Oct 1, 2026
By Simon Spichak, MSc Published On: September 14, 2026
Scientists are studying whether changes in gut bacteria and nerves might be the earliest signs of Parkinson’s.
Since constipation and other gastrointestinal symptoms may precede Parkinson’s by decades, researchers began to suspect that some cases of the disease originate in the gut.
Dr. Per Borghammer of Aarhus University Hospital pioneered the brain-first and body-first models of Parkinson’s, which aim to explain why some people develop different symptoms first. In the brain-first model, the disease starts in the brain’s smell center or its emotional hub and then spreads through to the regions that control motor movement. Others may experience a body-first form of the disease, where the first changes occur in the gut and then spread upward.
The body-first explanation is supported by research from Swedish and Danish health records. Individuals who received a surgery to cut part of the vagus nerve, one pathway through which scientists believe the disease may spread from gut nerves to the brain, had a slightly lower Parkinson’s risk.
Researchers are looking at gut bacteria and misfolded proteins called alpha-synuclein in the gut to untangle the relationship. While an exciting avenue of inquiry and promising data in animal models, these ideas still need confirmation in humans.
“If you just look at the evolution of the clinical symptoms of a patient, it fits pretty nicely,” with the idea that Parkinson’s may start in the gut for some individuals, Dr. Todd Levine, neurologist and chief medical officer of CND Life Sciences, told Being Patient. CND Life Sciences developed a skin-punch biopsy test which is used to measure misfolded proteins linked to Parkinson’s and other diseases.
Researchers hope that understanding these links may eventually lead to less invasive strategies to detect who’s at risk for the disease.
Sep 30, 2026
2 Sep 2026 - American Medical Journal - Author: Rana Zarour
Key Summary:
- Molecular net charge governs single-chain variable fragment solubility and stability in human cells.
- Deep learning redesign enables functional intrabody creation for sixty intracellular disease targets.
- Conformation-specific intrabodies successfully isolated pathological SOD1 and alpha-synuclein.
REPURPOSING antibody fragments for intracellular targeting gives clinicians new tools against neurodegenerative disease aggregates. While traditional monoclonal antibodies excel at binding extracellular antigens, single-chain variable fragments historically aggregate and rapidly lose functionality within the reducing cytoplasmic environment. Investigators resolved this persistent therapeutic bottleneck by establishing that whole-molecule net electrical charge serves as the primary determinant of intracellular solubility. Comprehensive analysis of more than one million paired variable domains demonstrated that natural antibody fragments are substantially more electropositive than native cytoplasmic human proteins. By engineering single-chain variable fragments to carry a net negative charge below minus fifteen through specialized interdomain linkers and terminal tags, investigators achieved intracellular solubility exceeding eighty percent without compromising baseline structural integrity.
Transforming the Antibody Interactome Through Inverse Folding
To expand this redesign strategy across the broader antibody interactome, researchers paired deep-learning inverse folding algorithms with precise structural constraints. Using ProteinMPNN alongside domain orientation rules, artificial intelligence systematically re-engineered variable framework regions to reduce surface positive charge while strictly protecting critical complementarity-determining regions and interface beta-sheets. This in silico platform yielded stable, highly soluble engineered intrabodies targeting sixty distinct intracellular proteins involved in oncologic and neurodegenerative pathways. The methodology reliably preserved parent antibody specificity across hundreds of constructs, generating validated candidates for targets such as p53, tau, ubiquitin carboxy-terminal hydrolase L1, and fused in sarcoma protein.
Sep 29, 2026
But some benefits were seen in analyses after end of brief, small program
Written by Michela Luciano, PhD | Sept. 23, 2026
- Anxiety is known to trigger or significantly worsen freezing of gait, or FOG, a symptom common in people with Parkinson’s.
- However, an intervention program that involved anti-anxiety coaching did not significantly cut FOG episodes in a small clinical trial.
- The researchers say further studies with more patients and longer intervention periods are needed to identify effective treatments for anxiety-related FOG.
A short, personalized intervention teaching people with Parkinson’s disease ways to manage anxiety that can trigger or worsen freezing of gait (FOG) — a common symptom in which individuals can not move their feet forward — did not significantly cut the number of such episodes when compared with no immediate treatment in a small clinical trial.
No differences were seen between participants who took part in weekly counseling sessions, spanning about one month, and those who did not, the researchers noted. The meetings with the neuropsychologist were aimed at helping patients to better understand the link between anxiety and FOG, and to develop strategies to prevent freezing.
Still, in exploratory analyses after all participants had received the four sessions, the scientists found evidence of reductions in time spent frozen, anxiety, and stress. However, because there was no longer a control group at that point, the team could not determine whether these improvements were due to the program.
“Contrary to our hypothesis, the intervention did not result in a greater reduction in FOG … compared to the control group,” the researchers wrote, noting, however, that the study was both small and limited in time.
“Future research is warranted to identify effective interventions for anxiety-related FOG in people with [Parkinson’s],” the team concluded.
The study, “‘Managing the mental state’ to tackle anxiety-related freezing of gait in people with Parkinson’s disease: a randomized controlled trial,” was published in the journal npj Parkinson’s Disease.
Problems with walking, and particularly freezing gait, are common and disabling Parkinson’s symptoms. FOG causes a person to suddenly become unable to step forward despite intending to walk — often described as feeling as if one’s feet are glued to the floor.
Episodes can occur when starting to walk, turning, doing another task while walking, or moving through narrow spaces. Anxiety can also trigger or worsen freezing, such as when someone feels rushed or worries about freezing in public.
“FOG has a profound impact on daily life and is a major risk factor for falls, underscoring the need for effective … therapeutic approaches,” the researchers wrote. Still, “treating FOG remains challenging, as symptoms are frequently resistant to both pharmacological and nonpharmacological interventions,” the team added.
Assessing whether strategies for anxiety can cut freezing of gait
Some people with Parkinson’s develop their own ways to manage FOG-related anxiety, such as using relaxation techniques and positive self-talk, or reducing the pressure of being rushed.
Collectively known as “Managing the Mental State” strategies, these are among the compensatory approaches that people with Parkinson’s report as particularly helpful for alleviating walking difficulties, including FOG, according to the researchers.
What works, however, can vary from person to person and situation to situation. For example, a strategy that helps an individual who freezes while rushing to answer the door may not help someone anxious about experiencing FOG in front of others.
Such variations “underscore the potential benefit of adopting a tailored approach that addresses FOG-related anxiety to treat [freezing episodes],” the researchers wrote. “So far, however, such tailored strategies have never been evaluated in a systematic manner.”
To evaluate the effectiveness of a personalized Managing the Mental State intervention for reducing anxiety-related FOG, researchers in the Netherlands and the U.K. focused on a program offering sessions with a trained neuropsychologist. The team conducted a randomized controlled trial, dubbed TACKLING-FOG (NCT06302309), that ran from April 2024 through September 2025.
The trial enrolled 41 people with Parkinson’s who experienced multiple daily freezing episodes that occurred or worsened with anxiety or stress.
Participants were randomly assigned to either receive the intervention immediately or spend four weeks on a waitlist before receiving it. The intervention group comprised 21 people, including 14 men, while 20 individuals — 12 of them men — were in the waitlist group. The participants’ ages were similar, with a mean age of 69.2 in the intervention group and 71.3 in the waitlist group.
Sep 28, 2026
It led to greater improvements than Tai Chi in balance, walking speed, and more
Written by Patricia Inácio, PhD | Sept. 25, 2026
- Parkinson's disease patients experience mobility limitations and gait difficulties that contribute to falls and a reduced quality of life.
- VR gait training improved several measures of mobility in Parkinson's more effectively than aquatic Tai Chi, a small trial found.
- Some of those advantages remained for another three months after training ended.
Both aquatic Tai Chi and virtual reality (VR) training improved walking, balance, mobility, and gait symmetry in people with Parkinson’s disease. However, VR training led to greater improvements in several measures and maintained some of these benefits three months after training ended, a small clinical trial found.
The study compared aquatic Tai Chi with training using the Computer Assisted Rehabilitation Environment (CAREN), an advanced virtual reality system that provides patients with visual cues and real-time feedback while they practice walking, over 12 weeks (about three months).
At the end of the 12-week intervention, participants using CAREN performed better across measures of Parkinson’s motor symptoms, balance, mobility, walking endurance, walking speed, and gait symmetry. Some of those advantages remained for another three months after training ended.
The study, “Effects of Aquatic Tai Chi and Computer Assisted Rehabilitation Environment-Based Virtual Reality Training on Rehabilitation in Patients with Parkinson Disease: A Randomized Controlled Trial,” was published in the journal Archives of Physical Medicine and Rehabilitation.
Gait difficulties impact quality of life in Parkinson’s
Parkinson’s disease is characterized by motor symptoms such as slowed movement, balance problems, and impaired walking. The disease is caused by the loss of dopamine-producing nerve cells, which release the neurotransmitter dopamine, a chemical messenger that enables nerve cells to communicate and, among other functions, helps regulate movement.
Gait difficulties are a major contributor to disability, falls, and reduced quality of life in Parkinson’s.
Although medications that replace or mimic the effects of dopamine are a cornerstone of Parkinson’s treatment, their long-term ability to control walking and balance problems is limited as the disease progresses. Exercise and rehabilitation, therefore, play an important role in maintaining mobility.
Tai Chi emphasizes controlled weight shifting, posture, and coordinated movement. Aquatic Tai Chi allows people to practice slow, controlled movements in water with less weight bearing.
VR-based training offers another rehabilitation approach aimed at improving balance, walking, and functional mobility. Computer-generated environments can provide visual cues and real-time feedback while patients practice walking tasks under controlled conditions. In Parkinson’s, this type of training may help compensate for difficulties with the automatic control and adaptation of walking.
CAREN is an advanced VR system that combines a treadmill and motion platform with visual feedback and changing simulated walking environments.
Sep 25, 2026
Study: OPTIMAL model shows promise for improving patient engagement
Written by Marisa Horak, MS | Sept. 17, 2026
- Parkinson's disease affects lung function and can lead to difficulty feeling motivated without help.
- It is important to incorporate strategies that enhance motivation in these patients during rehabilitation.
- Incorporating motivation-focused strategies significantly enhanced breathing performance.
Incorporating a theory focused on maximizing patients’ motivation may enhance the effectiveness of rehabilitation aimed at improving lung function in people with Parkinson’s disease, according to a new study.
“This study provides initial evidence that incorporating strategies [to maximize motivation] into respiratory training can enhance [lung function outcomes] in both healthy individuals and [people with Parkinson’s],” researchers wrote, adding that these findings “underscore the potential of motivational and attentional strategies to improve respiratory motor performance in respiratory tasks.”
The study, “Using the OPTIMAL Theory to Optimize Aerodynamics in Respiratory Training for Healthy Adults and Individuals With Parkinson’s Disease,” was published in the International Journal of Language and Communication Disorders.
OPTIMAL emphasizes participants’ expectations of improvement
Respiratory rehabilitation involves exercises that aim to strengthen the muscles responsible for pulling air in and out of the lungs. This type of therapy is commonly administered to help improve breathing ability among people with Parkinson’s.
When people are participating in any type of training, motivation plays a key role in how they perform. Motivation can be broadly conceptualized as either external — seeking to achieve something outside oneself, such as an award — or intrinsic, where the focus is on personal improvement and achievement.
A decade ago, researchers proposed a theoretical framework called Optimizing Performance Through Intrinsic Motivation and Attention for Learning, or OPTIMAL, that aims to maximize intrinsic motivation during rehabilitation. The theory emphasizes participants’ expectations of improvement, increases autonomy and choice, and directs focus toward the intended outcome rather than experiences within the body itself.
The OPTIMAL framework was originally developed for use during physical therapy aimed at strengthening the limbs. In this study, researchers wanted to see if the theory could also be applied to respiratory therapy in people with or without Parkinson’s. They noted that motivation-focused therapy may be especially useful for Parkinson’s patients because the disease’s effects on the brain often lead to difficulty feeling motivated without help.
Sep 24, 2026
by Chris Casey, CU Anschutz Medical Campus
edited by Lisa Lock, reviewed by Andrew Zinin
A woman began walking with a more fluid gait, while another patient could suddenly eat using utensils. Both patients, in advanced stages of Parkinson's disease, experienced immediate relief from severe tremor on one side of their body.
The technology behind these dramatic patient outcomes is a high-intensity focused ultrasound (HIFU) procedure that targets two tracts of the brain only a few millimeters—6 to 9, to be precise—apart.
The two recent treatments were performed by the Advanced Therapies in Movement Disorders (ATMD) Program at CU Anschutz. They were the first dual-target procedures using HIFU in the Rocky Mountain region.
Immediate symptom relief
The team leading the procedure included Drew Kern, MD, MS, associate professor of neurology, and Daniel Kramer, MD, associate professor of neurosurgery, both at the CU Anschutz School of Medicine. While the treatments provided immediate relief of motor symptoms for the two patients, further study is needed to determine HIFU's durability, potential cognitive effects and the merits of a bilateral treatment approach.
"We did it one week, and it worked great," Kern said of the dual-target procedure performed on the woman. "Then we thought about it for another patient—a man who had dementia. And sure enough, afterward he had zero rigidity and very little slowness of movement, plus no tremor. His wife said that was the best night of sleep they've had in years because he wasn't having a tremor. And, for the first time, he actually ate breakfast without any difficulty."
Dyskinesia, or involuntary movement, and bradykinesia, or slowness of movement, are among the motor complications affecting people with advanced Parkinson's disease. More than 1.2 million Americans have Parkinson's, a progressive neurological disorder with no cure.
Deep brain stimulation (DBS), in which surgeons implant electrodes in a targeted area of the brain, has been used to treat motor problems caused by Parkinson's disease for decades. In recent years, another therapeutic option, incisionless HIFU, has become available for patients with advanced Parkinson's who haven't found symptom relief from medications and aren't candidates for DBS due to infection risk and other reasons.
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