There is new hope for the treatment of ALS patients.
Prayagraj, 17 October: Significant progress has been made in the treatment of amyotrophic lateral sclerosis (ALS), often known as THE Lou Gehrig’s disease.
According to estimates, ALS is related with the death of motor nerve cells, or neurons, and affects three to five lakh people over the age of 50 in India each year, killing roughly 1.5 lakh people.
The study was conducted by Amit Dubey, a former Allahabad University scholar, in collaboration with experts from Shoolini University of Himachal Pradesh and Okinawa Institute of Science and Technology Graduate University in Japan.
There is currently no cure for ALS and no effective treatment to slow or stop the disease’s course.
The study’s findings have been published in the Royal Society of Chemistry’s (RSC) distinguished “New Journal of Chemistry”
However, fresh research by this team of researchers has revealed indications that “self-therapeutic gold nano-chaperon therapy” holds potential role in restoration of motor neuron processivity, which improves prospects of uncovering novel treatment options for motor neurone disease, also known as ALS.
The researchers discovered the pharmacological potential of a synthesised Gold-PEG (PolyEthylene Glycol — a petroleum-derived molecule with numerous applications) nanoconjugate in transgenic mice, as well as the mechanism through which it could aid in illness therapy.
“ALS is a rare and devastating neurodegenerative condition that affects voluntary muscle action and can result in paralysis or death.” ALS develops as a result of specific alterations that can be caused. by environmental variables such as smoking and pollutants, metals, or pesticides There is currently no cure for the condition. Patients’ only alternatives are two medications that assist manage the condition,” said Dubey, an AU alumna and major part of the study team.
“We reported in vitro restoration of motor neuron processivity following gold nano-chaperon therapy.” In transgenic mice, we tested the pharmacological potential of a synthesised Gold-PEG nanoconjugate. We discovered differences in the detection of the development of symptoms and the progression of the disease after Gold-PEG treatment when utilising behavioural tests like the rotarod and walking tests,” he noted.
According to Dubey, histology of the gastrocnemius muscle (big posterior muscle of the calf of the leg) revealed significant change in Gold-PEG administration
“The therapeutic potential of the nanoconjugate was discovered to be significant, with increased mouse survival and enhanced rotarod (spinning rod with forced motor activity applied) performance,” he stated.
According to new research, gold nanoparticles can extend the survival time of ALS mice by approximately seven days when compared to a control. Additionally, rotarod testing and other exams revealed significant improvements in the probability of commencement and the mean age at onset.
Gold-PEG-treated ALS animals also had less motor neuron degeneration, he added.
FAU researchers have discovered a protein with pathogenic characteristics.
There is currently no treatment for amyotrophic lateral sclerosis (ALS).
. However, things may be about to change. Researchers from FAU and the University of California, San Diego (UCSD) discovered a protein with pathogenic properties at an early stage of the neurological disease. The scientists reported their discovery in the journal “Acta Neuropathologica,” which could lead to a novel way to treating the disease.
A social media campaign in the summer of 2014 drew a lot of attention to amyotrophic lateral sclerosis, or ALS for short. In the ice bucket challenge, millions of people around the world emptied a bucket of ice cold water over their heads to mimic paralysis from the cold. There are roughly ALS affects 6,000 to 8,000 people, and around 2,000 new cases of the disease, which is fatal within a few years, are discovered each year. It has an impact on the nerve cells that control our muscles. Muscles start to deteriorate during the initial stage, making it impossible for patients to breathe or swallow on their own. societal media campaign was utilised to collect funds for ALS research. Reprogramming cells into stem cells to reset the biological clock
Beate Winner is an FAU professor for stem cell models for uncommon brain disorders, the chair of the Department of Stem Cell Biology, and a speaker for the Universitätsklinikum Erlangen’s Center for Rate Diseases. Her lab looks into what causes neurodegenerative
illnesses of the nervous system like ALS in the hopes of uncovering new therapeutic options. “We’ve known for almost 15 years that the protein TDP-43 located in neurons becomes insoluble and begins to form clumps towards the terminal stage of ALS,” Winner says.”It stops acting normally and has dangerous properties.” Even if these degenerative alterations in patients are not yet obvious, the fate of nerve cells remains unknown.
Reprogramming cells into stem cells to turn back the biological clock
Beate Winner is an FAU professor for stem cell models for uncommon brain illnesses, the chair of the Department of Stem Cell Biology, and a speaker for the Center for Rate Diseases at Universitätsklinikum Erlangen. Her laboratory explores what causes neurodegenerative illnesses of the nervous system such as ALS in the intention of uncovering new therapeutic options. Since approximately 15 years ago, researchers have understood that the neuronal protein TDP-43, which is normally soluble, starts to form clumps as ALS progresses. It fails. its normal functions and gains detrimental properties.” Although these degenerative alterations in patients are not yet obvious, the fate of nerve cells is.. is already closed. “We wanted to see if we could uncover causes for ALS at an early stage of development before the TDP-43 changes,” Winner explains.
She began her investigation alongside Prof. Dr. Jürgen Winkler and PD Dr. Martin Regensburger of the Universitätsklinikum Erlangen’s Department of Molecular Neurology. The researchers employed a novel method. They collected a small skin sample from the upper arm of ALS patients and healthy persons in a control group and reprogrammed it into induced pluripotent stem cells, which are akin to a very early stage of human development and can theoretically turn into any cell in the human body. These stem cells were subsequently reprogrammed to become nerve cells. “Essentially, we turned “We turned back the clock and created neurons that mimicked the embryonic stage of a foetus,” Winner adds. Shin’ya Yamanaka found that adult cells can be reprogrammed back into pluripotent stem cells, and he was awarded the Nobel Prize in Medicine for his work.
From an early stage, the protein NOVA1 has pathological characteristics.
Mass spectrometry, a high-throughput technique, was used by the Erlangen scientists to look for insoluble proteins in the cell samples. They were prosperous. An RNA-binding protein known as NOVA1 was found in the nerve cells of ALS patients. According to Dr. Florian Krach, a member of the FAU team and the study’s principal author, “In the neurons, the protein displayed modifications including a considerably elevated degree of insolvency, but not yet the typical pathogenic hallmarks of TDP-43.” “The control group’s cells did not show these alterations.”
With these discoveries in hand, Krach relocated to the lab of renowned RNA biologist and bioinformatics expert Prof. Gene Yeo at the University of California in San Diego (USA), supported by the California Technology Center in Bavaria (BaCaTeC). He was able to explore what NOVA1 binds to in RNA molecules and how it affects alternative splicing in human neurons through specialised tests and computer-assisted analyses. According to Krach, “Alternative splicing is an incredibly clever and sophisticated technique that humans use to
expand their repertoire of proteins.” Protein function is hampered, extended, or completely altered when sections of an RNA messenger molecule are either removed or inserted.
The researchers are hopeful that their findings may facilitate an early diagnosis and pave the way for fresh therapeutic ideas.
The uncontrolled nature of the alternative splicing process in ALS patients has long been recognised. TDP-43 is known to have an impact on this procedure. The scientists from Erlangen had a suspicion that other RNA-binding proteins, rather than TDP-43, were in charge of the pathogenic events in the early stages of the disease. The finding of NOVA1’s malfunctioning has now proven this suspicion to be correct.
Beate Winner states, “We have achieved a ground-breaking discovery, but it is simply one first step towards perhaps being able to diagnose ALS in the early stages. Before neurons reach the point of no return, the researchers hope that their findings will lead to the development of new therapeutic strategies.
