for IBM.

TMA Member:  Have the new patients been selected?

Drs. Mendell and Kasper:  No, not at this time, We are very interested in screening additional patients.

TMA Member:  Are McDonalds and KFC experimenting with this process to create larger livestock?

Drs. Mendell and Kasper:  Interesting question, Not likely McD's or KFC, but the concept is out there and in fact there are transgenic cows that are myostatin depleted, There are also other companies exploring this concept.

TMA Member:  I was one of the first thirty to be tested for this study. Will I have to be retested for the study seeing that the original testing took place over two years ago?

Drs. Mendell and Kasper:  Yes, we would have to evaluate you. We appreciate your efforts.

TMA Member:  Hi Doctors:Has gender any bearing on the results achieved to date?

Drs. Mendell and Kasper:  No, there has been no influence of gender on any safety or data collected to date.

Aisha Morrow, TMA:  Well, that's it for today's discussion. Thanks to all the members who participated today. And a special thanks to Drs. Jerry Mendell and Brian Kasper again for being with us and graciously spending the time to answer your questions.

Drs. Mendell and Kasper:  Thank you very much and we hope our answers have been helpful. If there are patients interested in participating please email: This e-mail address is being protected from spambots. You need JavaScript enabled to view it .  Dr. Mendell, Dr. Kaspar and our team will remain committed to working hard on this trial and we look forward to keeping everyone updated. Our best.






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