Exenatide Falls Short: What's Next for Parkinson's Breakthroughs?
Recently, we received the long-anticipated results from the Phase 3 Exenatide trial, which tested the diabetes drug exenatide (Bydureon) for Parkinson’s disease. Unfortunately, the trial did not achieve its primary goal of improving motor symptoms, leaving us with 14 clinical trials in Phase 3 for Parkinson's, only two of which target disease modification, with the remainder focused on symptom relief.
According to the “Hope List” compiled by Dr Kevin McFarthing, which tracks Parkinson’s research worldwide, only two other drugs remain in Phase 3 with the potential to disease modification: Annovis Bio's Buntanetap and Ambroxol, a repurposed over-the-counter cough medicine.. Although there are additional drugs in earlier phases (Phase 2 and 1), they remain years from completion. However, we hope to learn soon if these two disease-modifying treatments meet researchers' expectations and could eventually make a meaningful impact for people with Parkinson's.
What Happened with Exenatide?
The Exenatide-PD3 study showed no significant difference in the progression of symptoms between participants taking exenatide and those on a placebo. This trial, conducted in the UK with 194 participants over 96 weeks, tested the drug's ability to slow Parkinson's progression but did not produce the desired outcome.
What Are the Two Other Drugs in Phase 3?
Buntanetap
In July, new data from a Phase 3 trial revealed that buntanetap, developed by Annovis Bio, showed promising results in improving motor function in Parkinson's patients diagnosed more than three years ago and those experiencing balance and gait issues. After six months of daily treatment, the drug halted cognitive decline, even showing improvements in patients with mild dementia. Buntanetap works by reducing toxic protein clumps tied to neurodegenerative diseases, and the trial confirmed it as safe and well-tolerated.
Earlier, Phase 1/2 trial data laid the foundation for this Phase 3 trial, showing buntanetap's ability to outperform a placebo in enhancing cognitive and motor skills in Parkinson's patients while also reducing overall disease severity on the MDS-UPDRS scale. Additionally, treatment lowered levels of TDP-43, a harmful protein buildup similar to alpha-synuclein in Parkinson's. Based on this Phase 2 data, the FDA provided positive feedback on the company's plans to pursue a Phase 3 trial for buntanetap in patients with later-stage Parkinson's.
Ambroxol
The next announcement on the Phase 3 clinical trial of ambroxol as a treatment for Parkinson's disease is expected this autumn. Led by Professor Anthony Schapira at University College London (UCL), the trial has faced delays due to necessary drug reformulations and finalising contracts with research centers. This two-year, placebo-controlled study will involve 330 participants across 10-12 sites in the UK, with a focus on whether ambroxol can slow Parkinson's progression.
Ambroxol, commonly used as an over-the-counter cough medicine, has shown promise in early trials due to its potential to enhance the enzyme GCase, which aids in breaking down protein clumps associated with Parkinson's. In a Phase 2 trial, the drug increased GCase levels, reducing toxic protein buildup in cells, which is a known factor in Parkinson's neurodegeneration. If the ASPro-PD trial confirms that ambroxol can slow Parkinson's progression, there will be a concerted effort to make the treatment available as soon as possible.
More PD News Snapshots
Data from Landmark Michael J. Fox Foundation Study Shows Impact of Promising Parkinson's Therapy
In October 2024, Roche announced promising results for a new therapy, prasinezumab, which may help slow the progression of Parkinson's disease. Data from the Parkinson's Progression Markers Initiative, a long-term study by The Michael J. Fox Foundation, showed that patients treated with prasinezumab had at least 40% slower disease progression. This therapy targets a brain protein linked to Parkinson's and showed particular benefits for motor symptoms. To further explore its potential, Roche has launched the PADOVA trial with over 500 participants, bringing hope for new treatments and, eventually, a cure for Parkinson's.
New 24-Hour Parkinson's Treatment Approved by FDA: What You Need to Know About VYALEV
The FDA has approved VYALEV™, a new treatment for adults with advanced Parkinson's disease that provides continuous relief from motor symptoms for 24 hours through an under-the-skin infusion. This innovative medication combines levodopa and carbidopa, two common ingredients used to manage symptoms like tremors and stiffness, and it offers steady symptom control without the ups and downs associated with traditional oral medications. Designed for those who experience fluctuations in their symptoms, VYALEV™ has been shown in clinical trials to increase "on" time (periods of good movement) by an average of 2.72 hours without troublesome side effects. The treatment is delivered via a small pump, allowing for personalized dosing throughout the day and night. While it does have some mild to moderate side effects, VYALEV™ represents a significant advancement in managing Parkinson's disease and improving patients' quality of life.
Ophthalmic acid as an alternative to dopamine in motor control
A team at the University of California, Irvine, has discovered that a brain molecule called ophthalmic acid can act like dopamine in controlling movement, offering a promising new direction for treating Parkinson's disease. This molecule binds to calcium-sensing receptors, improving movement in Parkinson's mouse models for over 20 hours—far longer than the 2-3 hours typical of the current dopamine-based therapy, L-dopa, which also causes side effects with long-term use. This breakthrough suggests that dopamine isn't the only neurotransmitter managing movement and opens doors to treatments that could work through a previously unknown pathway. Researchers are now exploring ways to increase ophthalmic acid levels in the brain as a potential alternative therapy.
Cancer Drug Shows Promise in Blocking Harmful Protein Spread
Researchers have found a protein called Aplp1 that helps harmful proteins associated with Parkinson's disease spread in the brain. Interestingly, a cancer drug already approved by the FDA can block this process in mice by targeting a related protein called Lag3. When both proteins were blocked, the spread of these harmful proteins was reduced by 90%, potentially preventing damage to the brain cells responsible for movement. This suggests that the cancer drug could be repurposed to treat Parkinson's disease. The next steps involve testing this treatment on mouse models for Parkinson's and Alzheimer's, which could lead to new therapies to slow down these diseases.
High-intensity Exercise May Reverse Neurodegeneration in Parkinson's Disease
A recent small study suggests that intense exercise could not only slow down but might also reverse brain damage caused by Parkinson's disease. While earlier research showed exercise improves PD symptoms, this study is the first to demonstrate actual changes in the brain. Ten participants with PD completed a six-month high-intensity aerobic exercise program, and brain scans revealed healthier dopamine-producing cells that communicated better after the program. Dopamine is crucial for movement control, and these findings indicate that exercise may directly protect and repair brain cells rather than just treating symptoms like current medications do. This study highlights the importance of exercise in managing Parkinson's, suggesting it could have a more significant impact on brain health than previously thought.
$50M raised to advance brain stimulation device
Inbrain Neuroelectronics has raised $50 million to advance its brain-computer interface (BCI) technology, aiming to improve treatments for neurological conditions like Parkinson's disease. Using ultra-thin graphene electrodes, this BCI can adaptively stimulate specific brain areas based on real-time activity, aiming for better outcomes with fewer side effects than current deep brain stimulation (DBS) devices. The technology, recognized as a breakthrough device by the FDA, has shown promise in clinical trials and is also being tested for other conditions like epilepsy and brain cancer. Partnering with Merck KGaA and Imec, Inbrain plans to scale production and further its impact in neurology.
Cerevance's drug solengepras helps reduce off-time
In a recent trial, Cerevance's new oral drug, solengepras, showed promising results in improving the quality of life for people with Parkinson's by significantly reducing "off time"—the periods when symptoms like tremors and uncontrolled movements return despite medication. The Phase 2 trial included 141 patients who added solengepras to their standard Parkinson's treatments, with those on higher doses experiencing a reduction in off time by up to 1.6 hours, along with increased "on time" when symptoms were better managed. The drug also helped reduce sleepiness, was well tolerated with only mild side effects, and is currently being further tested in ongoing trials.
Right-Sided DBS: Effective Parkinson's Treatment Without Speech Loss
A recent study suggests that stimulating only the right side of the brain with deep brain stimulation (DBS) may help alleviate movement problems in Parkinson's disease without significantly impacting speech abilities. In contrast, left-side stimulation was associated with more noticeable speech difficulties. This finding indicates that unilateral DBS—stimulating just one side of the brain—could be a safer option than the traditional bilateral approach, which encourages both sides. Conducted by researchers at the University of Alabama at Birmingham, the study is part of the NIH's BRAIN Initiative and points to a promising, less invasive DBS approach that may help Parkinson's patients manage motor symptoms while preserving cognitive functions like speech.
Potential of Device-Assisted Therapy for Advanced-Stage Parkinson's Disease
At the 2024 International Congress of Parkinson's Disease and Movement Disorders (MDS), researchers presented promising results from the DIVE-I trial, a small study exploring a new device-assisted therapy for Parkinson's disease. The trial began in 2020 and included 12 patients experiencing movement issues. It also tested the safety and effectiveness of delivering dopamine directly to the brain via a small pump. This approach was found to control movement symptoms without causing dyskinesia, a common side effect of oral treatments. Dr. David Devos, co-founder of InBrain Pharma, highlighted the potential of this less invasive method to stabilize dopamine more effectively.
Parkinson's therapy Bemdaneprocel shows benefits for up to 2 years
Data from the Phase 1 exPDite trial of bemdaneprocel, a new cell therapy by Bluerock Therapeutics, showed promising results for Parkinson's disease. The therapy, which transplants dopamine-producing cells into the brain, helped patients experience more time with controlled motor symptoms ("on" time) and reduced "off" periods when medication is less effective. High-dose patients saw a 1.8-hour increase in on time and a 1.9-hour decrease in off time. Safe and well-tolerated up to 24 months post-surgery, even after stopping immune treatment, bemdaneprocel will now move to a Phase 2 trial for further study.
Department of Defense-funded research may lead to breakthroughs for Parkinson's neuropsychiatric symptom
Around half of people with Parkinson's disease (PD) experience neuropsychiatric symptoms like memory issues, sleep disruptions, depression, anxiety, and even hallucinations. Psychology professor Christopher R. Bishop and his team, supported by a four-year, $3 million Department of Defense grant, aim to uncover the causes behind these symptoms in PD patients. Their research, in collaboration with experts at Binghamton University, the Barrow Neurological Institute, and the University of Illinois, investigates how changes in serotonin-producing neurons contribute to these issues. They found that in Parkinson's, these neurons can start producing dopamine erratically when treated with L-DOPA, leading to serious side effects. This research seeks to pinpoint effective treatments, including existing medications, that could target serotonin-related challenges in PD. Their work highlights how Parkinson's impacts not only movement but also cognition, emotions, and sleep to enhance life quality for those affected.
New Data Demonstrate Substantial Therapeutic Potential of Capsida's IV Gene Therapy for Parkinson's Disease
Capsida Biotherapeutics has reported promising results for its gene therapy CAP-003, aimed at treating Parkinson's disease with GBA mutations (PD-GBA). Delivered via a simple IV, CAP-003 boosts levels of the GCase enzyme—deficient in many with this genetic mutation—by up to 250% in the brain's key areas, which is essential for brain health. Unlike other treatments, it also avoids side effects in the liver and other sensitive organs. With no safety concerns seen in animal studies, Capsida's CEO says CAP-003 could offer a safer, one-dose approach to slowing Parkinson's progression, with human trials expected in 2025.
New Parkinson's Drug VQ-101 Shows Promise in Early Human Trials
Vanqua Bio's experimental drug, VQ-101, shows promise as a treatment for Parkinson's disease based on early human studies. This oral medication activates an enzyme called glucocerebrosidase (GCase), which helps remove harmful protein clumps in the brain associated with the disease. In a Phase Ia trial, VQ-101 activated GCase by over 75%, exceeding expectations, and it was well tolerated by participants with no serious side effects. The drug successfully reached the brain, suggesting it could potentially slow or stop the progression of Parkinson's in future trials.
