'America's Nobel' prizes go to sleep and hemophilia researchers, and to Michael J. Fox for Parkinson's advocacy

This year's Lasker Awards — coveted prizes for biomedical research that are sometimes called "America's Nobel Prizes" — have gone to scientists behind fundamental discoveries in sleep science and to researchers who developed a groundbreaking treatment for hemophilia.

Additionally, a Lasker Award for public service went to actor Michael J. Fox for his advocacy for patients with Parkinson's disease that has helped advance research into the neurodegenerative condition.

The prizes, each of which comes with an honorarium of $250,000, will be presented in person Sept. 17 in New York City. The awardees were announced Wednesday (Sept. 9) by the Lasker Foundation, which was established in 1942 by the philanthropists and health advocates Albert and Mary Lasker.

A deeper understanding of sleep

The first of the three awards, called the Albert Lasker Basic Medical Research Award, went to two scientists who independently discovered a key substance in the brain that helps control the sleep-wake cycle and is missing in people with some forms of narcolepsy — the neurological disorder marked by excessive daytime sleepiness and, sometimes, cataplexy (sudden episodes of muscle weakness).

The researchers — Dr. Emmanuel Mignot of the Stanford University School of Medicine and Masashi Yanagisawa of the University of Tsukuba in Japan — arrived at the discovery through different approaches. Mignot wanted to understand the underlying causes of narcolepsy, while Yanagisawa was investigating a curious class of receptors that were known as "orphans" because the chemicals that activated those receptors were unknown.

"We never thought we would end up in sleep," Yanagisawa told Live Science. "This was a kind of biochemical fishing expedition."

In particular, Yanagisawa was interested in proteins at the surface of cells called G protein-coupled receptors (GPCRs). When the right chemicals are plugged into these receptors, they trigger a chain of events within cells. Various compounds that activate GPCRs had already been found to be useful as drugs, but there were many receptors with unknown triggers.

Yanagisawa and colleagues went fishing for those triggering chemicals in rat brains, isolating substances called peptides from the tissue and then exposing GPCRs to those peptides. "We got very lucky, initially," Yanagisawa said. The fifth or sixth receptor they tested had a hit. Through further experiments, they landed on two closely related peptides as the trigger, and they found a second related receptor to match.

They discovered that the peptides came from a part of the brain called the hypothalamus, which was known to be involved in eating behaviors. So they named the peptides "orexins" after the Greek word for appetite, "orexis."

It turned out, though, that orexins' main job wasn't to control appetite; rather, they help promote wakefulness, the opposite of sleepiness. Mice without functional orexin genes would suddenly fall over and remain immobile for a minute or two, the researchers found. Peering into those mice's brains, they found that the animals were suddenly entering REM sleep, a phenomenon also seen in people with narcolepsy with cataplexy.

At the same time, Mignot, the other winner of the Lasker Award, was learning that orexin deficiency is also behind a form of narcolepsy seen in dogs. He then went on to study the mechanism in humans with narcolepsy.

"It became, suddenly, a very, very convincing story," Yanagisawa said of the researchers' converging findings. Previously, the study of sleep involved damaging parts of the brain and then seeing how a lab animal's sleep changed in response.

"There was no molecular level, genetic level, description of sleep regulation mechanisms at all," he said. "So our papers really shed new light on sleep regulation."

Together, the researchers' work paved the way to a new class of insomnia treatments, called orexin receptor antagonists, which promote sleepiness by turning down wakefulness. They have also led to new narcolepsy treatments called orexin receptor agonists, which boost wakefulness by increasing the receptors' activity. The first in the latter class of drugs was just approved in August.

A life-changing hemophilia treatment

The second award, called the Lasker~DeBakey Clinical Medical Research Award, went to three scientists affiliated with the Japanese drug manufacturer Chugai Pharmaceutical. These researchers — Kunihiro Hattori, Takehisa Kitazawa and Tomoyuki Igawa — created an antibody that interacts with key proteins in the blood that produce clots and thus stop bleeding.

This antibody treats hemophilia A, a severe bleeding disorder caused by a genetic mutation. That mutation causes the body to not make enough factor VIII, one of the key blood-clotting proteins. Normally, factor VIII grabs hold of two other clotting factors, and this enables a chain reaction that results in normal blood clotting. Without enough factor VIII, there is abnormal bleeding.

The severity of hemophilia A varies, but people with the disorder frequently experience blood pooling in their joints, which causes chronic pain and impairs mobility; they can also bleed uncontrollably even in the absence of trauma.

The antibody treatment works by binding two other clotting proteins — factors IX and X — to create a structure that fulfills the function of the missing factor VIII. Hattori, who is no longer at Chugai Pharmaceutical, initially launched the effort in 2000 after hatching the idea to use an antibody to bind several clotting factors together. Kitazawa and Igawa then brought the idea to fruition using pharmacology and chemical engineering, respectively.

The antibody, called emicizumab (marketed as Hemlibra), was approved by the U.S. Food and Drug Administration in 2017, and over 100 additional countries have approved the drug since. Over 30,000 people have received the antibody treatment to date, according to the award announcement.

Parkinson's disease advocacy

The third and final award — the Lasker~Bloomberg Public Service Award — went to Fox, actor and founder of The Michael J. Fox Foundation for Parkinson's Research.

Fox began experiencing symptoms of early-onset Parkinson's in 1990 at age 29. He publicly announced the diagnosis in 1998, sparking new discussions around the often-stigmatized disease. Through interactions with existing Parkinson's advocacy groups, Fox realized the field faced a lack of funding that likely hindered the pursuit of better treatments and a cure.

Since its inception in 2000, the foundation has funded more than $3 billion in Parkinson's research, according to the award announcement.

"When we launched the Foundation, our goal was simple, yet ambitious — cure Parkinson's," Fox said in a statement. "I am humbled to be recognized by the Lasker Foundation and jury. I accept this honor on behalf of everyone living with Parkinson's and everyone with us in our shared mission to end the disease."