2023年渴睡症 (發作性嗜睡症) 的新希望?

World's first drug research program to help narcolepsy sufferers

A trial in Sydney is underway on a drug that mimics the missing neurotransmitters that cause the debilitating sleep condition narcolepsy, opening the door to effective treatments.

The institute's professor, a sleep expert with more than 30 years of experience, said he has launched the world's first research program on orexin agonists, a class of drugs that stimulate the neurotransmitter orexin receptors. , which is absent or lacking in narcolepsy patients.

Narcolepsy (types 1 and 2) is a chronic condition that affects up to 6,000 Australians and is characterized by excessive daytime sleepiness, sleep paralysis, dreamlike hallucinations, automatic behaviors, and approximately 60 to 70% people develop narcolepsy. Sufferers have partial or complete loss of muscle control in response to emotions such as laughter.

Cataplexy, hallucinations, and sleep paralysis are all manifestations of REM sleep intruding into the waking state.

The mechanisms of the disease are poorly understood, but people with narcolepsy and cataplexy have low or undetectable levels of orexin in the fluid surrounding their brains.

Only a small group of neurons in the outer hypothalamus, the part of the brain that controls behaviors such as sleep, hunger, body temperature and arousal, produce orexin. In turn, these neurons project widely to brain centers that promote alertness. Orexin sends signals to other parts of the brain to prevent cataplexy, hallucinations and sleep paralysis.

In classic narcolepsy, orexin neurons degenerate or are lost entirely, meaning people with narcolepsy don't produce much or any orexin. In some other forms of severe sleepiness, there are problems with orexin neuron signaling.

The professor said: "Several companies are developing different orexin-based drugs, and preliminary studies have shown that these drugs have a remarkable ability to keep people with narcolepsy awake and productive. We are excited to be able to provide a new treatment for this dangerous and potentially dangerous drug . Affordable and effective treatments are available for the devastating disease. Narcolepsy causes people to fall asleep without their knowledge and can cause people to lose all muscle tone after experiencing strong emotions such as laughter, anger, etc. Additionally, There are many more people with other narcolepsy disorders related to problems with orexin transmission in the brain."

A recent phase 2 clinical trial of an oral orexin agonist (TAK-994) for the treatment of narcolepsy randomly assigned 73 patients to different doses of the drug or matching placebo for eight weeks. The professors, who wrote about the trial in a recent editorial for the New England Journal of Medicine (NEJM), argued that although the trial was stopped in October 2021 due to elevated liver enzymes, "reduction in large Efficacy Signal for Most Liver Enzymes” The narcolepsy aspect was particularly strong in the trial. "

They concluded, "Although development of TAK-994 has been discontinued, there is good reason to continue using orexin agonists to treat narcolepsy type 1 and perhaps other conditions, such as shift work sleep disorder or jet lag, Experiments are being carried out for this."

Recently participated in a global trial of the long-acting drug sodium oxybate, which is currently being launched in overseas countries as a first-line drug for the treatment of narcolepsy, which can improve sudden loss of muscle control (cataplexy) and help patients sleep at night.

Short-acting sodium oxybate is classified as a controlled substance in Australia and is only approved for use in special circumstances. It's also not covered by the Pharmaceutical Benefits Scheme, so it costs patients $15,000 to $22,000 a year, putting it out of reach for many.

The most urgent need is for patients with narcolepsy to have access to the best available medications.

The professor said despite Australia having a first-class health care system, the management of narcolepsy was significantly inadequate, leaving a group of people unable to work and with restricted lifestyles in many cases.

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