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Revolutionary drug for schizophrenia wins US approval
The first schizophrenia medication in decades with a new mechanism of action won US regulatory approval today. The approval offers the hope of an antipsychotic that would be more effective and better tolerated than current therapies. The drug, known as KarXT, targets proteins in the brain called muscarinic receptors, which relay neurotransmitter signals between neurons and other cells. Activating these receptors dampens the release of the chemical dopamine, a nervous-system messenger that is central to the hallmark symptoms of schizophrenia, such as hallucinations and delusions.
Hope for tailored treatment
KarXT is just the first of many next-generation drug candidates designed to engage muscarinic receptors in the brain. Several follow-on schizophrenia therapies are already in or nearing clinical trials, showing promise for improved tolerability and more convenient dosing schedules.
This progress is leading clinicians and drug developers to imagine a future in which schizophrenia treatment becomes more tailored to individual needs — providing an alternative for the many people who don’t benefit from current therapies or abandon them owing to intolerable side effects.
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High price
The drug has a few shortcomings. For one, it requires twice-daily administration, and studies indicate that more frequent dosing schedules are linked to higher rates of non-adherence and treatment discontinuation in people with schizophrenia6. “That’s a big limitation,” says Nate Sutera, a psychiatric pharmacist at the University of Nebraska Medical Center in Omaha — particularly because many antipsychotics are now available as long-acting injectables, requiring only a few doses annually.
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Expensive but Valuable
Other drug makers are likewise seeing the value of targeting muscarinic receptors, pursuing various strategies to improve on the profile of KarXT. Some are developing formulations with more convenient dosing schedules. Others are focusing on greater target selectivity, aiming to design molecules that activate only specific muscarinic receptors — either the M1 receptor, linked to cognitive benefits, or the M4 receptor, which underpins antipsychotic effects, but not both, as KarXT does.
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Other Candidates - Cheaper?
One such drug candidate, an M4-selective agent called emraclidine, seems to have antipsychotic effects similar to those of KarXT, with improved tolerability. However, it offers potentially fewer cognitive benefits, according to early clinical testing.
Former Karuna chief executive Steven Paul, a psychiatrist now at the Washington University School of Medicine in St. Louis, Missouri, welcomes the wave of innovation in targeting muscarinic signalling that KarXT helped to unleash — and he looks forward to discovering the best ways to harness this therapeutic strategy.
Former Karuna chief executive Steven Paul, a psychiatrist now at the Washington University School of Medicine in St. Louis, Missouri, welcomes the wave of innovation in targeting muscarinic signalling that KarXT helped to unleash — and he looks forward to discovering the best ways to harness this therapeutic strategy.
Your diet can change your immune system
Physicians since Hippocrates have been exploring links between diet and health. In 1912, Polish biochemist Casimir Funk proposed that a lack of essential nutrients he called ‘vitamines’ was causing diseases including scurvy and rickets; later studies of vitamins confirmed their roles in immunity.
In the past decade, the greater availability of ‘omics’ techniques, which can catalogue and analyse entire sets of biomolecules such as genes and proteins in cells or tissues, has helped researchers to unpick the mechanisms by which different diets and dietary components affect the immune system, and therefore health.
If overeating and obesity harm health in multiple ways, could forgoing food have the opposite effect? And might the immune system play a key part here, too?
Evidence is building that fasting reduces the risks of a broad sweep of conditions, including hypertension, atherosclerosis, diabetes and asthma, in some cases through the immune system. For example, fasting has been shown to reduce the number of circulating monocytes, cells that defend the body against foreign invaders but that can be a hallmark of several autoimmune conditions.
Some researchers think that they can use such evidence to treat people with these conditions without them needing to eat less. For instance, Cheng Zhan, a neuroscientist at the University of Science and Technology of China in Hefei, wanted to investigate a group of neurons in the brainstem that helps to regulate the immune system, to see whether manipulating them could elicit the desired effect.
Confirming those clues in people can be difficult. Precisely controlling what study participants eat over long periods is challenging, as is getting them to accurately recall and record their diets each day. “One approach is to ask people to just eat the food you provide for them,” says integrative physiologist Kevin Hall at the US National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Maryland. “However, we know that when you do so, they consume 400 calories of off-study food on average.”
Belkaid acknowledges there is still much more work to do to unpick the effects of specific diets on the immune systems of those with different health conditions. However, she and Siracusa are among a growing group of immunologists who are optimistic that the mechanistic insights they and others are uncovering are the first steps towards personalized diets for a range of medical conditions. “I can imagine a world, in the next 10 years, in which we have access to rigorous dietary advice that can be applied in a range of clinical settings,” she says. “I think highly informed nutrition has enormous clinical potential.”
Masterplan for Life
1
Get Born
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2
Become Rich
Ut enim ad minim veniam, quis nostrud exercitation ullamco laboris nisi ut aliquip ex ea commodo consequat. Duis aute irure dolor in reprehenderit in voluptate velit esse cillum dolore eu fugiat nulla pariatur.
3
Die
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1000000 tonnes
That's how much a typical cloud weighs.
89 days
It took a man named Jeremy Harper to count to one million live (thus holding a World Record))
23,249,425 digits
Are in the largest prime number computed to this day - M77232917
Application process and requirements
Lunch and Dinner
Tomorrow
Your cellphone
A cold
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