Will Rosellini

At the start of each year, we propose a number of research focus areas and then work through a process to determine which disease state to focus our preclinical activities on…so our first year it was chronic pain and tinnitus, the second year urinary incontinence, the third year was motor deficit after stroke and this year we have chosen motor deficit from Parkinson’s disease.  We advance candidates through 4 essential phases, hypothesis, preclinical evaluation, clinical evaluation and then commercialization.  To date, we have shown that our tinnitus therapy is through the 3rd hurdle of clinical evaluation, but still needs support from NIH and investors to get into commercialization.  We are making some progress on this by establishing the regulatory pathway needed for a European and US approval.  This process is a long one, but one in which we are familar with.  Right now, both FDA and BSI are evaluating our data to determine the amount of evidence we will need to submit to receive approval.   Once we get this information we will collect that data and make our submissions for commercial approvals.

In the interim, we also hope to fund a small pilot study to evaluate our targeted plasticity therapy for patients that have sufferered a stroke.  We have published some promising preclinical data in rats and now have a very complete set of preclinical data to support our first clinical study.  We hope to start this sometime this year (of course depending on funding).

Given our expertise in sensory and motor deficits, we hope to begin studying motor deficit from Parkinson’s this year in rat studies.   I provide a brief overview of where we are with this disorder using deep brain stimulation…hopefully we will get a strong signal in PD rats in 2012 and begin clinical trials in 2013.

Deep brain stimulation has been proven to markedly improve the motor functions in patients suffering from severe Parkinson’s disease.  How does it work? Stimulation of various neurons of the central nervous system is known as deep brain stimulation (DBS). DBS can alter the electrical activities of different parts of the brain via a controlled mechanism; accordingly, it is utilized in conjunction with neuroimaging studies to map the various mechanisms of brain functions. A basic DBS system comprises 2 main components: 1- Special electrodes that are implanted in special parts of the brain in order to conduct stimulation electrical impulses to the brain cells. 2- An electrical pulse generator (PG) which creates the stimulation impulses that are conducted to the electrodes implanted on the brain. What are the neurological disorders that can benefit from DBS? DBS has been beneficial in a group of neurological diseases namely dystonia, tremors, cluster headaches and various mood disorders such as obsessive compulsive disorders, Tourette syndrome, depression and bipolar disorders. Parkinsonism and DBS: A study that was published this January in Lancet Neurology marked the technological improvement of brand new DBS devices. Dr Michael S. Okun led a group of researchers in Florida University who used constant current voltage controlled devices in DBS of the subthalamic nuclei of a group of patients with advanced Parkinson’s disease. The team used a special Neurostimulation system, called the Libra, which was created in St. Jude Medical neuromodulation Division. After implantation of the Neurostimulation system by a year, patients exhibited improvement of their motor function during periods that ranged from 4 to 12 hours per day. Apart from improvements of the motor functions, DBS aided in alleviation of the depressive symptoms of patients within 3 months following surgery. On the other hand, patients receiving DBS showed worsening of the scores of their verbal fluency. Deficits of verbal fluency represent the most common cognitive side effect of deep brain stimulation of the subthalamic nucleus. Neurologists claim that these cognitive side effects are caused by the surgery itself rather than by deep brain stimulation of the subthalamic nucleus. Fatigue, dysarthria, edema and paraesthesia are among the most common side effects following placement of the Neurostimulation device. The improvement in motor functions can be even maximized via addition of rasagiline to the treatment plan of patients following surgery. To sum up, DBS has opened new horizons for patients with Parkinson’s disease. More and more neurologists and manufacturers are getting interested in Neurostimulation which will certainly be reflected on a better quality of life for patients with Parkinsonism.

I hope no one watches Kenny Powers…the reporter Jason had a special glove mounted camera he wanted to use for the piece…obviously a baseball fan…

http://dfw.cbslocal.com/video?autoStart=true&topVideoCatNo=default&clipId=6638374

Our internal survey will likely show similar results (can’t release until we publish), but this is a much more comprehensive survey…Jennifer Born is a tireless advocate for tinnitus, her name is all over good projects…

Summary of Findings

• The size of the tinnitus population in the United States is nearly 30 million people—or about 10%.
• 13 million people report they have tinnitus but not hearing loss. However, it is widely acknowledged that people with tinnitus almost always have hearing loss. Therefore, it is likely that the hearing loss population is conceivably higher than previously reported.
• The incidence of tinnitus is as high as 26.7% for people ages 65-84 years.
• The prevalence of tinnitus is correlated with degree of hearing loss; however, it is clear that all levels of hearing loss (mild to severe) can experience tinnitus.
• Nearly 4 in 10 people experience their tinnitus >80% of the time during a typical day; slightly more than 1 in 4 people describe their tinnitus as loud; and about 1 in 5 describe their tinnitus as disabling or nearly disabling.
• Subjects with tinnitus report their tinnitus primarily impacts their ability to hear (39%), concentrate (26%), and sleep (20%).
• Of the nine tinnitus treatment methods assessed, none were tried by more than 7% of the subjects. Treatment methods rated with substantial tinnitus amelioration were hearing aids (34%) and music (30%).
• In a direct query of hearing aid efficacy, 27.8% of hearing aid users reported receiving moderate-to-substantial reduction in their tinnitus when using their hearing aids. About 2 out of 3 people experienced tinnitus relief most of the time to all of the time, while 3 out of 10 (29%) reported that the use of hearing aids alleviated their tinnitus all of the time.
• Subjects who had their hearing aids fit by professionals using comprehensive hearing aid fitting protocols are nearly twice as likely to experience tinnitus relief than respondents fit by hearing care professionals using minimalist hearing aid fitting protocols.
• Almost one-quarter of those with tinnitus describe their tinnitus as disabling or nearly disabling. There is currently no cure. This study confirms that the provision of hearing aids offers substantial benefit to a significant number of people suffering from tinnitus. This fact should be more widely acknowledged in both the audiological and medical communities.

The full article can be found here…

http://www.hearingreview.com/issues/articles/2011-11_01.asp

Impact of Tinnitus on Quality of Life

This is a fairly good treatment of the military funding issue…Col. Friedl was in charge of the program we applied to..I believe there is a better leadership now…

http://www.propublica.org/article/testing-program-fails-soldiers-leaving-brain-injuries-undetected

 

PRIMARY BLAST INJURY

An explosion generates a blast wave traveling faster than sound and creating a surge of high pressure followed by a vacuum. Studies show that the blast wave shoots through armor and soldiers’ skulls and brains, even if it doesn’t draw blood. While the exact mechanisms by which it damages the brain’s cells and circuits are still being studied, the blast wave’s pressure has been shown to compress the torso, impacting blood vessels, which send damaging energy pulses into the brain. The pressure can also be transferred partially through the skull, interacting with the brain.

SECONDARY BLAST INJURY

Shrapnel and debris propelled by the blast can strike a soldier’s head, causing either a closed-head injury through blunt force or a penetrating head injury that damages brain tissue.

TERTIARY BLAST INJURY

The kinetic energy generated and released by an explosion can accelerate a soldier’s body through the air and into the ground or nearby solid object. Once the body stops, the brain continues to move in the direction of the force, hitting the interior of the skull and then bouncing back into the opposite side, causing a coup-contrecoup injury.

With our promising results in our tinnitus clinical trial in Belgium, we have been pressing forward with our implantable device development with delivery of the Serenity System expected for the Summer of 2012.  At that point, we will be ready to begin a larger clinical trial for tinnitus using our implantable system and external controller.  This is the stage when many medical device companies are able to raise large ($20M) sums of capital to quickly expand their clinical trials to additional sites and scale up device tasks to begin biocompatibility testing and design verification and validation testing. However, we have spoken to many venture capital groups as well as current medical device companies and while they are very encouraged by the clinical trial data; they continue to doubt the tinnitus market.  We constantly have venture capitalists tell us that they do not think that tinnitus patients will accept a device that is implanted in their body because their tinnitus is not bothersome or severe enough.  We explain that the surgery for our VNS device is very routine, only takes 45 minutes, and has been practiced on 65,000 patients over the past 15 years for the treatment of epilepsy.  The venture capitalists still remain doubtful, since they don’t have tinnitus themselves.

This points to the greatest problem facing the tinnitus market – lack of awareness of the severity of the problem.  We have receive thousands of emails from tinnitus patients over the past year indicating just how desperate people are for a solution and how difficult life is for those with tinnitus.  Yet, society in general is quite unaware of the severity of the issue.  The U.S. military is spending $1.2 Billion in tinnitus disability funding EACH YEAR.  What was the total amount devoted to research on tinnitus in FY 2011?  Less than $5 Million.  Less than 1% of the annual expenditure on disability payments.  In comparison, the U.S. Military directed $150 Million for breast cancer research in FY 2011.  Tinnitus is currently the #1 disability for servicemen returning from Afghanistan.

Based on the success of our initial clinical trial in Belgium, we are pushing forward with another clinical trial in the EU in 2012; since the U.S. FDA clinical trial requirements cannot be fulfilled by us until 2013 – due to the extensive amount of device material testing required prior to the start of a clinical trial.

NIH grants cannot fund trials outside the U.S.  Thus, we need to raise $2 Million in funding to run the next set of trials if we want to run a trial in 2012.  Otherwise the development of therapy will be delayed by a year until 2013, when we can begin trials in the U.S. and hopefully receive a NIH grant.

The $2 Million in funding needs to come from “accredited investors” – individuals with a total net worth of over $1M.  The SEC rules are here. We are contemplating trying to reach out to some of the famous celebrities with tinnitus, but often they are hard to reach.  Interested investors can visit our website www.microtransponder.com and click on the link to the investor form or can email us directly at invest@microtransponder.com.  We are happy to present our clinical research and all of our development plans to potential qualified investors.

Raising this round of $2M will bridge the gap and allow us to actively pursue additional NIH grants while conducting our clinical trial in the EU.  Both venture capital investors and existing medical device companies have indicated that additional clinical trial results using our finished device in 15-20 patients would allow us to raise a large round of capital to begin selling the therapy system in the EU and conduct larger clinical trials in the U.S. as part of the FDA regulatory process to begin sales in the U.S.  (currently the device is not for sale in the U.S. or EU)  We need 20 people to invest $100,000 each.

To conclude, we are reaching out to the tinnitus community to let potential investors or officials in the military know that an effective treatment of tinnitus is just on the horizon. We have rigorous scientific standards and have passed serious NIH reviewer scrutiny. We now just need the funds to run the clinical trial as quickly as the regulatory bodies will allow.

A great article from ABC on tinnitus (video not directly related to article)

http://abcnews.go.com/Health/Depression/tinnitus-suicide/story?id=15003057#.TtcvI5SiG5L

A video from our lead PhD Neuroscientist describing our new Therapy for Tinnitus

We have received a demo for our next generation tinnitus product and have the skeleton requirements for what our stroke product should be accomplishing from a software perspective.  We have spent nearly 1000 man hours evaluating the stroke therapy from a clinical perspective and I believe we have a very accomplished team working on the manufacture of the product for the next clinical studies.   However, I’m struck with a gut feeling that medical device software development could be done differently.

I try to read 5 scientific journals and 3 books per month, so this month I read Do More Faster: TechStars Lessons to Accelerate Your Startup, How the Mighty Fall: And Why Some Companies Never Give In and Great by Choice: Uncertainty, Chaos, and Luck–Why Some Thrive Despite Them All.  Each of these books focused on ideas associated with preparing for contingencies and failing fast.  So, in keeping with the idea of the 20 mile March from Jim Collins books and failing fast as it relates to software code implementation, I really want to understand how to get more user input (MD, therapist, patient) into our software development.   While most internet/software companies can release versions and get immediate market feedback, medical device software takes years to get regulatory appooval on.  We might only get user data from 2-3 doctors and 50 patients before a market release.  This process is frustrating because I know that the intelligence of the mass mind of product development is critical…

Would appreciate any ideas on how to do this better…

This was some nice coverage on our tinnitus program with CW 33…our results with targeted plasticity were well received at the Society for Neuroscience meeting this week…here is a copy of the news story:  http://www.the33tv.com/videogallery/66150768/News/11/16/11-Vets-and-Tinnitus#pl-62859780

Giving a great boost to kick off our Angel round of fundraising, I was interviewed by a local Dallas TV station to discuss our tinnitus therapy alongside a Veteran Allen Vaught from Iraq who is suffering from tinnitus.  I need to give thanks to the American Tinnitus Association for assisting with this story and locating Veteran Allen Vaught to help the viewers better understand the condition of tinnitus.  I have inserted the video of the TV newscast below.  We have begun discussions with accredited investors to fund our additional clinical trials and device development.  If you have interest in investing in MicroTransponder, please email invest@microtransponder.com and we will follow up with appropriate information.

We have made an enormous amount of progress over the past 6 weeks including finalizing our first 3 center US clinical study plan, submitting a manuscript based on the survey we took here and we also got a paper accepted in a very high profile journal for some of the targeted plasticity work being done in the motor cortex.  We expect to submit this plan to the NIDCD on December 5th and would hope to get word on funding by March of next year. If we get a good score, we could begin enrolling patients as early as next year.

I also received a call from a Colonel asking for full debrief on our progress.  While I have been generally unimpressed with the military’s ability to organize and fund important research in tinnitus, I was really impressed with him and his team.  We submitted a pre-proposal to a grant that might fund a clinical study in the military population in 2012…keep your fingers crossed that the DoD funnels the money from ending overseas operations in Iraq to helping the soldiers who are coming back.

In writing the research plan and commercialization plan (and pulling an all-nighter on the DoD pre-proposal), I was struck by 2 things:

1. The number of therapies that are FDA approved for tinnitus treatment that have never been shown to work in a rigorous clinical study.

2. In finalizing our manuscript for the survey we ran here on the site, I switched from being pragmatic on the market analysis to wanting someone to find a solution.  This is to say, for the first time I truly believed that I would want to see a solution to this problem even if it didn’t come from us.    From the mind of a paranoid relief pitcher, this was quite an epiphany.

We hope to finish our study with 9 patients by the end of the year and then expect to announce the results at a conference/publication in 2012.

We posted a video on our therapy for stroke, but readers of this blog might be interested in our youtube channel with some more information about our programs.  Here is a good overview on our tinnitus therapy from Dr. Kilgard.  

In addition to Tinnitus, we are also developing our novel Paired Neurostimulation Therapy to treat victims of stroke that have lost motor control.  Due to similar mechanisms of action in the brain, delivering Vagus Nerve Stimulation while a stroke patient is undergoing rehabilitative exercise both increases the speed of recovery and the extent of recovery for the patient.

According to the American Heart Association, there are currently 7 Million stroke survivors and every 40 seconds, another person suffers a stroke.  Mortality from stroke has plummeted in the last decade, decreasing 45% from 1997-2001.  This means that of the 795,000 people each year which have a stroke, a large majority will survive and at least 30% will need rehabilitation to regain full motor control.  The key for the stroke survivor is to regain enough motor control so they can continue to live independently.  The inability to regain motor control often requires stroke survivors to require constant care, with an average lifetime cost of $140,000 per patient.

During a stroke, the brain experiences a temporary loss of oxygen.  This loss of oxygen causes various regions of the brain to cease to function.   Often, a stroke survivor will lose use of their limbs and must undergo an extensive rehabilitative exercise therapy to try to regain the use of their limbs.  During this process, the motor cortex in the brain is reforming neural networks to control the movements of the limbs.  Due to the loss of neural function during the stroke, the patient is often unable to regain full control and range of movement in the limbs.  Vagus nerve stimulation (VNS) has the ability to help in the rehabilitation process because the electrical signals it inputs into the vagus nerve prompt the nucleus basalis to output neurotransmitter chemicals, which in term spur the brain to more actively form neural networks and pay attention to stimuli.  In this case, the stimulus would be the movement of the limbs, which will prompt rapid expansion of the neural networks in the motor cortex of the patient and allow them to relearn motor movements at a rapid pace.

We have been working on the stroke recovery project with Michael Kilgard, PhD, an esteemed professor of Neuroscience at the University of Texas at Dallas.  Dr. Kilgard is one of the most publicized researchers on the topic of neuroplasticity.  In the video below, he describes how MicroTransponder’s novel therapy is able to help patients recover motor function following a stroke.