Sleep apnea is a debilitating disease that many sufferers don’t even realize they have. Those afflicted with the condition will regularly stop breathing during sleep as the muscles in their throat relax, sometimes hundreds of times a night. Breathing eventually resumes when the individual’s oxygen supply gets critically low, and the body semi-wakes to restore proper respiration. The disruption to sleep causes serious fatigue and a wide range of other deleterious health effects.

Treatment for sleep apnea has traditionally involved pressurized respiration aids, mechanical devices, or invasive surgeries. However, researchers are now attempting to develop a new drug combination that could solve the problem with pharmaceuticals alone.

Breathe Into Me

There are a variety of conditions that fall under the sleep apnea umbrella, with various causes and a range of imperfect treatments. Perhaps the most visible is obstructive sleep apnea (OSA), in which the muscles in the throat relax during sleep. Under certain conditions, and depending on anatomy, this can lead the airway to become blocked, causing a cessation of breathing that requires the sufferer to wake to a certain degree to restore proper respiration. Since the 1980s, OSA has routinely been treated with the use of Continuous Positive Airway Pressure (CPAP) machines, which supply pressurized air to the face and throat to forcibly keep the airway open. These are effective, except for one major problem—a great deal of patients hate them, and compliance with treatment is remarkably poor. Some studies have shown up to 50% of patients give up on CPAP treatment within a year due to discomfort around sleeping with a pressurized air mask.

Against this backdrop, a simple pill-based treatment for sleep apnea is a remarkably attractive proposition. It would allow the treatment of the condition without the need for expensive, high-maintenance CPAP machines which a huge proportion of patients hate using in the first place. Such a treatment is now close to being a reality, under the name AD109.

The treatment aims to directly target the actual cause of obstructive sleep apnea. OSA is a neuromuscular condition, and one that only occurs during sleep—as those afflicted with the disease don’t suffer random airway blockages while awake. When sleep occurs, neurotransmitter levels like norepinephrine tend to decrease. This can can cause the upper airway muscles to excessively relax in sleep apnea sufferers, to the point that the airway blocks itself shut. AD109 tackles this issue with a combination of drugs—an antimuscarinic called aroxybutynin, and a norepinephrine reuptake inhibitor called atomoxetine. In simple terms, the aroxybutynin blocks so-called muscarinic receptors which decrease muscle tone in the upper airway. Meanwhile, the atomoxetine is believed to simultaneously improve muscle tone in the upper airway by maintaining higher activity in the hyperglossal motor neurons that control muscles in this area.

Thus far, clinical testing has been positive, suggesting the synergistic combination of drugs may be able to improve airflow for sleep apnea patients. Phase 1 and Phase 2 clinical trials have been conducted to verify the safety of the treatment, as well as its efficacy at treating the condition. Success in the trials was measured with the Apnea-Hypopnea Index (AHI), which records the number of airway disruptions an individual has per hour. AHI events were reduced by 45% in those taking AD109 when compared to the placebo group in a phase 2 trial featuring 211 participants. It achieved this while proving generally safe in early testing without causing detectable detriments to attention or memory. However, some side effects were noted with the drug—most specifically dry mouth, urinary hesitancy, and a level of insomina. The latter being particularly of note given the drug’s intention to improve sleep.

Testing on AD109 continues, with randomized Phase 3 trials measuring its performance in treating mild, moderate, and severe obstructive sleep apnea. For now, commercialization remains a ways down the road. And yet, for the first time, it appears promising that modern medicine will develop a simple drug-based treatment for a disease that leaves millions fatigued and exhausted every day. If it proves viable, expect it to become a major  pharmaceutical success story and the hottest new drug on the market.

For those born with certain types of congenital deafness, the cochlear implant has been a positive and enabling technology. It uses electronics to step in as a replacement for the biological ear that doesn’t quite function properly, and provides a useful, if imperfect, sense of hearing to its users.

New research has promised another potential solution for some sufferers of congenital deafness. Instead of a supportive device, a gene therapy is used to enable the biological ear to function more as it should. The result is that patients get their sense of hearing, not from a prosthetic, but from their own ears themselves.

New Therapy

There are a number of causes of congenital deafness, each of which presents in its own way. In the case of OTOF-related hearing loss, it comes down to a genetic change in a single critical protein. The otoferlin gene is responsible for making the protein of the same name, and this protein is critical for normal, functional hearing in humans. It’s responsible for enabling the communication of signals between the inner hair cells in the ear, and the auditory nerve which conducts these signals to the brain. However, in patients with a condition called autosomal recessive deafness 9, a non-functional variant of the otoferlin gene prevents the normal production of this protein. Without the proper protein available, the auditory nerve fails to receive the proper signals from the hair cells in the ear, and the result is profound deafness.

The typical treatment for this type of congenital hearing loss is the use of a cochlear implant. This is an electronic device that uses a microphone to pick up sound, and then translates it into electrical signals which are sent to electrodes embedded in the cochlear. These simulate the signals that would normally come from the ear itself, and provide a very useful sense of hearing to the user. However, quality and fidelity is strictly limited compared to a fully-functional human ear, and they do come with other drawbacks as is common with many prosthetic devices.

The better understanding that we now have of OTOF-related hearing loss presented an opportunity. If it were possible to get the right protein where it needed to be, it might be possible to enable hearing in what are otherwise properly-formed ears.

The treatment to do that job is called DB-OTO. It’s a virus-based gene therapy which is able to deliver a working version of the OTOF gene. It uses a non-pathogenic virus to carry the proper genetic code that produces the otoferlin protein. However, it’s no good if this gene is expressed in just any context. Thus, it’s paired with a special DNA sequence called a Myo15 promoter which ensures the gene is only expressed in cochlear hair cells that would normally express the otoferlin protein. Treatment involves delivering the viral gene therapy to one or both ears through a surgical procedure using a similar approach to implanting cochlear devices.

An early trial provided DB-OTO treatment to twelve patients, ranging in age from ten months to sixteen years. eleven out of twelve patients developed improved hearing within weeks of treatment with DB-OTO. Nine patients were able to achieve improvements to the point of no longer requiring cochlear implants and having viable natural hearing.

Six trial participants could perceive soft speech, and three could hear whispers, indicating a normal level of hearing sensitivity. Notably, hearing improvements were persistent and there were some signs of speech development in three patients in the study. The company behind the work, Regeneron, is also eager to take the learnings from its development and potentially apply it to other kinds of hearing loss from genetic causes.

DB-OTO remains an experimental treatment for now, but regulatory approvals are being pursued for its further use. It could yet prove to be a viable and effective treatment for a wide range of patients affected by this genetic issue. It’s just one of a number of emerging treatments that use viruses to deliver helpful genetic material when a patient’s own genes don’t quite function as desired.

While EEG research might help you figure out extrasensory perception, we won’t be betting on it. However, if you want to read EEG data and use an ESP32, [Cerelog-ESP-EEG] might be the right project for you. The commercial project is an 8-channel biosensing board suitable for EEG, EMG, ECG, and brain-computer interface studies. However, the company says, “We love the hacker community! We explicitly grant permission for Personal & Educational Use.” We love you too.

They do require you to agree not to sell boards you are building, and they give you schematics, but no PC board layout. That’s understandable, although we’d guess that achieving good results will require understanding how to lay out highly sensitive circuits.

What you do get is the schematic and the firmware source. They note that you may have to modify the firmware if you want to switch modes, change gain, or enable haptic feedback, among other things. At the application layer, the device is compatible with Lab Streaming Layer, and there is a fork of OpenBCI (brain control interface) that understands how to talk to the board.

Even if you don’t want to directly clone the device, there’s a ton of information here if you are interested in EEG or any other small signal acquisition. We’ve seen a number of interfaces like this, but we are still waiting to see a killer application.

As areas of uncontrolled cell growth, cancerous growth form a major problem for a multi-celled organism like us humans. Thus before they can begin to affect our long-term prospects of a continued existence, eradicating these cells-gone-wrong is essential. Unfortunately, doing so without affecting healthy cells significantly is tough. Treatments such as chemotherapy are correspondingly rough on the body, while radiation therapy is a lot more directed. Perhaps one of the more fascinating treatments involves ultrasound, with the IEEE Spectrum magazine recently covering one company providing histotripsy equipment.

Ultrasound has found many applications in the medical field far beyond imaging, with therapeutic ultrasound by itself covering a variety of methods to perform actions within the body without breaking the skin. By using high-energy ultrasound, everything from kidney stones to fat cells and cancerous cells can be accurately targeted and destroyed. For liver tumors the application of so-called histotropsy has become quite common, allowing certain types of tumors to be ablated non-invasively after which the body can handle the clean-up.

Histotropsy is a form of high-intensify focused ultrasound (HIFU) that uses either continuous or pulsed waves to achieve the desired effect, with the HIFU transducer equipped with an acoustic lens to establish a focal point. In the case of histotripsy cavitation is induced at this focal point that ends up destroying the local tissue. Beyond liver tumors the expectation is that other tumors will soon be treated in a similar manner, which could be good news for especially solid tumors.

Along with new approaches like CAR T cell immunotherapy, the prospects for cancer becoming a very treatable set of diseases would seem to be brighter than ever.