The most effective way to tackle debilitating diseases is to punch them at the start and keep them from growing.
Research at Michigan State University, published in the Journal of Biological Chemistry, shows that a small “molecular tweezer” keeps proteins from clumping, or aggregating, the first step of neurological disorders such as Parkinson’s disease, Alzheimer’s disease and Huntington’s disease.
The results are pushing the promising molecule toward clinical trials and actually becoming a new drug, said Lisa Lapidus, MSU associate professor of physics and astronomy and co-author of the paper.
“By the time patients show symptoms and go to a doctor, aggregation already has a stronghold in their brains,” she said. “In the lab, however, we can see the first steps, at the very place where the drugs could be the most effective. This could be a strong model for fighting Parkinson’s and other diseases that involve neurotoxic aggregation.”
Lapidus’ lab uses lasers to study the speed of protein reconfiguration before aggregation, a technique Lapidus pioneered. Proteins are chains of amino acids that do most of the work in cells. Scientists understand protein structure, but they don’t know how they are built – a process known as folding.
Lapidus’ lab has shed light on the process by correlating the speed at which an unfolded protein changes shape, or reconfigures, with its tendency to clump or bind with other proteins. If reconfiguration is much faster or slower than the speed at which proteins bump into each other, aggregation is slow, but if reconfiguration is the same speed, aggregation is fast.
Srabasti Acharya, lead author and doctoral candidate in Lapidus’ lab, tested the molecule, CLR01, which was patented jointly by researchers at the University of Duisburg-Essen (Germany) and UCLA. CLR01 binds to the protein and prevents aggregation by speeding up reconfiguration. It’s like a claw that attaches to the amino acid lysine, which is part of the protein.
This work was preceded by Lapidus’ research involving the spice curcumin. While the spice molecules put the researchers on a solid path, the molecules weren’t viable drug candidates because they cannot cross the blood-brain barrier, or BBB, the filter that controls what chemicals reach the brain.
It’s the BBB, in fact, that disproves the notion that people should simply eat more spicy food to stave off Parkinson’s disease.
Spicy misconceptions notwithstanding, CLR01 mimics curcumin molecules’ ability to prevent aggregation. But unlike the spice, CLR01 can crossover the BBB and treat its targeted site. Not only do they go to the right place, but CLR01 molecules also work even better because they speed up reconfiguration even more than curcumin. Additionally Acharya showed that CLR01 slows the first step of aggregation, and the results from the study map out a clear road map for moving the drug to clinical trials.
Hearing about a nontraditional physics lab that was advancing medicine is what brought Acharya to work with Lapidus.
“I knew I wanted to study physics when I came to MSU, but when I heard Dr. Lapidus’ presentation during orientation, I knew this is what I wanted to do,” Acharya said. “We are using physics to better understand biology to help cure actual diseases.”
To help move the research to the next phase, Gal Bitan, co-author and professor at UCLA, is using crowdsourcing to raise funds for the clinical trials. Log on to the indiegogo.com website for more information.
The Latest on: Parkinson’s
via Google News
The Latest on: Parkinson’s
- What you need to know about Parkinson's Diseaseon December 2, 2019 at 8:03 am
One such disease is Parkinson's disease, or PD. The number of people with PD has steadily risen from approximately 7300 in 2006 to 10,700 in 2017 – and is expected to double in the next 25 years. This ...
- First-in-kind Human 3-dimensional Models of Parkinson’s Disease and Progressive Multiple Sclerosis Launching to the International Space Stationon December 2, 2019 at 7:54 am
The NSCF-funded collaboration between researchers at the NYSCF Research Institute and Aspen Neuroscience will perform the first study of long-term cell cultures of patient-derived induced pluripotent ...
- Parkinson's Disease Therapeutics- Global Market Outlook 2019 to 2025 | GSK, Novartis, Boehringer Ingelheim, Teva Pharmaceutical, Abbvie, Merckon December 2, 2019 at 6:04 am
Dec 02, 2019 (Market Insight Reports via COMTEX) -- Parkinson’s disease (PD) is a disorder of the nervous system that the increase in severity over time. The disease is characterized by bradykinesia, ...
- How a Child Taught Me to React When People Stare Because of Parkinson’s Diseaseon December 2, 2019 at 4:53 am
I remember one particular occasion vividly. It was when I had relatives visiting over Christmastime. My Parkinson’s disease was so bad I had to crawl out of my bedroom to go downstairs. This was ...
- Parkinson's: Ultrasound technology may relieve symptomson December 1, 2019 at 3:07 am
A new study shows that pulses of minimally invasive ultrasound waves improve the quality of life for people living with Parkinson's disease by immediately and significantly reducing tremors. Share on ...
- Increased Use of Antibiotics Linked to Greater Parkinson’s Riskon November 29, 2019 at 4:40 am
A new Finnish study suggests that greater use of antibiotics is linked to an increased risk for Parkinson’s disease. The strongest associations were found for broad spectrum antibiotics and those that ...
- Effect of Parkinson’s disease and related medications on the composition of the fecal bacterial microbiotaon November 29, 2019 at 2:17 am
In addition, previous studies also suggested that some PD medication may alter the microbiota composition. 20,21,22 L-dopa (L-3,4-Dihydroxyphenylalanine, levodopa) application targets the striatal ...
- Former Magic GM John Gabriel battles Parkinson’s on own terms: ‘I know what I got to do’on November 28, 2019 at 7:24 am
As John Gabriel lives a vibrant life with Parkinson’s disease, he can thank his family, friends and Larry David. Gabriel, who served as the Orlando Magic’s general manager from 1996-2004, is a fan of ...
- Deep brain stimulation for Parkinson's might disrupt swimming abilityon November 27, 2019 at 1:59 pm
A small study finds that some people lose their ability to swim when their Parkinson’s disease is treated with deep brain stimulation. Researchers identified nine cases of Parkinson’s patients who ...
- Deep Brain Stimulation May Put Parkinson's Patients at Risk for Drowningon November 27, 2019 at 1:08 pm
Swiss researchers identified nine Parkinson's disease patients who lost their ability to swim after receiving deep brain stimulation (DBS) of the subthalamic nucleus. All had been proficient swimmers ...
via Bing News