Latest news with #LRRK2
Yahoo
6 days ago
- Health
- Yahoo
Stanford scientists 'totally surprised' by potential Parkinson's treatment discovery
A recent study from Stanford Medicine that "totally surprised" researchers highlighted what could be a promising approach to slowing Parkinson's disease progression. The research, published in the journal Science Signaling, took a closer look at enzymes — proteins in the body that speed up chemical reactions and are essential for digestion, liver function and other key functions, according to Cleveland Clinic — and their role in Parkinson's. The team found that targeting a certain enzyme helped to restore neuron and cell communication in mice. Music Conductor With Parkinson's Sees Symptoms Improve With Deep Brain Stimulation Lead author Suzanne Pfeffer, PhD, the Emma Pfeiffer Merner Professor in Medical Sciences and a professor of biochemistry at Stanford, told Fox News Digital that the team was "totally surprised that we saw as much improvement as we did." In about 25% of Parkinson's cases, the culprit is some form of genetic mutation. One of the most common mutations creates an overactive enzyme called LRRK2, according to a Stanford press release. Read On The Fox News App When there is too much LRRK2 activity, it changes the structure of the brain cells, disrupting important communication between neurons and cells. This system is crucial to movement, motivation and decision-making, according to the researchers. The goal of the study was to determine whether a specific molecule — the MLi-2 LRRK2 kinase inhibitor — could reverse the effect of overactive enzymes. Parkinson's Patients Who Take 'Magic Mushrooms' See Key Benefits, Study Finds Using mice that had the genetic mutation that causes overactive LRRK2 and also had symptoms consistent with early Parkinson's disease, the scientists tried feeding them the inhibitor for two weeks. There were initially no changes detected in brain structure, signaling or function of the dopamine neurons. However, after three months of eating the inhibitor, mice affected by the overactive enzyme appeared to have restored their neurons to the point where they were virtually the same as those without the genetic mutation, the study found. "Findings from this study suggest that inhibiting the LRRK2 enzyme could stabilize the progression of symptoms if patients can be identified early enough," Pfeffer said in the press release. The study did have some limitations, the researchers acknowledged. "This was in mice, not people, but our current results indicate that similar pathways are important in humans," Pfeffer told Fox News Digital. While the study focused on a specific genetic form of the disease, overactive LRRK2 is also present in other cases, meaning this treatment could help multiple types of Parkinson's patients and possibly those with other neurodegenerative diseases, the reseachers claimed. Looking ahead, the team plans to investigate whether other forms of Parkinson's could benefit. Click Here To Sign Up For Our Health Newsletter Parkinson's — a disease that involves the slow death of dopamine-producing neurons, leading to symptoms like tremors and stiffness — affects nearly one million Americans, according to the Parkinson's Foundation, which has offices in New York and Miami. Experts agree that early intervention is key, as Parkinson's symptoms often appear years after the disease begins. Identifying and treating at-risk individuals sooner could potentially halt or reverse neuron loss. "These findings suggest that it might be possible to improve, not just stabilize, the condition of patients with Parkinson's disease," Pfeffer said. For more Health articles, visit The researcher told Fox News Digital that it's important to encourage patients to undergo genetic testing to learn more about their suitability for clinical trials and future treatments. The study was funded by The Michael J. Fox Foundation for Parkinson's Research, the Aligning Science Across Parkinson's initiative and the United Kingdom Medical Research article source: Stanford scientists 'totally surprised' by potential Parkinson's treatment discovery
Arabian Post
05-07-2025
- Health
- Arabian Post
Parkinson's Study Revives Hopes of Neuronal Recovery
A targeted drug therapy has shown potential to reverse cellular damage in Parkinson's disease by regenerating critical brain structures and restoring neuron function, according to new findings from a leading neuroscience research team. Scientists at Stanford University have demonstrated that suppressing the hyperactivity of a specific enzyme, LRRK2, with a compound called MLi-2 can prompt substantial recovery of dopaminergic signalling in a genetically engineered mouse model of Parkinson's. The treatment not only halted further degeneration but appeared to reverse structural impairments in the affected brain cells, marking a significant shift in understanding how Parkinson's progression might be modified at a cellular level. Parkinson's, a neurodegenerative condition marked by tremors, rigidity, and impaired movement, is primarily caused by the death of dopamine-producing neurons in the brain's substantia nigra. For decades, treatments have largely focused on symptom management rather than tackling the root causes of cellular dysfunction. The Stanford findings now suggest that correcting underlying molecular defects could pave the way for regenerative strategies. ADVERTISEMENT The breakthrough centres on the LRRK2 enzyme, mutations in which are among the most common genetic causes of Parkinson's. Overactive LRRK2 has been linked to damage of cellular structures called primary cilia — antenna-like projections that play a vital role in neuron communication and survival. The research team found that neurons in the striatum of the brain — a key region involved in motor control — lacked these cilia in the Parkinson's model mice. Using the LRRK2-inhibiting compound MLi-2, the team observed a significant regeneration of these lost cilia after three months of treatment. Dopamine signals began to function normally again in many of the affected neurons. The mice showed molecular signs of cellular recovery, with restored receptor localisation and improved intercellular communication. Importantly, the drug was administered after symptoms had started to appear, indicating that early-stage intervention could potentially reverse some aspects of the disease. Further investigations revealed that the repaired cilia helped restore the sonic hedgehog signalling pathway, which is essential for neuron protection and maintenance. In Parkinson's, reduced Shh signalling due to cilia loss contributes to further deterioration of neurons. Restoring this pathway through cilia regrowth suggests a dual benefit: halting ongoing degeneration and triggering repair mechanisms. Although the research was conducted on genetically modified mice, the implications for human forms of Parkinson's could be significant. LRRK2 mutations account for a relatively small percentage of all Parkinson's cases, but the pathway affected by this mutation may play a broader role in other forms of the disease, including idiopathic Parkinson's with unknown genetic causes. The MLi-2 compound itself is a highly selective, brain-penetrant molecule designed to inhibit LRRK2 activity without causing off-target effects. Previous efforts to target LRRK2 were hindered by concerns over safety and unintended consequences in other organs where the enzyme is also active. However, the current study found no major toxic effects over the duration of the experiment, opening the door for cautious optimism about its translational potential. ADVERTISEMENT Neuroscientists have long been searching for ways to go beyond dopamine replacement therapies, which offer temporary relief but do not prevent neuron loss. Deep brain stimulation and other invasive procedures are used in advanced cases but are not curative. A pharmacological approach that addresses root biological causes has remained elusive. The discovery that cellular antennae can regrow and restore critical signalling functions represents a conceptual leap in the field. Experts have noted that early intervention will be key. While the drug showed promise after symptoms appeared, the degree of neuronal recovery is likely to depend on how much degeneration has already taken place. Identifying Parkinson's earlier in its course, perhaps through biomarker detection, may significantly enhance the efficacy of such treatments. Further preclinical studies and safety evaluations are expected before MLi-2 or similar compounds move into human trials. Nonetheless, the research has sparked considerable interest among those exploring disease-modifying treatments. If replicated and expanded, the findings could contribute to a paradigm shift in the management of neurodegenerative conditions more broadly. The concept of regrowing cilia to restore function in damaged neurons could also have implications for other central nervous system disorders involving disrupted cell signalling. Beyond Parkinson's, researchers are already examining cilia dysfunction in conditions such as Alzheimer's and Huntington's disease.
Newsweek
01-07-2025
- Health
- Newsweek
Parkinson's Breakthrough Could Help Prevent Brain Cell Loss
Based on facts, either observed and verified firsthand by the reporter, or reported and verified from knowledgeable sources. Newsweek AI is in beta. Translations may contain inaccuracies—please refer to the original content. A new treatment for one type of Parkinson's disease may be on the horizon after researchers discovered a "brake" that can halt cell death. The study, led by researchers from Stanford University, California, involved a form of the neurodegenerative disorder that is caused by a single genetic mutation. This mutation causes an excess of a protein that interferes with the brain's ability to protect itself. Inhibiting this protein, the team found, can halt the damage and even allow dying neurons to recover. "These findings suggest that it might be possible to improve, not just stabilize, the condition of patients with Parkinson's disease," said paper author and Stanford biochemist professor Suzanne Pfeffer in a statement. Key, however, will be "if patients can be identified early enough," she added. While Parkinson's most recognizable symptom might be resting tremors, the earliest signs of the disease typically manifest some 15 years earlier. These first signs, Pfeffer said, include constipation, a loss of smell and REM sleep behavior disorder, a condition in which people act out their dreams while sleeping. Artist's impression of neurons in the brain. Artist's impression of neurons in the brain. FlashMovie/iStock / Getty Images Plus In the U.S, it is estimated that some 1.1 million people are living with Parkinson's disease—a figure only expected to rise in the near future, according to the Parkinson's Foundation. As Pfeffer and colleagues explain, around a quarter of all cases are caused by genetic mutations, with one of the most common being one that increases the activity of an enzyme called leucine-rich repeat kinase 2 (LRRK2). Too much LRRK2 in the brain changes the structure of cells by causing them to lose their "antenna" (technically the primary cilia) that allows them to send and receive chemical messages. In a healthy brain, communications are relayed back and forth between dopamine neurons in two regions of the brain known as the striatum and the substantia nigra. When dopamine neurons are stressed, they release a protein-based signal in the striatum called sonic hedgehog (after the video game character)—this causes neurons and support cells to produce so-called neuroprotective factors that shield other cells from dying. When LRRK2 activity crosses a certain threshold, the loss of the primary cilia in the cells of the striatum prevents them from receiving the sonic hedgehog signal; as a result, the neuroprotective factors are not produced. "Many kinds of processes necessary for cells to survive are regulated through cilia sending and receiving signals," explained Pfeffer. "The cells in the striatum that secrete neuroprotective factors in response to hedgehog signals also need hedgehog to survive. "We think that when cells have lost their cilia, they are also on the pathway to death because they need cilia to receive signals that keep them alive." A diagram shows how neurons (blue) rooted in the substantia nigra provide dopamine (dark green dots) to striatal neurons (red). A diagram shows how neurons (blue) rooted in the substantia nigra provide dopamine (dark green dots) to striatal neurons (red). Emily Moskal / Stanford Medicine It is possible to combat an excess of LRRK2 using a so-called "MLi-2 LRRK2 kinase inhibitor," a molecule that attaches to the enzyme and reduces its activity. In their study, Pfeffer and colleagues set out to test whether this inhibitor could also reverse the effects of too much LRRK2, as well as whether it was even possible for fully mature neurons and supportive glia to regrow lost cilia and regain their communication ability. At first, the results were not promising. The team gave the inhibitor for two weeks to mice that had the LRRK2 mutation (and show symptoms consistent with early Parkinson's disease)—to no effect. However, the researchers were inspired by recent studies into sleep-wake cycles, which found that the primary cilia on the mature cells involved grew and shrank every 12 hours. "The findings that other non-dividing cells grow cilia made us realize that it was theoretically possible for the inhibitor to work," said Pfeffer. Inspired by this, the team decided to try giving the mice the inhibitor for a longer time—with the results at three months being "astounding," the biochemist added. The longer treatment saw the percentage of striatal neurons and glia with primary cilia in the mice with the mutation increase to the same level as regular, healthy mice. This had the effect of restoring communication between the dopamine neurons and the striatum, leading to the normal secretion of neuroprotective factors. The researchers also found that the level of hedgehog signaling from the dopamine neurons decreased—suggesting that they were under less stress. Moreover, the density of dopamine nerve endings in the mice's striatum was found to double, suggesting that neurons which had been in the process of dying had recovered. LRRK2 inhibition decreased stress in dopamine neurons in mice models of Parkinson's (top right vs. bottom right—with healthy mice on the left for comparison.) LRRK2 inhibition decreased stress in dopamine neurons in mice models of Parkinson's (top right vs. bottom right—with healthy mice on the left for comparison.) Ebsy Jaimon & Suzanne Pfeffer With their initial study complete, the researchers say that their next step would be to determine whether other forms of Parkinson's that are not associated with the LRRK2 mutation could also benefit from the new treatment. This is possible, Pfeffer explains, because the mutation is not the only way to end up with an overactive LRRK2 enzyme. In fact, she added, the inhibitor treatment might even help with other neurodegenerative diseases. "We are so excited about these findings. They suggest this approach has great promise to help patients in terms of restoring neuronal activity in this brain circuit, said Pfeffer. She concluded: "There are multiple LRRK2 inhibitor clinical trials underway—and our hope is that these findings in mice will hold true for patients in the future." Do you have a tip on a health story that Newsweek should be covering? Do you have a question about Parkinson's disease? Let us know via health@ Reference Jaimon, E., Lin, Y.-E., Tonelli, F., Antico, O., Alessi, D. R., & Pfeffer, S. R. (2025). Restoration of striatal neuroprotective pathways by kinase inhibitor treatment of Parkinson's disease–linked LRRK2-mutant mice. Science Signaling, 18(793).
Yahoo
04-04-2025
- Health
- Yahoo
Arvinas' PROTAC halves protein suspected to play role in Parkinson's
A first-in-human trial of Arvinas' investigational Parkinson's' disease therapy, ARV-102, has been able to demonstrate a drop in the multifunctional protein that has been associated with the disease whilst also surpassing the blood-brain barrier. The Phase I single ascending dose (SAD) and multiple ascending dose (MAD) trial (EUCT-2023-507910-28-00) found ARV-102, a proteolysis targeting chimaera (PROTAC) therapy, led to a drop in leucine-rich repeat kinase 2 (LRRK2) across healthy volunteers. LRRK2 is associated with an increased risk of both autosomal dominant Parkinson's disease and Crohn's disease. In the SAD cohort, a single oral dose of at least 60mg of ARV-102, alongside further once daily repeated oral doses of at least 20mg, achieved greater than 50% LRRK2 reduction in the volunteer's cerebral spinal fluid. As well as a more than 90% LRRK2 reduction in the peripheral blood mononuclear cells (PBMCs). Investigation in the MAD cohort is still ongoing. Additional results from the SAD cohort found that ARV-102 at single doses of more than 30mg induced more than 50% decrease in peripheral phosphor-Rab10, a biomarker used to determine the therapy's ability to impact downstream of the blood-brain barrier. Noah Berkowitz, CMO at Arvinas, said: 'The ability of ARV-102 to cross the blood-brain barrier and degrade the LRRK2 protein offers a potentially transformative therapeutic approach in the treatment of devastating neurodegenerative diseases. 'We believe these results support continuing our ARV-102 clinical program and building upon our body of evidence for this lead PROTAC degrader candidate in our neuroscience pipeline.' Results from the randomised, double-blind, placebo-controlled were initially announced as part of the 2025 International Conference on Alzheimer's and Parkinson's Diseases (AD/PD) in Vienna, Austria. In the Phase I trial, the therapy was relatively well tolerated, with some adverse events (AEs) reported. Approximately 47 volunteers were recruited across all SAD dose levels with headaches reported in 17.1% of patients. Procedural pain associated with the lumbar puncture occurred in 28.6% of treated volunteers compared to 41.7% in placebo controls. This comes weeks after Arvinas' stock took a 51% after its PROTAC therapy for human epidermal growth factor receptor 2 (HER2) negative breast cancer therapy, being developed with pharma giant Pfizer, saw mixed results as it was only able to extend progression-free survival (PFS) in certain patients. The trial was conducted as part of a $2.4bn partnership between the companies. This latest Parkinson's data gives renewed hope to Arvinas for PROTAC therapies. Elsewhere in the field of Parkinson's disease therapies, Cerevance is continuing an ongoing pivotal study of its Parkinson's candidate despite it showing no benefit compared to placebo in a Phase II study. "Arvinas' PROTAC halves protein suspected to play role in Parkinson's" was originally created and published by Clinical Trials Arena, a GlobalData owned brand. The information on this site has been included in good faith for general informational purposes only. It is not intended to amount to advice on which you should rely, and we give no representation, warranty or guarantee, whether express or implied as to its accuracy or completeness. You must obtain professional or specialist advice before taking, or refraining from, any action on the basis of the content on our site. Sign in to access your portfolio
