Will Rosellini

As busy as I have been, I’m glad my COO made me attend the Future of Medicine conference at the Singularity Institute…while it is good to remain very focused as a sensory and motor neurorehabilitation company, sometimes it is good to zoom outand pay attention to larger trends.   I thought I would post some notes from the conference speakers:

Ray Kurzweil gave his standard talk (beamed into a 3D hologram of himself) and then showed a set of graphs talking to the rate of change for IT related technologies.  His thesis assumes that given enough activity in a research space loosely defined as information technology, the rate of change will be exponential, as opposed to linear.  Check out his charts here:

http://www.singularity.com/charts/page82.html

He believes that biology has become an information technology…of course I share this view and built some projected neuroenhancement devices for the video game Deus Ex: Human Revolution.

We spent most of the morning on personal genomics, which remain far behind in their promise to revolutionize healthcare.  I did the MS in Computational Biology based on this hype, but agree with the sentiment that there is alot more work to be done to make personal genome sequencing actionable.  To date, the best advice we can give is exercise, don’t be fat, don’t smoke, keep stress low and don’t do drugs/drink.   Most genome maps would conclude the with the same treatment plan…I do think there will be some short term wins in this space as it relates to focused genomic mapping for drug dosing…of special note, I think the Warfarin dosing studies based on genomic analysis shows promise…not clear who will pay for the test though.

We spent the afternoon discussing aspects of EMR’s and mobile health…cardiologists are the farthest along in this space, but readily admit that more information isn’t necessarily helping them in making treatment decisions…this is also to say, we don’t know what to do with 24/7 data…since everything we do now is based on the office consult…this area will continue to develop as gamification (integrating games into a routine health check or patient lifestyles integration (EKG covers for iphones/seatbelts with defibrillators etc…)

Day 2 should be more interesting…however, after day 1 I still believe that neurostimulation will be the biggest “surprise” in the next 10 years…we will see if I change my tune after today.

An Overview of the history of Northstar Neuroscience, Inc.

 Northstar Neuroscience Inc. was an American company that was centered on the development and marketing of various neuromodulation therapies targeted to improve the quality of life of individuals suffering from a wide group of neurological disorders. The company was founded in 1999 and was initially named Vertis Neuroscience, Inc. which had been changed to Northstar Neuroscience, Inc. in 2003.

Renova – ST

Renova-ST was the company’s primary product which was a cerebral cortex neurostimulation system that was used to deliver targeted stimulatory current to the cerebral cortex. Since early 2000, the company had been conducting a group of clinical trials that examined the safety and efficacy of Renova-ST in the management of various neurological disorders such as stroke, tinnitus, stroke induced aphasia and major depression.

The Renova-ST consisted of a neurostimulator device, cortical stimulation electrodes and a special programming system.

-         Neurostimulator: which is an electrical stimulating device that is usually implanted under the skin of the upper chest area.

-         Cortical stimulation electrodes: which are leads connected to the neurostimulator device. They are placed over the cerebral cortex to deliver stimulating electric current to the target area of the cortex.

-         Programming system: which is a form of a portable computer that permits communication with the implanted neurostimulating device. It allows the physician to modify the parameters of cortical stimulation.

The Everest Trial

Northstar Neuroscience conducted a major clinical trial, which was known as the Everest trial, which examined the efficacy of the Renova neurostimulation system in association with special rehabilitation therapies in recovery of arm functions in upper limb hemiparesis caused by stroke. Unfortunately, as of January 2008, Northstar Neuroscience announced that the Everest trial had failed to meet its predefined main end point.

The trial’s end point was a form of a composite that was utilized to assess the gains in the functions of hand and arm after 4 weeks of completion of rehabilitation therapy as measured by the Upper Extremity Fugl-Meyer test (UEFM). The assessment also included the patients’ ability to perform normal daily activities via the Arm Motor Ability test (AMAT).

The winding down of Northstar Neuroscience, Inc.

In January 2008, John Bowers, the CEO of Northstar Neuroscience, Inc., announced that the Everest trial failed to support positive effects of cortical neurostimulation therapy on the recovery of motor stroke which was proven in past studies.  However, there has been much debate into the causes of the failure…subsequent analysis of the data has shown that if the surgical implant was done with imaging (business types cut this cost out of the pivotal study), then the results were extraordinary…by the time this was shown, the investors had taken nearly $90M dollars out of the company, wound it down and sold the IP to Advanced Neuromodulation–St. Jude.   St. Jude has not done anything in this space and recently reported a large layoff in their deep brain stimulation unit.

I met another soldier (a high school friend, SEAL) who experiences tinnitus.   The other guys at the table were surprised that he had never mentioned it before…I thought I might post briefly on some basics, just in case you want to send this explanation to your friends/family.

Tinnitus is a perception of feeling an annoying sound in the ears or the head. The term tinnitus is derived from tinnire, a Latin word which means to ring. Typically, a person falsely perceives a sound when there is no actual sound in the external environment i.e. the perception of sound is irrelevant to any external stimuli.

More than 10% of the entire population suffer from tinnitus at a point or another during their lives. On the other hand, approximately 85% of individuals suffering from chronic ear problems complain of tinnitus. The problem can affect children as well as adults; however, the incidence of tinnitus rises with age.

Occasionally, tinnitus is experienced after exposure to a loud noise as a gunshot or amplified sounds as in a music concert. Although this form of tinnitus is somehow annoying, it usually lasts only for a few hours.

What are the causes of tinnitus?

It is worth emphasizing that tinnitus is a mere symptom not a clinical disorder; hence, searching for an underlying cause is mandatory, especially when it has been present for a long period. This is of pivotal importance because tinnitus is sometimes accompanied by sensorineural hearing loss. Special forms of tinnitus such as fluctuating tinnitus, tinnitus with vertigo, pulsatile tinnitus or unilateral tinnitus must be thoroughly investigated.

Tinnitus is categorized into 2 groups:

-         Objective tinnitus: is audible to everyone including the complaining individual.

-         Subjective tinnitus: is only audible to the affected individual.

Objective tinnitus:

Objective tinnitus is rather uncommon. The sound originates in the ear, head or neck because of a vascular or a muscular cause. Muscular tinnitus associates multiple degenerative disorders of the head and neck such as amyotrophic lateral sclerosis which is a neuromuscular disorder that occasionally affects the muscles of the ear leading to myoclonus or a form of repetitive flutter of the tensor tympani and/or stapedius muscles. This leads to an audible and observable flutter originating from the ear.

Palatal myoclonus is another uncommon cause of muscular induced tinnitus. It is the result of rhythmic discharge originating in the inferior olivary nucleus in patients suffering from brainstem lesions. The disorder is usually secondary to trauma, stroke, multiple sclerosis or encephalitis.

Carotid artery aberrances are relatively common causes of objective tinnitus. Furthermore, senile ectatic changes of the carotid artery can lead to tortousity of the blood routes through the neck and ear yielding turbulent flow that can be auscultated.

The jugular vein and jugular bulb can yield a form of tinnitus that is associated with a venous hum. It is often described as a low pitch sound or vibration rather than a ringing sound.

Subjective tinnitus:

Clinically speaking, subjective tinnitus is sound perception which is unrelated to auditory stimuli. Subjective tinnitus is the result of the brain’s response to deprivation of sensory input from the auditory effector organs. Therefore, subjective tinnitus can be associated with any form of conductive or sensorineural hearing loss. These include chronic ottitis media, otosclerosis, congenital sensorineural hearing loss…etc.

Hello,

The University of Iowa is doing a survey on hyperacusis…always helpful to have people take the survey.  Microtransponder isn’t involved in this, but always like the work being done out of Iowa.

https://uiowa.qualtrics.com/SE/?SID=SV_22YHczpQkvXNHsE

–Will

The Role of Deep Brain Stimulation (DBS) in the Rehabilitation of Post-stroke Patients

Neurostimulation has gained lately a great deal of acceptance among neurologists as it has proven to be an ideal pain modulation strategy, especially in patients whose pain is resistant to other pain control modalities. Although neurostimulation of the spinal cord has been studied more than any other form of neurostimulation, neurostimulation of the cerebral cortex has lately been a valuable neuromodulation practice in the rehabilitation of patients with stroke.

Deep Brain Stimulation and Post-stroke Dysphagia:

Dysphagia is rather common following stroke as it may affect up to 50% of all affected patients. Occasionally, this leads to serious complications namely malnutrition and inccordination of the pharyngeal mobility which causes repeated aspiration. Nevertheless, the presently available lines of treatment for dysphagia are controversial and aren’t supported by considerable body of research evidence.

Paired associated stimulation (PAS) is a brand new neurostimulation technique that combines peripheral neurostimulation of the targeted muscle group with deep brain stimulation of the cortical area innervating this muscle group. PAS has been proven to be a valuable line of treatment in the rehabilitation of patients suffering from dysphagia following stroke.

PAS has led to short term changes in the cerebral cortex, heightened excitability of the pharyngeal cortex, reduced penetration/aspiration scores and improvements in the biomechanics of swallowing such as increased accuracy of swallowing during performance of complex tasks.

A clinical trial was conducted in the University of Manchester in the UK and was led by Dr Emilia Mischou who examined the effects of application of PAS to normal functioning pharyngeal motor cortex of normal patients after exposing them to an experimental stroke model or a virtual lesion leading to temporary central dysphagia. The investigated group of patients exhibited bilateral changes in their brain activity that lasted for a short period and included heightened excitability of the normal unaffected cortex. Furthermore, most patients showed improved pharyngeal mobility and coordination.

Despite the fact that Michou’s trial didn’t rely on controls and that investigated patients weren’t suffering from advanced dysphagia and pharyngeal incoordination, they showed immediate positive behavioral changes. The fact that via a single PAS treatment session, patients with post-stroke dysphagia exhibited immediate neuropsychological and behavioral changes, can predict even better results when different treatment protocols are investigated properly.

Neurostimulation and the Management of Post-stroke Pain:

Deep brain stimulation has been lately effectively utilized in the management of post-stroke pain syndromes. Neurostimulation of the motor cortex, or motor cortex stimulation (MCS), and neurostimulation of the nucleus ventralis caudalis of the thalamus yielded better pain control in post-stroke patients. However, pain was better controlled via MCS when compared to neurostimulation of the thalamus or spinal cord stimulation (SCS) suggesting that the nociceptive information are abnormally processed at the deafferentation level and progresses to higher centers.

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