from the world's big
Can Parkinson’s be prevented as it stealthily develops?
A new study finds it may take decades or even a whole lifetime to appear.
- Young Parkinson's disease patients may have just provided a vital clue for prevention.
- Misbehaving neurons that eventually produce the disease may be present at birth.
- A drug already on the market looks to be able to arrest Parkinson's progress.
Parkinson's disease comes with slowness, rigidity, tremors, and loss of balance due to an insufficiency of the dopamine that coordinates muscle movement. This disease, of which the rate of diagnosis is rising, occurs when the neurons responsible for producing dopamine malfunction or die. About 500,000 Americans are diagnosed with Parkinson's each year.
Most of the time, Parkinson's disease is a condition of the elderly, diagnosed in people 60 and older. However, about 10% of the time, it's detected in people between 21 and 50. "Young-onset Parkinson's is especially heartbreaking because it strikes people at the prime of life," says Michele Tagliati, an author of a new study from Cedars-Sinai.
The study of brain cells from Parkinson's younger victims has found that the misbehaving neurons are present long before diagnosis — typically taking some 20 or 30 years to produce detectable symptoms — and may even be present prior to birth. The revelation raises hope for combatting Parkinson's because there's already an approved drug that can mitigate the damage done by the troublemaking neurons before the disease ever appears.
The research is published in the journal Nature Medicine.
Looking at lab-made dopamine neurons
Image source: Kateryna Kon/Shutterstock
The authors' investigation began with an examination of neurons based on cells from young-onset Parkinson's (YOPD) patients who had no known mutations. From the cells, induced pluripotent stem cells (iPSCs) were generated and differentiated into dishes containing cultures of dopamine neurons. Senior study author Clive Svendsen says, "Our technique gave us a window back in time to see how well the dopamine neurons might have functioned from the very start of a patient's life."
The scientists observed lysosomes within the YOPD neurons malfunctioning. Since lysosomes are counted on as "trash cans" for unnecessary or depleted proteins, the castoff chemicals began to pile up. In particular, substantial accumulations of soluble α-synuclein, a protein implicated in different types of Parkinson's, were seen.
Says Svendsen, "What we are seeing using this new model are the very first signs of young-onset Parkinson's,"revealing that, "It appears that dopamine neurons in these individuals may continue to mishandle α-synuclein over a period of 20 or 30 years, causing Parkinson's symptoms to emerge."
The researchers also saw unexpectedly high levels of the enzyme protein kinase C in its active form, though what that has to do with Parkinson's, if anything, is unknown.
Image source: sruilk/Shutterstock
The researchers tested a number of drugs on the cultures to see if any might address the observed accumulations of α-synuclein. (They performed parallel tests of laboratory mice.) One drug, PEP005, which is already approved by the FDA for treating skin pre-cancers, did effectively reduce the α-synuclein buildup, both in the iPSCs and the mice.
Since PEP005 is currently administered in gel form for treating skin, the researchers are now exploring how the drug might be modified so it can be delivered directly to the brain. The team also plans follow-on research to see if their findings apply equally to forms of Parkinson's beyond YOPD.
Andy Samberg and Cristin Milioti get stuck in an infinite wedding time loop.
- Two wedding guests discover they're trapped in an infinite time loop, waking up in Palm Springs over and over and over.
- As the reality of their situation sets in, Nyles and Sarah decide to enjoy the repetitive awakenings.
- The film is perfectly timed for a world sheltering at home during a pandemic.
China moves to Russia and India takes over Canada. The Swiss get Bangladesh, the Bangladeshi India. And the U.S.? It stays where it is.
What if the world were rearranged so that the inhabitants of the country with the largest population would move to the country with the largest area? And the second-largest population would migrate to the second-largest country, and so on?
A recent analysis of a 76-million-year-old Centrosaurus apertus fibula confirmed that dinosaurs suffered from cancer, too.
- The fibula was originally discovered in 1989, though at the time scientists believed the damaged bone had been fractured.
- After reanalyzing the bone, and comparing it with fibulas from a human and another dinosaur, a team of scientists confirmed that the dinosaur suffered from the bone cancer osteosarcoma.
- The study shows how modern techniques can help scientists learn about the ancient origins of diseases.
Centrosaurus apertus fibula
Royal Ontario Museum<p>In the recent study, the team used a combination of techniques to analyze the fibula, including taking CT scans, casting the bone and studying thin slices of it under a microscope. The analysis suggested that the dinosaur likely suffered from osteosarcoma, a type of bone cancer that affects modern humans, typically young adults.</p><p>For further evidence, the team compared the damaged fibula to a healthy fibula from a dinosaur of the same species, and also to a fibula that belonged to a 19-year-old human who suffered from osteosarcoma. Both comparisons supported the osteosarcoma diagnosis.</p>
Evans et al.<p style="margin-left: 20px;">"The shin bone shows aggressive cancer at an advanced stage," Evans said in a <a href="https://www.rom.on.ca/en/about-us/newsroom/press-releases/rare-malignant-cancer-diagnosed-in-a-dinosaur" target="_blank">press release</a>. "The cancer would have had crippling effects on the individual and made it very vulnerable to the formidable tyrannosaur predators of the time."</p><p style="margin-left: 20px;">"The fact that this plant-eating dinosaur lived in a large, protective herd may have allowed it to survive longer than it normally would have with such a devastating disease."</p><p>The fossilized fibula was originally unearthed in a bonebed alongside the remains of dozens of other <em>Centrosaurus </em><em>apertus</em>, suggesting the dinosaur didn't die from cancer, but from a flood that swept it away with its herd.</p>
Dinosaur fibula; the tumor mass is depicted in yellow.
Royal Ontario Museum/McMaster University<p>The new study highlights how modern techniques can help scientists learn more about the evolutionary origins of modern diseases, like cancer. It also shows that dinosaurs suffered through some of the same terrestrial afflictions humans face today.</p><p style="margin-left: 20px;">"Dinosaurs can seem like mythical creatures, but they were living, breathing animals that suffered through horrible injuries and diseases," Evans said, "and this discovery certainly makes them more real and helps bring them to life in that respect."</p>
Join the lauded author of Range in conversation with best-selling author and poker pro Maria Konnikova!
UPDATE: Unfortunately, Malcolm Gladwell was not able to make the live stream due to scheduling issues. Fortunately, David Epstein was able to jump in at a moment's notice. We hope you enjoy this great yet unexpected episode of Big Think Live. Our thanks to David and Maria for helping us deliver a show, it is much appreciated.