In 2012, researchers from Emory University published a paper on their finding of a substance that increases the effectiveness of GABA in people with central disorders of hypersomnolence, particularly idiopathic hypersomnia. In that paper, they discussed their findings in seven patients who were treated with flumazenil. In 2014, Kelty et al published a case report on the use of flumazenil given intravenously to a single patient for 96 hours and then implanted under the skin. The current paper from the group of Emory researchers includes information from additional patients who were treated with a compounded version of flumazenil.
What kind of a study was this?
This was a retrospective study, meaning that the researchers did not set out ahead of time to perform a research study with predetermined goals and questions. Instead, two neurologists prescribed the medication, flumazenil, as part of their routine practice to all appropriate patients who came to their clinic. Then, at a later date, they formulated their questions.
Who were the patients and what did they do?
One hundred fifty-three patients (92 women) were prescribed flumazenil by the physicians at Emory.
Who were the researchers and what did they do?
Dr. Trotti and her colleagues at Emory University reviewed the charts of their patients with hypersomnolence for whom they had prescribed flumazenil. They also reviewed the patients’ electronic correspondence and pharmacy records.
What were the results of the study?
Ninety-six of the 153 (63%) patients reported that they were less sleepy after taking flumazenil. On the other hand, 19 people reported that they were more sleepy after taking flumazenil. Among these 19 patients, nine continued taking flumazenil because the increased sleepiness was only temporarily worse right away after taking the medication or the sleepiness improved after the flumazenil dose was changed.
Before starting treatment, the average ESS score was 15.1, even among those who were taking wake-promoting agents. After starting treatment with flumazenil, the average ESS score dropped to 10.3 among the 40 people who reported improved sleepiness and who completed a second ESS.
Of the 96 patients who reported that their sleepiness improved in response to treatment with flumazenil, 59 continued to take the drug long term (average, 7.8 months at follow-up). Interestingly, 72% of women reported a positive response to the drug, whereas only 48% of men had a positive response. Similarly, people who reported having sleep inertia (difficulty waking up, including grogginess or disorientation immediately upon awakening) were more likely to respond to flumazenil, as compared with those without sleep inertia (72% vs 42%).
Seventy-nine participants (52%) reported experiencing an adverse event (the most common being dizziness, anxiety, and headache), with 17 people stopping the medicine because of adverse events. Two patients had serious adverse events, and another had changes in liver function tests that resolved after stopping the drug.
What were the researchers’ conclusions?
According to the authors of this study, “In summary, our clinical experience in a large group of patients with treatment-refractory hypersomnolence demonstrates meaningful and sustained clinical response in a substantial fraction of patients. Important questions remain about optimal formulation, dosing, long-term safety, and effectiveness. Prospective, controlled studies, ideally with measurement of plasma or cerebrospinal fluid flumazenil levels, are clearly needed. However, our experience suggests the possibility of clinical use of flumazenil in carefully selected, severely affected patients lacking other treatment options.”
Trotti LM, Saini P, Koola C, LaBarbera V, Bliwise DL, Rye DB. Flumazenil for the treatment of refractory hypersomnolence. J Clin Sleep Med 2016;ePub ahead of print.
During the presentation by David Rye, MD, PhD titled “What are the latest developments in research on idiopathic hypersomnia?” at the Beyond Sleepy in the Mile-High City Hypersomnia Conference, he pointed out that, while on the one hand without a known biological biomarker there is a large unmet clinical need for people with idiopathic hypersomnia, on the other hand a growing awareness garnering increasing interest and recognition within the medical community is gaining momentum.
Following is an abbreviated summary of his talk prepared by Dr. Michelle Emrich. As Dr. Rye had mentioned this is not an all-inclusive list but specific highlights of recent development in research, collaboration, and treatments of idiopathic hypersomnia:
- In the fall of 2016 The Emory University sleep research team and collaborators anticipate applying for a newly announced FDA orphan products natural history grant that has the possibility to yield $400,000/yr of additional financial support for up to 5 years.
- Nearly half of chronic fatigue syndrome patients meet MSLT criteria for IH. Data not yet published. Population based control MSLTs (n=1019) summarized courtesy of E. Mignot vs. CFS (n=46) from Wichita, KS (Reeves WC, et al BMC Neurol (2006); 6:41).
- Studies of non-sleepy controls indicate that nearly ¼ (22%) are asleep by 8 minutes, which demonstrates that MSLT based criteria of ≤ 8 minutes put forward by the International Classification of Sleep Disorders (ICSD) is poor at discriminating IH from controls (i.e., it is a “poor” test in lacking specificity).
- 71% of IH with long sleep have MSLT > 8 min (i.e. considered to be normal), showing that MSLT based criteria also have poor sensitivity for rendering a diagnosis of IH (C Vernet and I Arnulf, Sleep (2009)).
- A “cluster analysis” (i.e., unbiased probing for the degree of commonality ofsymptoms) by Sonka, Susta and Billiard suggests that IH and Narcolepsy Type 2 (NT-2) share more similarities than differences. (Narcolepsy with and without cataplexy, idiopathic Hypersomnia with and without long sleep time: a cluster analysis. Sleep Medicine 16(2):225-31).
- Dr. David Plante (U. Wisconsin) is continuing his work looking at hypersomnia in affective disorders (e.g., depression and bipolar disease). Sleep propensity in psychiatric hypersomnolence: a systematic review and meta-analysis of MSLT findings. Sleep Medicine Reviews – in press (2016).
- Dr. Plante has a five-year K23 training grant from the National Institutes of Health (NIH). Research
- Aim #1: to probe for deficits in slow wave electroencephalogram (EEG) activity in depression with hypersomnolence as standard sleep variables demonstrate increased sleep duration with normal efficiency in major depressive disorder (MDD) with comorbid hypersomnolence.
- Aim #2: increased EEG slowing during wakefulness. Global reductions in pre/post sleep waking theta frequency band in MDD without hypersomnolence (relative to controls and hypersomnolent group).
- Aim #3: Investigate slow wave induction as a treatment strategy. Subject recruitment is planned for Fall 2016.
- Dr. Plante has also been successful in getting a strategic research award from the American Sleep Medicine Foundation (ASMF) to test the usefulness of a multidimensional assessment in improving the evaluation and treatment of hypersomnolence. Questions he’ll be looking at with this research award:
- Do novel objective hypersomnolence measures incorporated into routine MSLT workflows capture aspects of hypersomnolence not quantified by current standards?
- Is the Hypersomnia Severity Index a valid subjective measure in patients referred for evaluation of suspected CNS disorders of hypersomnolence? This is a new index he’s developed.
- Do novel objective measures of sleepiness and the Hypersomnia Severity Index faithfully capture improvement with treatment?
- Dr. Lynn Marie Trotti (Emory University) also has been awarded a K23 training grant from the NIH relevant to IH and hypersomnia.
- Aim 1: Define functional neuroimaging signatures of pathological sleepiness of different etiologies (IH vs. Narcolepsy Type 1 during WAKE). She anticipates unique signatures by disease state diagnosis in FDG-PET regional hypo- metabolism. She hypothesizes that in the resting state functional magnetic resonance imaging (fMRI) will reveal increased connectivity within what has been termed the brain’s “default mode network” (DMN) whereas portions of this brain circuit will deactivate when subjects perform a simple cognitive task (N-back). Diffusion Tensor Imaging (DTI) – decreased fractional anisotropy will also be explored. Aim 2: Brain circuits underlying the symptoms of sleep drunkenness in IH will be explored with similar imaging modalities.
- Dr. Andy Jenkins’ (Emory University Depts. of Anesthesia and Pharmacology) research continues to move forward. Midazolam and other drugs in the benzodiazepine class exert their sedative actions via gamma-amino-butyric acid (GABA) by binding between the alpha and gamma subunits of the GABA-A receptor. Dr Jenkins and his team are attempting to decipher precisely the presumptive somnogen that contributes to hypersomnia in many IH and NT2 patients that is acting on the GABA-A receptor. They are methodically exploring the % change in small, GABA-mediated current results after making single amino acid substitutions on the alpha2 subunit of the GABA-A receptor. So far they have successfully identified how small changes dramatically influence how well GABA does its job.
- Is somnogen bioactivity specific to IH or might it be a biomarker for other origins of hypersomnia/hypersomnolence? The large NIH R01 grant awarded to Emory University and Dr. Rye supports studying this by comparing IH & NT2 and their spinal fluids with clinical features and spinal fluids collected from sleepy and non-sleepy sleep apnea patients, and non-sleepy controls. They are also anticipating assessing Kleine-Levin-Syndrome (KLS) patients both when in and out of their episodes of hypersomnia.
In order to help discover/define the biological pathways in which the somnogen calls “home” as well as, ultimately, the very nature/structure/chemical identity of the somnogen itself, the Emory University sleep research team is collaborating with:
- Dr. Nicholas Seyfried – Assistant Professor in the Emory Dept. of Biochemistry is the lead investigator applying proteomic methods to spinal fluid samples.
- Dr. Art Edison – A University of Georgia (U) Georgia Research Alliance scholar is the lead investigator applying metabolomics methods to spinal fluid samples.
- Dr. Mark Bouzyk – Founder and Chief Scientific Officer of AKESOgen – is studying genetics
- Dr. Gary Bassell – Chairman of Emory’s Dept. of Cell Biology – is especially interested in studying myotonic dystrophy patients (in whom hypersomnia is a prominent symptom). RNA splicing abnormalities in myotonic dystrophy cause problems with proteins derived from RNA. The GABA 2γ receptor subunit in myotonic dystrophy because of this altered splicing yields a receptor more sensitive to the effects of the sedating benzodiazepine midazolam (see above).
Genetics/Molecular Biology– Daly DD and Yoss RE A family with narcolepsy (Mayo Clinic Proceedings (1959) 34:313-319). Dr Rye spoke about this during this conference as well as at the 2015 Hypersomnia Foundation Conference. Four generations of this family were identified. Narcolepsy Type 1 is now known not to be as heritable as the sleepiness described in this family. Only 3 of 13 (16) of these family members exhibited cataplexy. So hypersomnia/hypersomnolence, not Narcolepsy Type 1, appears to be what’s being inherited in this family. Dr Rye also showed several smaller family trees collected at Emory, in which IH, Narcolepsy Type 2, and long sleepers cluster together in families.
Toward genetic research Dr. Rye/Emory has collected $187,500 in donation commitments to begin studies of the genetic components underlying IH and related disorders. The overall goal is to raise $250,000 to fund these preliminary studies, and using this data to position themselves to apply for larger streams of NIH or foundation funding. They are in the process of collating samples and deciding how to best assign diagnoses given the diagnostic challenges alluded to above (e.g, IH vs. Narcolepsy Type 2 vs. long sleepers). The team is also discussing internally and with external collaborators what best first strategies to employ (Genome Wide Association Studies (GWAS) vs. whole exome sequencing [which would be feasible and possibly more fruitful with larger families inclusive of affected and unaffected individuals]).
Most comparable GWAS studies require ~ 1000 samples. The Emory sleep program has 825 plasma samples, 783+ DNA samples, 473 CSF samples. Including DNA samples collected since November 2015 waiting cataloging into their larger biorepository.
Also, 11 patients with repeat CSF samples have been collected under different clinical conditions, which should be very useful for determining what features are unique to wellness vs. hypersomnia by way of proteomic and metabolomics comparisons.
Very recently skin biopsies h=are being collected to derive fibroblasts from which they are then able to morph into immature brain cells to study more intensively, and in a repeated manner.
Clinical Trials & Treatments: Pentylenetetrazol (PTZ; aka BTD-001). This is an anti-GABA-A receptor study drug with mechanism action similar to that of clarithromycin. It is being further developed/studied by Balance Therapeutics for the treatment of cognition and memory deficits in Down’s Syndrome as well as hypersomnia/hypersomnolence in IH and Narcolepsy Type 2. Interestingly, PTZ is still available as one ingredient (viz., cardiazol) of a cough syrup available in Italy. This is the ongoing clinical trial with the acronym of ARISE. Www.arisestudies.com is the first industry sponsored clinical trial of any treatment seeking FDA approval for treatment of IH. This trial is testing the efficacy of Pentylenetetrazol (PTZ) in a rigorous, controlled, crossover, and blinded design. ARISE is actively enrolling patients at > 20 centers including Emory University (see the website for participating centers). This drug has a long and substantial safety record (i.e,. Phase 1 requirement of safety in humans has already been established). A small, unblinded Phase IIa study – 5 subjects (3 IH and 2 Narcolepsy Type 2) each with hypersomnia responsive to clarithromycin and/or flumazenil demonstrated very promising results. So much so that the much larger Phase IIb study is moving forward necessitating recruitment of 120 subjects (60 each with IH and Narcolepsy Type 2).
Emory’s open label experience with flumazenil continues to be promising and publication of their “open-label” experience in an initial 153 treated patients is forthcoming. The paper was accepted June 27, 2016 publication in the Journal of Clinical Sleep Medicine. Beyond this experience which is limited to those patients seen and treated by Drs. Rye or Trotti prior to January 1, 2015, it is estimated that nearly 300 patients with hypersomnia resistant to traditional treatments with wake promoting drugs have been empirically treated with flumazenil through Emory’s outpatient sleep clinic alone. Many additional physicians outside of Emory are increasingly prescribing flumazenil to their patients.
Much has transpired since the 1950’s when Dr. Bedrich Roth coined the term “idiopathic hypersomnia” and progress will continue as we work together and tease out understanding of the causes of idiopathic hypersomnia.
Can you believe that 2016 is almost half over? It’s been a very busy year at the Hypersomnia Foundation, where volunteers have been hard at work establishing new programs and bringing you the latest information on the central disorders of
Not only do the members of the Board of Directors work tirelessly on your behalf, but they also all make the Hypersomnia Foundation a priority in their charitable giving. However, we can’t do it alone. Although we understand that not everyone has the means to simply write a check or transfer an appreciated stock, the continued success of the Hypersomnia Foundation is dependent upon your financial support. We offer you here several additional creative ways to support our continued efforts to meet these challenges you have set ourt for us.
Company Matching Gifts – Several donors have employers who match their gifts to the Hypersomnia Foundation – even a small donation makes a big difference when you double the opportunity to support people with hypersomnia!
Recurring donations through credit card or PayPal – A small monthly gift certainly adds up over time and is easy when you set it up to occur automatically. You don’t have to remember to make that payment, but what you can remember is the impact you will have on the hypersomnia community through your support.
Employee-Advised Grants – We received the grant from the Trip Advisor Charitable Foundation when a dedicated Hypersomnia Foundation volunteer nominated us late last year for her company’s giving program. We were invited to submit a proposal and make a presentation, which resulted in the aforementioned funds to increase awareness of hypersomnia among the general public and physicians. Perhaps your company has a similar program and a simple inquiry can make a world of difference
Friends and family helping friends and family – Many of the donations that we receive are in honor of someone who has hypersomnia. Talk about spreading the love!
AmazonSmile – Do you shop ANYTHING Amazon? If you designate the Hypersomnia Foundation as your charity of choice at amazon.smile.com, Amazon will donate a percentage of your eligible purchases to the Hypersomnia Foundation at absolutely no cost to you. Last year we were received several hundred dollars from AmazonSmile. Every bit counts!
Bravelets – A supporter set up a shop through Bravelets, where $10 from each item purchased is being donated to the Hypersomnia Foundation. When she set up the campaign, the supporter sent us this note, “Welcome! I came across this wonderful website a couple weeks ago. There are so many great fundraisers already started, but I noticed there was not one for hypersomnia yet! As someone who was diagnosed with hypersomnia, I know how hard it can be to be brave in the face of this frustrating and sometimes confusing illness. Please join me in spreading the word and helping the Hypersomnia Foundation.” https://www.bravelets.com/bravepage/hypersomnia-awareness-bravelets
Do you have a creative way of giving to the Hypersomnia Foundation? Please let us know, and we will gladly share it with others in an upcoming edition of SomnusNooze.
The Hypersomnia Foundation Board of Directors is thrilled to announce the launch of the Hypersomnia Foundation’s Registry at CoRDS (Coordination of Rare Diseases at Sanford). Whether you have idiopathic hypersomnia, Kleine-Levin syndrome or narcolepsy type 1 or 2, please enroll in the Registry today to help solve the puzzle of hypersomnia. Your information will help researchers comprehend the journey that people with hypersomnia travel in their search for a diagnosis and will answer many other questions, including the symptoms that you experience, which may help to distinguish among these disorders, and the treatments that have and have not worked for your symptoms. Registration is simple (the second figure below describes the process). Simply go to http://www.sanfordresearch.org/cords/ and click on the ENROLL NOW button. Your answers to the Registry questions will help researchers design better diagnostic tools and more effective treatments and, eventually, find a cure. CoRDS personnel are available to help you, if needed, during the registration process. They can be reached at firstname.lastname@example.org or 1 (877) 658-9192.
June 12, 2016, is the date. Noon Mountain Daylight Time (MDT) is the time. And, as promised, registration for the Livestream feed of Beyond Sleepy in the Mile High City: a Hypersomnia Foundation Regional Conference is now open. Thanks to the generous support of our sponsors—Balance Therapeutics, Inc., and Flamel Technologies, SA—you, your family, friends, classmates, teachers, coworkers, and anyone else you would like to invite can attend this broadcast of the event free of charge. However, you will have to provide your own refreshments during the 2:00 break.
This unique program is an opportunity for you to hear the latest research about idiopathic hypersomnia (IH), learn behavioral techniques to live better with IH, and find out how you can help to advance the science and treatment of IH by participating in research studies and the Hypersomnia Foundation registry. Have you ever had difficulty explaining IH to your friends or family members? Do your coworkers and the HR department struggle with understanding why you might need an accommodation to come in a little later or to work a flexible schedule? If so, we encourage all of the important people in your life to join you in watching, or invite them to tune in from wherever they might be to, Beyond Sleepy in the Mile High City: a Hypersomnia Foundation Regional Conference.
Registration is simple.
Anytime before noon MDT on June 12, 2016, you can register for the Livestream feed. It is recommended that you complete registration using the device that you will be using to watch Beyond Sleepy on the 12th.
Please follow these steps to register:
On June 12th, simply go to http://www.hypersomniafoundation.org/login. If you are using the same device with which you completed the registration process, you should be automatically logged in and redirected to the Beyond Sleepy in the Mile High City Livestream feed. However, depending on your computer settings, you may be required to log into the system manually. To do so, enter the username and password you provided during registration if prompted to do so on this login page.
A very few tickets are available for the in-person Beyond Sleepy in the Mile High City: a Hypersomnia Foundation Regional Conference on June 12, 2016, in Denver, CO. For more information and to register, please visit http://www.hypersomniafoundation.org/2016-hypersomnia-regional-conference.
Social Security Disability Series: Part 1
Sleep Disorders and Your Job – What To Do When The Writing’s On The Wall
By Anjel Burgess, JD
Jennie is a 40-year-old single mother of two children who has been working for 10 years as a data entry clerk. Jennie was diagnosed with idiopathic hypersomnia one year ago and has been working with her doctor to try and manage her progressively worsening symptoms. Over the last year, they have tried every medication conceivable, and her current medications have her optimal productivity time at about 3 hours. Jennie has been arriving to work late, struggling to stay awake at work, and sneaking breaks throughout the day to rest and is only able to be productive for about 3 hours throughout the day. Her supervisor has found her asleep at her desk on multiple occasions, and Jennie finds that her once impeccable work product is now riddled with errors. She was recently written up for performance-related concerns, which means that, at this point, the writing is on the wall. With a family to provide for and medical treatment that is vital to receive, Jennie is concerned that she will be fired. She has consulted with her employer, and has been told that she has the following options available to her:
In Jennie’s case, her best option is to apply for short-term disability, with a plan to apply for long-term disability benefits once her short-term disability benefits are exhausted. Once she leaves work to begin her short-term disability benefits, Jennie should also apply for Social Security disability benefits.
Social Security disability – Jennie is eligible for Social Security disability benefits based on her work history. Through her employer, Jennie has been paying FICA taxes, which makes her eligible for financial assistance and health insurance through Social Security disability in the event that she becomes disabled and is unable to work for a year or more. Since the process for Social Security benefits typically takes two years to complete, it is in Jennie’s best interest to apply as soon as she stops working so that she can ensure that her financial support from short-term and long-term disability will carry her through while she waits for the process to be completed.
If you, too, are struggling to maintain your employment due to the symptoms flowing from idiopathic hypersomnia or any sleep disorder, don’t wait until the writing is on the wall for your termination. Secure your eligibility for short-term disability and long-term disability benefits today through your employer. Contact a qualified Social Security Disability Attorney to assist you with an application for benefits.
Anjel Burgess is a partner/attorney at the Law Firm of Burgess and Christensen located in Marietta, GA. She exclusively practices Social Security Disability Law for adults and children, as well as the ancillary areas of Guardianships and Special Needs Trusts. By doing so, she has been able to make a positive difference in the daily lives of people who need help the most. You may reach her at Anjel@DisabilityHelpLine.com or 770-422-8111. You can learn more about her services at www.DisabilityHelpLine.com.
Very recently, the Hypersomnia Foundation became aware of an opportunity to help shape the future of sleep research. The National Institutes of Health, the primary source of funding for medical research in the United States, has issued a Request for Information, which you can view at: https://grants.nih.gov/grants/guide/notice-files/NOT-HL-16-312.html.
The final date to submit your comments has been extended to today, May 16, 2016.
Last week, we sent an email to everyone in our database to encourage you to make your voices heard. We are urging you again to act today. Please share your hypersomnia story with the people who determine medical research priorities and allocate funds.
- Tell them why the currently available diagnostic tools and lack of awareness about hypersomnia led to a lengthy delay in your diagnosis.
- Tell them why research into the cause of and effective treatments for hypersomnia are so desperately needed.
- Tell them why we need a cure as soon as possible because hypersomnia is limiting your ability to achieve your dreams, complete your education, or even provide financially for your family.
Please join your voice with ours as we fight to secure the place of hypersomnia at the top of the nation’s sleep research agenda. The Hypersomnia Foundation Board of Directors has submitted the following response, and we encourage you to send your comments and suggestions to the NIH, as you deem appropriate, at email@example.com.
to the National Institutes of Health’s Request for Information:
For nearly a century, the study of sleep and its function(s) in health and disease has been principally focused within approaches that center on not enough sleep. Although excessive daytime sleepiness (EDS), cognitive dissonance, and other symptoms not surprisingly result from sleep deprivation, central disorders of hypersomnolence (CDH; e.g., idiopathic hypersomnia, Kleine-Levin syndrome,
narcolepsy type 1 [NT1], and narcolepsy type 2 [NT2]) in humans (in which EDS is often accompanied by extremes of sleep length) emerge spontaneously. Studying patients with CDH has already proven to be fertile ground for investigation, as evidenced by the discovery that loss of brain hypocretin causes narcolepsy with
cataplexy (i.e., NT1). Yet, for the other CDH, there remains a large unmet clinical need, with further research and development prime for discovery and the potential for extraordinary translational opportunities.
Symptoms of CDH can be disabling, and because, for example in NT1, they also begin in adolescence or young adulthood, are chronic, sometimes progressive, go undiagnosed or misdiagnosed for decades, and respond variably to medications.
Despite advances around NT1, the knowledge gained has not translated smoothly to
the clinical realm. Diagnoses of CDH inclusive of NT1 since 1975 have relied upon a
forty-year-old test (viz., the Multiple Sleep Latency Test [MSLT]) that is cost, time,
and labor intensive and that was born of practical necessity and subsequently
tweaked to specifically identify NT1. In 2006, two preeminent sleep researchers concluded that the MSLT yields “a large number of false-positives” and that an increased daytime propensity to REM-sleep—traditionally accepted to be the sole domain of NT1—does “not appear to have any specific pathognomonic significance.” Yet, in 2016, the MSLT remains the gold standard that drives diagnoses and all that it implies. For clinician scientists, this means, for example, how clinical trials are designed and studies of heritability are conducted. Even more so, for patients, this has enormous implications for prognosis, treatment choice, access to medication(s), and accommodations/disability status.
There are currently no FDA-approved treatments for the CDH—medication choice being limited to those for narcolepsy. Since the 1930s, conventional
psychostimulants such as ephedrine have been used to treat NT1. The majority of the current pharmacological armamentarium and drug development are similarly designed and focused upon promoting wakefulness by enhancing brain monoamines. Drugs more directly designed to replace hypocretin continue in development 16 years after the discovery of hypocretin. An alternative construct in approaching the biology and treatment of CDH has recently been proposed that appears to hold great promise for many patients. People with CDH without NT1 (i.e., hypocretin being intact) do not appear to suffer from any “loss of function” per se but, rather, a gain of function in sleep-promoting brain circuits. Thus, pharmacologic agents that antagonize the sleep-promoting and consciousness-dampening neurotransmitter gamma–aminobutyric acid (GABA), such as flumazenil, clarithromycin, and pentylenetetrazol, have either been demonstrated to be effective or are in clinical trials for CDH patients in whom traditional wake-promoting agents have not been helpful.
We advocate for initiatives to fund discovery research that translates to improve the human condition of people with CDH in whom sleep is prolonged and ostensibly persists into “wake.” Enhanced recognition and improved treatments call for greater understanding of not only the clinical spectrum of CDH and the natural history of these disorders, but also mechanistic understanding of their biological underpinnings. Diagnostic tools that are highly discriminative and designed to capture more than just EDS and an increased daytime propensity to REM sleep are an absolute necessity. CDH remain diagnoses of exclusion such that greater understanding of potential mimics—which themselves would enhance mechanistic understanding of sleep—and biomarker discovery are also high priorities. As there are numerous stakeholders in such endeavors, as evidenced in the summary provided above, the absolute need to encourage greater dialogue and collaboration among patients, patient advocacy groups, professional organizations representing sleep physicians, funding agencies, and industry cannot be understated. With increasing dissemination of knowledge through many means, not the least of which includes social media, patient consumers with CDH-like symptoms have become increasingly knowledgeable. They are acutely aware that CDH outside the realm of NT1 is not well served by current medical knowledge or practice in this realm. Accepting the status quo risks alienating the public and medical consumer.
We would, therefore, propose including a sleep neurobiologist on the NHLBI Sleep
Disorders Research Advisory Board and developing mechanisms for solicitation of
program projects and set-aside funds specifically to research hypersomnia, with requests for proposals to prioritize filling unmet clinical needs in the following areas:
R37 Javits Neuroscience Investigator Award
NIH EUREKA grants
R13 funding to support conferences
T32 grants for postdoctoral study
RFAs and more specifically RFPs
SBRI funding for better diagnostic tools
Because the breadth of scientific inquiry or line of investigation needs incredible resources and sustainability, we would advocate for funding initiatives with set-aside monies at all levels of training, including predoctoral, doctoral, postdoctoral, junior investigator, and senior investigators, and we envision promoting set-aside monies for all the Career Development K Awards for investigators with projects relevant to CDH.
Learn about the latest hypersomnia research on June 12th at the Hypersomnia Foundation’s regional conference, Beyond Sleepy in the Mile High City. Scientists will share findings from their recently completed clinical trials and other ongoing studies, lead us on a journey through the drug discovery and approval process, and help us to cope with the daily struggles of hypersomnia. You will also learn how your future participation in the registry can help to solve the puzzle of hypersomnia.
Tickets are running out so order your $25 ticket online to join us in person in Denver or wait until June 1 to sign up for a live Internet stream of the conference, brought to you free of charge through the generous support of Balance Therapeutics, Inc., and Flamel Technologies, SA.