This week is Tinnitus Awareness Week, here is a sample proclamation from the ATA.  I think the ATA does a great job raising awareness for this horrible condition.

WHEREAS, Tinnitus, often defined as “ringing in the ears,” causes a person to hear ringing, buzzing, or a variety of other sounds without an external cause, and to have a heightened sensitivity to sound; tinnitus can be a debilitating condition, reducing the quality of life for those chronically affected; and

WHEREAS, Tinnitus is most often the result of extreme noise exposure from either a single impulse noise or the accumulation of noise exposure, but may also be caused by conditions such as an ear infection, the use of certain medications, a blocked auditory tube or canal, or a head injury; and

WHEREAS, As many as 50 million Americans experience tinnitus to some degree, of those, approximately 16 million have chronic tinnitus and seek medical attention for their condition, and nearly two million are debilitated by tinnitus; and

WHEREAS, According to the National Institute for Occupational Safety and Health, the maximum allowable noise exposure is 85 dBA for eight hours and, even at that level, an individual can sustain hearing damage; even though there are recommended maximum allowable exposure times, cumulative noise exposure over several years, even at safe levels, can cause tinnitus; and

WHEREAS, Americans live in an age of amplified sound where many everyday noise sources produce decibel levels that can be hazardous to our hearing, resulting in tinnitus or other types of hearing loss; some everyday sounds that exceed the allowable noise exposure level of 85 dBA include those from a blow dryer, subway train, power lawn mower, chain saw, jackhammer, screaming child, rock concert, thunderclap, jet engine and an MP3 player; and

WHEREAS, The Army is the only branch of the military that requires earplugs as part of a recruit’s uniform, but many types of military equipment exceed the 85 dBA limit, including an Apache helicopter, a nine millimeter pistol and a grenade; as a result, in at the end of 2011, over 840,000 American veterans were service connected for tinnitus; and

WHEREAS, Tinnitus is the number one service-related disability suffered by military personnel returning from the current conflicts in Iraq and Afghanistan; by 2014, the United States Department of Veterans Affairs will be paying nearly $2.2 billion in tinnitus disability compensation annually to this country’s veterans; and

WHEREAS, Even with a combination of public and private funding, only 10 million dollars is spent on tinnitus research in the United States, far less than what is spent on research for most other medical conditions; and

WHEREAS, Current therapies used to treat tinnitus cannot permanently rid a patient of the condition, and not all tinnitus patients benefit from the different treatments currently available, but new, sophisticated brain-imaging technologies have allowed researchers to identify the areas of the brain that involve tinnitus and have led scientists to study tinnitus on several new fronts; and

WHEREAS, Tinnitus is a condition that can affect anyone, young or old, and increased public awareness of the condition’s debilitating effects should be promoted to encourage both public and private health care organizations to provide funding for continuing  research on ways to alleviate the symptoms of tinnitus, and to find a cure for this incapacitating condition; now, therefore,

BE IT RESOLVED by the (House or Senate or other government agency/body) of the State of:_______________

1.    This (House/Assembly/Legislative body) hereby declares the week of May 13 through May 19, 2012 as “Tinnitus Awareness Week” in the (State/town/city/county) of XXX to promote public awareness about the debilitating effects of tinnitus in order to encourage both public and private health care organizations to provide funding for continuing research on ways to alleviate the symptoms of tinnitus, and to find a cure for this incapacitating condition.

2.    The (Governor/Commissioner/other elected or appointed representative) is requested to issue a proclamation calling upon public officials and the citizens of this State/County to observe “Tinnitus Awareness Week” with appropriate activities and programs.

3.    A duly authenticated copy of this resolution, signed by the President of the (Senate or House or other legislative body) and attested by the Secretary of the Senate, shall be transmitted to the American Tinnitus Association.

Serenity System for Tinnitus – 10-Patient Clinical Trial Successfully Completed

Spring is an exciting time for MicroTransponder.  The 10-patient tinnitus clinical trial demonstrated that our Serenity System* therapy is able to clinically reduce tinnitus in the patients.  Using the Tinnitus Handicap Questionnaire, 70% of the patients experienced a significant reduction in their tinnitus.  This is just one of the positive outcomes of the trial.  We will be presenting our entire set of clinical data Tinnitus Research Initiative Conference in Belgium this June.

Angel Round to Fund EU Clinical Trials Nearing Completion

Building upon the success of our tinnitus clinical trial, MicroTransponder has been raising an extension of our B round of funding.  We would be happy to discuss an investment opportunity with any additional investors as we expect to close this Spring.

Post Stroke Motor Therapy Being Prepared for Clinic

In November of 2011, the MicroTransponder research team published a paper in Cerebral Cortex which described how our unique paired vagus nerve stimulation therapy is able to generate significant changes in the motor cortex in animals following a simulated stroke.  This indicates that our therapy might be able to assist in treating a number of neurological indications related to movement deficit.  Further clinical testing is needed, but we are hopeful that we can help the nearly 800,000 patients who have strokes each year.  Many stroke survivors are not able to regain command of their upper limbs.  We are preparing our paired vagus nerve stimulation therapy for a clinical trial that will attempt to reproduce the rapid motor recovery we witnessed in the animal studies.  This stroke clinical trial could begin as early as Fall 2012.

Scientific Publications

In Q1, we submitted 5 papers to academic journals for publication.   One of them has been accepted for publication.  This paper covers the work in Phase I of our active U44 NINDS cooperative development program.  Here is a summary of the submissions:

1) “In vivo tests of switched-capacitor neural stimulation for use in minimally-invasive wireless implants”.  This manuscript discusses the MTI exponential waveform and demonstrates sciatic nerve activation in rats by measuring cortical responses.

2)  “A novel waveform to generate paresthesia with selective nerve fiber activation”.  Compares the exponential pulse to a conventional rectangular pulse in a clinical setting.

3)  “Effects of electrode spacing on nerve excitation with voltage controlled capacitive discharge”. Describes our four electrode configurations to demonstrate which electrode size/spacing activates the nerve better.

4)  “SAINT: A wireless peripheral nerve stimulator”. Details the SAINT wireless neurostimulator design and performance.

5)  “Wireless Peripheral Nerve Stimulation Increases Pain Threshold in Two Neuropathic Rat Models”.  Describes the preclinical studies conducted with the SAINT wireless neurostimulator and demonstrates that the MTI exponential pulse can improve pain symptoms.

Closing

We are seeing the clear signal that our therapy is working.  After decades of tinnitus research, we now have a trial showing positive short-term outcomes for tinnitus patients who have previously failed other treatments.  We are very excited to be very close to finishing our current round of funding and focusing back on clinical trials using a fully implantable device that is ready for clinical trials and commercialization.  We hope to bring this therapy to the patients as soon as possible.  We see the exciting promise of our therapy in other areas of neurological disease as well.  Please reach out if you would like to help us reach this goal.

– Will Rosellini, CEO

* CAUTION–Investigational device. Limited by Federal law to investigational use.

I’ve reached nearly 30,000 views on this little blog and received 100s of emails.  I am sorry to each and every one of you suffering from tinnitus, but I must be very careful in my responses.   We have our current clinical results in hand and I believe we will have good news to share on our fundraising efforts soon.  Our clinical results will be presented at the TRI conference in Belgium in June.

The FDA has provided a set of guidelines that dictate how I am allowed to discuss our results/information publicly.  I hope this makes it clear that we take our responsibility to not make unsupported off-label claims (everything is off-label since we don’t have an approved product).   I post some of the language below:

The draft guidance has a lengthy section dealing specifically with requests for off-label information encountered through what the FDA characterizes as “emerging electronic media,” such as product websites, discussion boards, chat rooms, company-controlled electronic forums, and third-party sites over which companies do not maintain control.

In these situations, the FDA apparently is concerned that companies might post detailed public online responses to questions about off-label uses of their products in such a way that they are communicating off-label use information to individuals who have not requested that information. The FDA also is concerned about the “enduring nature” of detailed public online responses to off-label questions because specific information may become outdated. Accordingly, the draft guidance contains a number of recommendations that essentially enables a company to respond to a public request privately.

First, the FDA recommends that a company respond only when the request pertains specifically to its own named product (and is not either generic or solely about a competitor’s product). Thus, for example, if an individual poses a non-specific question such as “What drug can be used for Condition Y” in a public communication thread and a pharmaceutical company manufactures or distributes a drug that is not FDA-approved or cleared for that condition, the company should not respond to the request because the question is not specific to its drug.

Even when an unsolicited request for off-label information is posed as to a specific drug or device, the FDA also recommends that a company’s public response be limited and should not include any off-label information.

The response should convey that the question pertains to an off-label use and state that individuals can contact specifically identified medical/scientific representatives of the company or its medical affairs department for more information. Contact information for the specific individuals should be provided so that individuals can follow up independently with the company to obtain specific information about the off-label use of the product through a non-public, one-on-one communication. The company representatives who provide public responses should clearly disclose their involvement with their company. In addition, a public response should include a mechanism for providing readily accessible current FDA-required labeling, if any, for the product (such as an FDA-approved package insert, an FDA-approved patient labeling or, for new animal drugs, an FDA-approved client information sheet).

The first task was to come up with a name for our new system to treat tinnitus.  We had discussions with many patients and asked them to describe the emotional impact of tinnitus on their life.  Many tinnitus sufferers described the extreme annoyance, persistence, and agony of their tinnitus.  Many described a strong yearning to again be able to experience “peace and quiet”.  With this in mind, the name “Serenity” was chosen.  Serenity means calm, peaceful, and tranquil.  It has a latin root and has a strong emotional component.  We believe that our tinnitus therapy will help provide our patients with serenity once again in their lives.

The next stage was to make sure that the word “Serenity” did not mean anything offensive in other languages of the countries that we may one day sell our product.  We did a check with all the major European languages and also made sure that there was no prominent product that already was known as “serenity”.  (A classic example is the Chevy Nova – which in Spanish means “Does not go.”)  A more recent example in the pharmaceutical space was the launch of the drug Tergretol Retard.  It was launched by a French company, who did not check to see what their name might mean in other languages.  It was especially awkward because some of the patients using the drug had mental health issues.

Once we chose the name “Serenity System” as the name for our therapy and device, we needed to do a trademark word search in the U.S., Australia, and Europe.  This was to make sure that there were no other medical devices related to tinnitus or neurostimulation with the exact same name or something very close.  In order to prevent several companies from all having products with the exact same name and generating consumer confusion, the U.S. Patent and Trademark Office encourages companies to register their product name trademarks and only allows 1 name for a given type of product.  There appears to be a Pharmaceutical company with the name of Serenity, but they are developing a drug for nocturia, so there is not likely to be any confusion with tinnitus.  So we are good on that front.

The next step was to get a design created for the Serenity logo.  There are several websites that have a competition model for this purpose, where the client writes a creative brief, sets a prize amount, and then the competition begins.  We chose to use www.logotournament.com The brief we wrote included a description of tinnitus as well as a description of our therapy.  Some designers submitted logos that included sound waves, ears, seashells, swirls, water images, and other serene designs.  A very creative group and over 200 designs were submitted over a 8 day period.  It was a tough choice, but given the emotional power of the word, we needed an image that conveyed a true sense of serenity.

Here is the winning logo:

We need to choose a Serenity logo and would like to invite the tinnitus patient community to provide input.  We are using this logo for both our website as well as on the device itself, so the color is not as important as the actual text and graphics.  Once we settle on a logo we like, we can have it rendered in whatever color we need.

The contest runs until Monday March 5, so feel free to visit the contest and give feedback on which design you like the best.  Be sure to reference the number at the bottom of the logo design.

We appreciate all of your help!

visit

http://logotournament.com/contests/microtransponder/

and post your preferences in the comment section below.

Or you can rank the logos in the tournament by clicking on this link – may only work for a limited time.

http://logotournament.com/contests/microtransponder/friendfeedback/W935970V56

thanks,

Will

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.

 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.

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.

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

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.