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The Modag Anle138b Clinical Trial
Another neuroprotective approach involves enhancing cellular function, and significant preclinical research has shown that boosting the function of mitochondria can help cells survive. Mitochondria are the power stations of cells providing all of the energy requirements. Cure Parkinsons has several clinical trial programs dedicated to mitochondria-targeted approaches. An example of this is the UDCA in Parkinsons UP study. UDCA is a treatment that is used for dissolving gall stones, but recently researchers have found that it also has neuroprotective properties in models of Parkinsons. Cure Parkinsons is co-funding the UP study to determine if UDCA could be a useful neuroprotective treatment for Parkinsons.
Nerve Damage Seen In Skin Can Predict Parkinsons Progression
While the role of LRRK2 is not fully clear, a body of research suggests that its aberrant activation affects transit within cells, particularly the activity of lysosomes, subcellular compartments responsible for breaking down and recycling excess material and damaged cell parts. Abnormalities in lysosome activity may contribute to neurodegeneration.
BIIB122/DNL151, co-developed by Denali and Biogen, is a selective small molecule designed to cross the blood-brain barrier and block LRRK2 activity, specifically in the nervous system. The companies believe that doing so could restore lysosomal function and potentially slow Parkinsons progression. The blood-brain barrier, often called the BBB, is a highly selective membrane that shields the central nervous system from potential insults like viruses carried in the bloodstream.
The planned global trials the Phase 3 LIGHTHOUSE and the Phase 2b LUMA study will evaluate BIIB122/DNL151 in patients with and without LRRK2 mutations.
LIGHTHOUSE aims to enroll about 400 Parkinsons patients with LRRK2 mutations to test BIIB122/DNL151s effectiveness, with treatment running for at least 96 weeks . The LUMA Phase 2b study will recruit about 640 patients without LRRK2 mutations. This trial, designed to potentially support a request for BIIB122s regulatory approval, will dose selected participants for at least 48 weeks .
ROPAD, through tests given over two years, aims to identify 1,500 patients with LRRK2 mutations.
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Lets Talk Parkinsons Disease
Parkinsons is a slowly progressive disorder that affects movement, muscle control, and balance.
Our understanding of PD pathophysiology has vastly improved compared to what we knew 20 years ago, explained the study authors.
We believe we can be optimistic that the next 20 years will see major breakthroughs towards the discovery of therapies that may slow, stop, or reverse PD.
The authors summarise recent advances, including identification of the major genetic risks for Parkinsons disease, development of more representative animal models of the disease, early successes using Antisense Oligonucleotide and vaccination approaches in other neurodegenerative diseases, along with a translational pipeline of a broad range of repurposed drugs showing the first signals of potential efficacy, which are being driven forward through the various clinical trial stages.
Even A Little Exercise May Help Slow Parkinson’s
THURSDAY, Jan. 13, 2022 — A few hours of exercise a week may help slow Parkinson’s disease, even if it’s just moderate activity such as walking or gardening, a new study suggests.
The key is to be consistent, the researchers found.
“Although medications can provide people with Parkinson’s some symptom relief, they haven’t been shown to slow the progression of the disease,” said study author Dr. Kazuto Tsukita, of Kyoto University in Japan.
“We found that regular physical activity, including household tasks and moderate exercise, may actually improve the course of the disease over the long run,” he said. “Best of all, exercise is low-cost and has few side effects.”
Tsukita and his team assessed physical activity in 237 people with early-stage Parkinson’s. The participants were followed for up to six years.
While their activity levels at the outset did not affect the progression of their Parkinson’s, those who regularly got at least four hours a week of moderate to vigorous exercise during follow-up had slower declines in balance and walking ability than those who were less active.
The patients’ Parkinson’s symptoms were rated on a scale of 0 to 4, with higher scores indicating more severe symptoms, according to findings published online Jan. 12 in Neurology.
“Our results are exciting, because they suggest it may never be too late for someone with Parkinson’s to start an exercise program to improve the course of their disease,” Tsukita said in a journal news release.
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Research Supports What Many Neurologists Already Believe
Two hours twice per week of moderate exercise isnt a huge ask, not like going to the gym, which is difficult for many people with Parkinsons, notes Indu Subramanian, MD, a neurologist who treats patients with the condition at Ronald Reagan UCLA Medical Center in Los Angeles and who wasnt part of the Neurology study.
My colleagues and I have long believed that exercise is medicine in Parkinsons, but its exciting that these researchers found it may also improve brain function, says Dr. Subramanian.
Causes Of Parkinsons Disease
Parkinsons disease is caused by a loss of nerve cells in part of the brain called the substantia nigra, which leads to a reduction of dopamine in the brain. Dopamine plays a vital role in regulating the movement of the body. The exact cause of the loss of nerve cells is unclear. Most researchers think that a combination of genetic and environmental factors is responsible.
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Trials To Test Oral Biib122/dnl151 In Slowing Parkinsons Progression
Biogen and Denali Therapeutics are planning to launch two late-stage clinical trials to further evaluate the potential of their investigational oral therapy BIIB122/DNL151 in treating people with Parkinsons disease. The Phase 3 and Phase 2b trials, expected to commence this year, will be led by Biogen and follow…
Pilot Study Suggests Parkinsons Disease Progression Can Be Slowed
A pair of ultra-thin electrodes surgically implanted deep into the brain might slow the progression of Parkinsons disease, according to five-year outcomes from a 30-patient randomized clinical trial conducted by investigators at Vanderbilt University Medical Center.
Their report, published in the July 2020, issue of Neurology, presents the latest findings from the worlds first study of deep brain stimulation, or DBS, for early stage Parkinsons, defined as within four years of disease onset.
Parkinsons is a long-term neurodegenerative disorder most obviously characterized by tremor, rigidity, slow movement and difficulty with balance and walking. As of 2016, some 6.2 million people worldwide were living with Parkinsons. According to the Parkinsons Foundation, as many as 60,000 Americans are diagnosed each year with the disease.
From 2006 to 2009, the investigators enrolled 30 patients, all of whom received optimum drug therapy, with a random half additionally receiving DBS, which is often characterized as a pacemaker for the brain. In the DBS group, electrodes were positioned through two surgical openings in the cranium to deliver electric pulses to the subthalamic nucleus, a small cluster of neurons located deep within the brain on both sides. As with a heart pacemaker, the electric pulses are supplied by a battery implanted under the skin near the collarbone.
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Research Field: Proteins Central To The Development Of Parkinsons Disease
In a treatment room at the Parkinsons Clinic at Karolinska University Hospital, Svenningsson, who is a professor and neurologist, is talking to research nurse Lisa Hainke. They are working together in a clinical study, in which a new drug is being tested on patients with Parkinsons.
There are drugs that can inhibit early-stage symptoms, particularly motor function symptoms, but we cant slow down the progress of the disease. This new drug is a step in that direction, Svenningsson says.
Parkinsons disease is a neurological disease affecting the central or peripheral nervous system. Sufferers become slow, stiff and experience tremors. Many also suffer from depression and dementia. Age is the main risk factor. Svenningsson elaborates:
Most people develop the disease in their sixties, more men than women, but I also meet younger patients. By the time patients arrive at the clinic, they may have had symptoms for years without seeking or receiving help.
It often only takes Svenningsson a few seconds to see whether a patient has Parkinsons.
We do check for symptoms, but we also have the support of brain scans, which reveal whether the patient has reduced levels of dopamine, a neural transmitter, which plays a central role in the brains ability to control bodily movements.
Reprogramming For Compound Validation
Since their initial work focused on patients skin cells, the team needed to validate their findings in dopaminergic brain cells, which are lost in Parkinsons. This can be particularly challenging because we cant easily take a brain biopsy from a patient, says Dr Mortiboys. The team therefore used a reprogramming technique utilising the patients skin cells to generate induced neuronal progenitor cells. We used a slightly modified protocol, which doesnt take the cells all the way back to being stem cells, explains Dr Mortiboys. Our method takes them to an intermediate, which can only become brain cell types. Crucially for us, it doesnt take them back to the embryonic state. The reason for this is that age is one of the biggest risk factors for Parkinsons and many other neurodegenerative conditions. We didnt want to wipe all the age-associated changes in the cell so, with this reprogramming technique, we retained the changes that had happened throughout the cells lifetime while still producing a high percentage of dopaminergic cells.
Once these cells had been cultured, the team studied their mitochondrial function and observed that they were far more defective in the patients brain cells than in their skin cells. This showed us that it did matter which cells we were looking at it really was a problem with the mitochondria in the dopaminergic brain cells, explained Dr Mortiboys.
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Nasal Drugs Show Promise For Slowing Parkinsons Disease Progression In Lab Study
‘A remarkable advance’ if results can be replicated, Rush researcher says
Potential new treatments for Parkinsons disease developed by researchers at Rush University Medical Center have shown success in slowing progression of the disease in mice.
In a study published in Nature Communications, Rush researchers found that two different peptides helped slow the spread of alpha-synuclein, a protein that occurs in abnormal protein deposits called Lewy bodies in the brain. Lewy bodies are hallmarks of Parkinsons disease, the most common movement disorder affecting about 1.2 million people in the United States and Canada.
Currently, there are no treatments that slow the progression of Parkinsons disease they only treat the symptoms, says Kalipada Pahan, PhD, the Floyd A. Davis Professor of Neurology at Rush University Medical Center and a research career scientist at the Jesse Brown VA Medical Center, who led the study.
Lewy bodies are also associated with the development of Lewy body dementia and a rare neurological disorder called multiple system atrophy . At present, there is also no effective treatment for dementia with Lewy bodies and multiple system atrophy, Pahan says. Understanding how these diseases work is important to developing effective drugs that inhibit alpha-synuclein pathology, protect the brain, and stop the progression of Lewy body diseases.
Symptoms Of Parkinsons Disease
The main symptoms of Parkinsons disease are:
- Involuntary shaking of particular parts of the body
- Slow movement
- Stiff and inflexible muscles.
A person with Parkinsons disease can also experience a wide range of other physical and psychological symptoms. These include: depression and anxiety, balance problems, loss of sense of smell , problems sleeping , memory problems.
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Days Of Parkinsons: I Found Exercise To Be The Best Medicine
While medications are available to treat Parkinsons symptoms such as tremor and rigidity, none slow the diseases progression, which varies from patient to patient.
Past research has shown that exercise helps to ease motor and non-motor symptoms, with findings suggesting that at least two and a half hours of weekly exercise can slow decline and promote a better life quality. Mounting evidence also links physical activity to brain health, with regular exercise helping to delay brain aging and the onset of neurodegenerative disorders.
Were not suggesting that exercise will eliminate Parkinsons disease, but the results of SPARX2 signaled that exercise can slow the rate of disease progression, Cory Christiansen, PhD, principal investigator for the multisite SPARX3 trial at the University of Colorado , said in a press release.
Confirming through SPARX3 that high-intensity exercise works best to slow Parkinsons progression would give physicians more pointed guidance in advising patients.
Its easy to tell someone to exercise, but what kind of exercise? The study could offer clinicians the ability to be more precise in their prescription of exercise and the intensity, Christiansen said. And once youre dialed in as a patient, you dont really need to go to a physician to tell you to exercise. People will have the ability to be more in charge of their own health.
SPARX3 is due to conclude in July 2025.
Slowing Down The Progression Of Parkinsons Disease
We have all heard that keeping active is good for you and has immediate benefits for your health both short-term and long-term. Regular activity reduces the risk of developing some cancers, cardiovascular disease, as well as obesity and the health issues associated with this. What you may not have heard is regular exercise has also shown to slow the progression of Parkinsons disease.
Parkinsons disease is a neurodegenerative disease which targets and progressively damages nerve cells in a particular area of the brain over a long period of time. These nerve cells are very important for their role in producing a chemical called Dopamine. Without this chemical, the brain is not able to control normal bodily movement and the typical presentation of Parkinsons beings to show in the individual. This can range from balance issues, difficulty with memory and smell, as well as the well-known involuntary shaking. The cause of Parkinsons is still unclear, however, there is thought to be a combination of both genetic and environmental factors.
The link between exercise and reducing Parkinsons progression is believed to be focused on a particular protein known as the DJ-1 gene. As we all become more and more sedentary in our day-to-day lives, scientists have noticed an increase of a normal neural protein alpha-synuclein, which is important for relaying messages and normal brain function. However, in excessive clumps this could potentially be an issue.
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More Exercise Was Associated With Less Decline
Study participants who engaged in below-average levels of moderate to vigorous exercise, or less than one to two hours once or twice a week, saw their average symptom score increase from 1.4 to 3.7 over six years, the researchers said. In contrast, those who got above-average levels of moderate to vigorous exercise weekly saw their scores go from 1.4 to 3.0 during that same period.
On a cognitive test used in the study, which gave participants 90 seconds to match numbers with geometric figures and has a maximum possible score of 110, people with early-stage PD who engaged in less than 15.5 hours of work-type activity per week, on average, saw their scores fall from a 44 to 40 over the six-year study period, according to the researchers. Meanwhile, those who did more than 15.5 hours of work-related activities per week had drops in average scores from 44 to 43 over the same period, they said.
Still, the study doesnt prove that physical activity slows the progression of PD it merely shows the two are linked, the researchers said.
But it does expand on previous research suggesting the protective effects of exercise, including a study published in December 2021 in BMC Neurology, which showed that regular physical exercise was significantly associated with better cognition among 533 people with early-stage PD. But the BMC Neurology study was not able to specify the type and quantity of exercise needed to show a benefit.
Confirmed: No Slowing Of Parkinson’s Progression With Rasagiline
Erik Greb
A 1-mg daily dose of rasagiline has no disease-modifying effect for patients with Parkinson’s disease , new research confirms.
Results from a randomized, double-blind, placebo-controlled trial support previous observations that free-water accumulation in the posterior substantia nigra is a valid biomarker of disease progression.
However, at 1 year, pSN free-water accumulation was the same for the patients who received rasagiline and for those who received placebo.
Dr David Vaillancourt
“We’re using an imaging biomarker of the substantia nigra as the outcome variable, which has not been done before,” corresponding investigator David E. Vaillancourt, PhD, professor and chair of applied physiology and kinesiology at the University of Florida, Gainesville, Florida, told Medscape Medical News.
“We did not find evidence that rasagiline slows down the progression of the substantia nigra over time,” Vaillancourt said.
The findings were November 1 in Movement Disorders.
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Parkinsons Progression May Slow With Four Hours A Week Of Exercise Study Says
For people with early-stage Parkinsons disease, four hours a week of moderate exercise may help slow the progression of the disease. Symptoms of Parkinsons, which is a movement disorder, generally start gradually but worsen over time.
But research published in the journal Neurology found that those who were regularly active for at least that amount of time whether with traditional exercise or such physical activity as walking, gardening or dancing had less decline in balance and walking ability, were better able to maintain daily activities and did better on cognitive tests five years later than those who exercised less. The researchers noted that the key to achieving these benefits was maintaining regular exercise over time, rather than how active people had been when their disease started.
Parkinsons, which is more common in men than women, usually begins about age 60 as nerve cells in the brain become weak or damaged. Symptoms may include trembling or shaking , muscle stiffness , slow movement and poor balance and coordination. As symptoms get worse, people may have trouble walking, talking or continuing to do routine daily activities.
Linda Searing