New drug may help reduce signs of motor deterioration in Parkinson’s

New drug may help reduce signs of motor deterioration in Parkinson’s

Jan 23, 2025

  • Prasinezumab, a monoclonal antibody designed to target protein clumps in the brains of people with rapidly progressing Parkinson’s disease, showed promise in reducing motor symptoms.
  • It’s the first experimental monoclonal antibody with such targeting, and a trial of 316 people suggests that it could be a path forward in fighting the disease.
  • However, experts say there are a number of questions that still need to be addressed through more rigorous clinical trials.

An experimental monoclonal antibody shows promise in reducing the motor skills deterioration of people with rapidly progressing Parkinson’s disease, a new study has revealed. The findings suggest that prasinezumab, which is designed to bind aggregated alpha-synuclein — a significant aspect of Parkinson’s that is thought to drive the progression of the disease — could have some positive effects on motor symptoms.

Parkinson’s is characterized by significant neurological decline that can manifest in tremors, motor control problems, and dementia. There is no known cause, but it is associated with a lack of dopamine in the brain. It is the second most common neurodegenerative diseaseTrusted Source after Alzheimer’s in the U.S., and it is believed that at least 500,000 adults in the U.S. have it.

The PASEDENA study, published in Nature MedicineTrusted Source, divided 316 people into three groups: 106 received 4,500 mg of prasinezumab, 105 received 1,500 mg, and 105 received a placebo.

The researchers had hypothesized that people with rapidly progressing Parkinson’s would respond the most to prasinezumab because the drug would provide a greater “signal-to-noise ratio,” meaning the degree of change over time would be easier to identify. 

They split the groups who took prasinezumab into several subpopulations with the following criteria:

After following all participants in the trial for 52 weeks, those who were taking prasinezumab had a greater reduction of motor skills deterioration than those taking the placebo.

A second phase of the PASEDENA trial is being conducted to examine how the drug can affect people with a slower progression of disease over a longer period of time, and a large phase 2 trial called PADOVA is looking further into populations with rapidly progression Parkinson’s.

Steve Allder, MD, consultant neurologist at Re:Cognition Health, who was not involved in the study, told Medical News Today that while the results are promising, there’s still a lot to examine in the wake of this initial study.

“This is really exciting research for PD. While the study on prasinezumab’s efficacy in Parkinson’s disease presents promising findings, some weaknesses warrant consideration including the study’s small sample size, limited treatment duration of 52 weeks and the highly variable disease progression among participants,” Allder said. 

“Addressing these limitations through larger, longer-term studies with diverse participant populations and comprehensive outcome measures is crucial for a more thorough evaluation of prasinezumab’s clinical utility in Parkinson’s disease management,” he added.

Targeting Lewy bodies in Parkinson’s

Monoclonal antibodies have not been traditionally used as a way to address Parkinson’s symptoms, Allder said, citing challenges in “effectively targeting its underlying mechanisms, particularly clumps of protein called alpha-synuclein aggregates.”

“Parkinson’s complexity, influenced by genetic and environmental factors makes it difficult to identify singular molecular targets to treat the disease,” he pointed out.

In the PASEDENA trial, prasinezumab was specifically designed to bind to those clumps of alpha-synuclein aggregates and help clear them from the brain. These clumps, known as Lewy bodies, are thought to have a significant role in advancing the disease by disrupting normal brain functions.

Challenges with monoclonal antibody therapy for Parkinson’s

But even with these positive results, there are hurdles to using monoclonal antibodies, Daniel Truong, MD, neurologist and medical director of the Truong Neuroscience Institute at MemorialCare Orange Coast Medical Center in Fountain Valley, CA and editor-in-chief of the Journal of Clinical Parkinsonism and Related Disorders, who was not involved in the study, told MNT.

“Their use as a tool to fight Parkinson’s disease is still in the investigational stage, and no monoclonal antibody therapy has yet been approved specifically for the treatment of PD,” Truong said.

“Parkinson’s disease is a complex neurodegenerative disorder with multiple underlying mechanisms, including the aggregation of alpha-synuclein, mitochondrial dysfunction, oxidative stress, neuroinflammation, and impaired protein clearance pathways. While alpha-synuclein aggregation is a hallmark feature, it is not the sole cause of PD pathology. Targeting alpha-synuclein alone may not be sufficient to halt or reverse the progression of the disease.”
— Daniel Truong, MD

Other issues that Truong pointed out include the general challenge of preparing clinical studies for monoclonal antibodies. These drugs have large molecular sizes that potentially prevent them from crossing the blood-brain barrier and the disease itself can vary from person to person.

“Parkinson’s disease is heterogeneous, with variability in symptoms, disease progression, and underlying pathology among individuals,” Truong said. 

“Subtypes of [Parkinson’s}, such as those characterized by predominant motor symptoms versus non-motor symptoms, may respond differently to treatment approaches. Personalized medicine approaches that consider individual variability in disease pathology and genetics may be necessary to optimize treatment outcomes,” he elaborated.

Can other treatments reduce motor skills deterioration in Parkinson’s?

Allder said there are several approaches that don’t involve monoclonal antibodies. While they don’t have the specific targeting that prasinezumab does, they can still adjust the chemical imbalances that contribute to disease progression, like a lack of dopamine.

“Deep brain stimulation uses implanted electrodes to adjust abnormal brain activity. Monoamine oxidase B (MAO-B) and catechol-O-methyltransferase (COMT) inhibitors help dopamine work better for longer,” Allder said. 

“Anticholinergic drugs ease tremors by blocking a brain chemical called acetylcholine, and glutamate modulators can help balance brain chemicals. New treatments that protect the brain are also being explored,” he added.

Truong said that further research is needed, given the small sample size and relatively short period of time that the PASEDENA trial covered.

“The findings of the study may not be generalizable to all individuals with Parkinson’s disease, as the study population may have specific characteristics or be enriched for certain subgroups (e.g., rapidly progressing early-stage Parkinson’s disease),” he added.

Written by Finn Cohen on April 25, 2024— Fact checked by Jill Seladi-Schulman, Ph.D.

Published by MedicalNewsToday.com

Novel drug molecule that helps recycle mitochondria may help treat Parkinson’s

Novel drug molecule that helps recycle mitochondria may help treat Parkinson’s

Jan 23, 2025

  • Researchers have found that a novel drug molecule may fight the development of early-onset Parkinson’s disease in younger people.
  • The new compound, BIO-2007817, is from the family of tetrahydropyrazolo-pyrazine (THPP) compounds.
  • It offered promising results in activating parkin, a key protein in the brain responsible for tagging damaged proteins in mitochondria.
  • Experts say the molecule’s ability to assist patients with early-onset Parkinson’s is promising, but more research is needed to establish a larger clinical application.

Researchers at McGill University in Montreal, Quebec, have found that a novel drug molecule may have the ability to fight the development of early-onset Parkinson’s disease in younger people, according to a new study published in Nature CommunicationsTrusted Source. 

The new compound is in the family of tetrahydropyrazolo-pyrazine (THPP) compounds developed by Biogen. The most successful such compound, referred to as BIO-2007817, can offer promising results activating parkin, a key protein in the brain responsible for tagging damaged proteins in mitochondria.

Mutations in parkin, often caused by genetic variation, can, in turn, result in damaged mitochondria, leading eventually to Parkinson’s disease. Parkin malfunction can also be caused by oxidative stress, environmental factors, and mitochondrial dysfunction.

Sreeganga Chandra, PhD, an associate professor of neurology and neuroscience at Yale School of Medicine, who was not involved in the study, told Medical News Today that these mutations in parkin can also be passed down to family members.

“Most Parkin mutations are inherited — so both parents are carriers. The mutations are due to DNA damage/improper repair etc. The Parkin mutations are recessive or loss-of-function. Parkin mutations impact a process called mitophagy which is the removal of damaged mitochondria. The issue is that damaged mitochondria ‘adulterate’ healthy mitochondria through fusion as well as cause oxidative damage.”
— Sreeganga Chandra, PhD

The study authors refer to BIO-2007817 as a type of “molecular glue” that activates parkin and may serve as a treatment for Parkinson’s. 

“Generalized activation of parkin is unlikely to be a viable therapeutic strategy due to parkin’s lack of substrate selectivity. As selective inducers, THPP compounds are promising leads for personalized medicine for patients with certain naturally occurring parkin mutations,” the authors write.

Can this molecule help reverse Parkinson’s disease?

Parkinson’s disease is a neurological condition that affects the nervous system and movement. Its symptoms occur because of low dopamine levels in the brain. Early signs include tremors, a loss of a sense of smell, and coordination problems.

Experts do not know whyTrusted Source Parkinson’s disease develops, but they currently believe that genetic changes and exposure to environmental factors, such as toxins, play a key role.

The symptoms of Parkinson’s disease develop gradually. They often start with a slight tremor in one hand and a feeling of stiffness in the body. Over time, other symptoms develop, and some people can experience dementia as a result of Parkinson’s.

Some early signs of Parkinson’s disease may include:

  • movement changes, such as tremors
  • coordination and balance impairments that can cause a person to drop things or fall over
  • a loss of sense of smell
  • gait changes, so a person leans forward slightly or shuffles when walking
  • fixed facial expressions due to changes in the nerves that control face muscles
  • a voice tremor or softer voice
  • more cramped and smaller handwriting
  • sleep problems resulting from restless legs and other factors
  • rapid eye movement sleep disorder may be a powerful predictor, according to a 2015 studyTrusted Source.

Daniel Truong, MD, neurologist and medical director of the Truong Neuroscience Institute at MemorialCare Orange Coast Medical Center in Fountain Valley, CA, and editor-in-chief of the Journal of Clinical Parkinsonism and Related Disorders, who was not involved in the study, told Medical News Today that the potential in this molecule is clear, but there are a number of concerns about how to apply it broadly.

“This enhanced parkin function allows for better removal of damaged mitochondria through mitophagy. Although the molecule doesn’t directly repair the initial mitochondrial damage, it helps mitigate further deterioration by restoring or increasing parkin activity. This can help clear damaged mitochondria more effectively, potentially slowing down disease progression before irreversible damage occurs,” Truong said. 

“While the findings around the molecule BIO-2007817 are promising, there are potential challenges and limitations such as the limitation of efficacy in advanced disease, the long-term effect, mutation specificity as it may work better with certain mutations but the broad effect is uncertain. These factors highlight the need for further research to determine the molecule’s broad clinical applicability,” he added.

How does early-onset Parkinson’s react differently to this treatment?

Truong told MNT that this “molecular glue” could be potentially effective in older Parkinson’s patients but may be more challenging than treating early-onset Parkinson’s.

“In older individuals, the accumulation of damaged mitochondria and cellular dysfunction is often more advanced. However, if this molecule can activate or restore parkin function, it could help remove damaged mitochondria even in later stages, potentially slowing disease progression and improving cell health. While it may not reverse extensive damage, it could offer symptom relief and slow further decline,” Truong said.

“There is a point in early-onset Parkinson’s disease (EOPD) where mitochondrial damage could become severe and potentially irreversible. Since parkin mutations impair the removal of damaged mitochondria, cells accumulate dysfunctional mitochondria over time, especially in neurons. Once the damage surpasses a certain threshold, cells may struggle to recover, even if parkin function is partially restored by treatments. However, therapeutic approaches targeting parkin activation, like those explored in this research, aim to intervene before reaching this critical point, potentially slowing or halting further damage.”
— Daniel Truong, MD

Written by Finn Cohen on October 1, 2024— Fact checked by Kevin Cyr, MD

Published by MedicalNewsToday.com