Source: VB-CREATE

The cause of Parkinson's disease is named after the British surgeon James Parkinson. He is best known for his book An Essay on the Shaking Palsy - a clinical record of the disabling condition that causes dyskinesia. Parkinson's disease was first described as a neurological syndrome in 1817. However, as early as 1000 BC, ancient Indian and Chinese sources have recorded symptoms similar to Parkinson's disease.

Jean-Martin Charcot, the French neurologist who gave the disease its name, concluded that Parkinson's disease was different from other tremors, especially multiple sclerosis, because he found that not all Parkinson's patients had tremors.

Clinically, after a patient has been diagnosed with Parkinson's disease, therapeutic interventions need to be initiated. One of the most common drugs is Chalco's plant-based sedative hyoscyamine. This is an anticholinergic drug that blocks the action of the neurotransmitter acetylcholine in the central nervous system (CNS), used to control tremors and reduce muscle stiffness.

Then in the 20th century, with the introduction of the breakthrough drug levodopa, dopamine-based treatments also began to gain attention. As a temporary replacement for dopamine (dopamine levels drop in people with Parkinson's disease), levodopa is able to relieve movement disorders caused by the disease. But the drug's side effects are also of concern, and in addition to known symptoms such as nausea and dizziness, long-term use of the drug can also trigger movement disorders.

Over the years, with the increasing interest of deep brain stimulation in treatment research, surgery has also emerged as a viable treatment option for Parkinson's disease.

However, with Parkinson's disease affecting an estimated 10 million people worldwide and prevalence expected to double in the next 20 years, the need for treatment measures is currently unmet and researchers are working hard to find solutions.

Among some of the new treatments, here are five advances in Parkinson's disease research that could revolutionize treatment research.

#01

Focused ultrasound: a novel therapy for tremor in Parkinson's disease

Focused ultrasound technology is becoming a hot technology, and some recent developments have attracted the attention of the industry. Researchers at the University of North Carolina at Chapel Hill School of Medicine (UNC) led a clinical trial that demonstrated that focused ultrasound technology can improve movement disorders in patients with Parkinson's disease.

This therapy is designed to address involuntary movements that can occur in people with Parkinson's disease. These involuntary movements, which include twitching, twitching, twisting, or twisting of the face, arms, legs, or torso, are often seen in people with Parkinson's who take levodopa (an oral treatment that increases dopamine levels in the brain and reduces symptoms of the condition) for a long time.

In the trial, researchers at the University of North Carolina at Chapel Hill School of Medicine (UNC) evaluated 94 patients with Parkinson's disease and found that 75 percent of patients who received focused ultrasound therapy maintained positive outcomes for about a year after the treatment was completed. In addition to improving motor function and reducing involuntary movement, the therapy eliminates the risk of surgery, as the procedure requires no incisions.

Prior to this, common operations performed in patients with Parkinson's disease included thalamectomy and pallidectomy. These procedures can cause damage to a patient's thalamus or pallidum region, especially in patients who experience tremors (an involuntary movement that affects 80 percent of Parkinson's patients). Julie Pilitsis, a specialist in functional neurosurgery at the Marcus Neuroscience Institute in Florida, says these procedures cause damage to the brain by making an opening in the thalamus, making methods such as focused ultrasound all the more attractive.

"Instead of implanting something in the brain, focused ultrasound technology simply goes into a magnetic resonance device (MRI)... That means the patient won't need a craniotomy." Julie Pilitsis. "For older patients, I totally understand that they don't want to have surgery."

#02

Deep brain stimulation combined with therapy-based therapy has made progress in the treatment of Parkinson's disease

In 1997, deep electrical brain stimulation (DBS) began to be used to treat Parkinson's disease tremor. The method was approved in 2002 for the treatment of advanced symptoms of Parkinson's disease, and again in 2016 for the treatment of earlier symptoms, for those whose motor symptoms are completely controlled by medication. Recently, DBS has received a lot of attention due to its combination with stem cell therapy and gene therapy for Parkinson's disease.

Some studies have even considered using gene therapy in combination with DBS to replenish dopamine levels in the brain.

According to Julie Pilitsis, in the future, stem cell therapy and gene therapy seem promising for Parkinson's disease treatment.

"The technologies we see so far only include things like electricity or ultrasound. But these tools will become more and more advanced over time." Julie Pilitsis.

DBS works like a pacemaker by stimulating specific parts of the brain with implanted electrodes.

Julie Pilitsis explains the importance of fixed guides, which are designed to extend the function of DBS by inducing stimuli more precisely. "It's really very helpful because it's easier to program patients and reduce side effects." 'she said.

However, compared to traditional DBS leads, the positioning of the fixed lead is more challenging. Julie Pilitsis' current study will assess the extent of its effectiveness.

Meanwhile, researchers at the University of California, San Francisco and Ohio State University published a study in 2021 that looked at how the deficiency of aromatic L-amino acid decarboxylase (AADC) could be addressed through gene therapy. AADC is a rare genetic disorder characterized by insufficient synthesis of dopamine and serotonin.

The trial, which investigated the safety and efficacy of expressing AADC viral vectors, showed an increase in polyamine metabolism and a remission of ocular crisis movements (a condition that presents as spastic eye movements sometimes seen in Parkinson's disease and Parkinsonism) in seven child participants who received the therapy. Thus, the delivery of the gene carrier lacking in AADC is believed to be effective in enhancing motor function, indicating its potential to treat Parkinson's disease.

#03

New research finds a link between gut flora and Parkinson's disease

A University of Alabama study has found a link between gut flora and the onset of Parkinson's disease. The study, led by Haydeh Payami, a professor in the university's Department of Neurology, examined 257 species in the microbiome and concluded that 30 per cent were associated with Parkinson's disease.

"We found multiple mechanisms involved in Parkinson's disease, but we didn't know how they happened in the gut and which microbiome was responsible." "Payami said.

The researchers also observed a series of changes in the study: Parkinson's patients had a six-fold increase in the gut microbiota of bacteria like bifidobacterium, actinomyces caries, and Streptococcus mutans, while Clostridium Wexlerae and enterobacterium rosette significantly decreased.

Although the relationship between neurodegenerative diseases and the gut system has been previously demonstrated, this study provides a broader view of how the gut microbiota affects Parkinson's disease.

"This is exciting research because microbiome is an emerging but rapidly growing field, and although its resources, methods and tools are state-of-the-art, it is still developing." Payami said that in the future, more tools will be available to help probe the origins of Parkinson's disease and try to manipulate the microbiome to stop the progression of the condition.

#04

AbbVie drug candidate hits roadblocks, but could it be a blockbuster?

U.S. pharmaceutical company AbbVie's drug candidate ABBV-951, consisting of carbidopa and levodopa precursor drugs, has made waves for its potential ability to treat motor fluctuations in patients with advanced Parkinson's disease.

The drug received a complete Response letter (CRL) to a New Drug Application (NDA) from the U.S. Food and Drug Administration (FDA) in March 2023. Although this drug candidate has not yet been approved by the FDA, ABBV-951 was significantly effective in clinical trials compared to other levodopa drugs, and patients did not develop disease-plagued movement disorders.

The ABBV-951 drug candidate is designed to replace dopamine in the brain by continuous subcutaneous injections of carbidopa and levodopa over 24 hours, so the drug will be used to treat patients with a high need.

AbbVie plans to resubmit its application soon, and the drug candidate has been praised for its flexibility. According to Clarivate's Drugs of Concern 2023 report, ABBV-951 "may be an alternative for patients who do not qualify for DBS surgery or who do not wish to undergo surgery."

#05

Milestone, NADPARK trial shows improvement in NAD metabolism in Parkinson's patients

A new study led by Professor Charalampos Tzoulis of the University of Bergen has shown that oral niacin amide nucleoside (NR) can enhance NAD metabolism in patients with Parkinson's disease. The trial provides encouraging evidence for NR's treatment of Parkinson's disease.

The study, called NADPARK, aimed to determine whether the metabolism of NAD in the brains of people with Parkinson's disease could be enhanced by ingesting NR, an NAD precursor. NAD is a metabolic substance responsible for maintaining cell stability, which is often lacking in people with Parkinson's disease.

"We believe that enhancing the brain's NAD metabolism may improve a variety of symptoms unique to Parkinson's disease, such as mitochondrial dysfunction, DNA damage, epigenetic abnormalities and neuroinflammation." In addition, we speculate that NAD supplementation may also optimize neuronal metabolism and strengthen neurons, thereby making them more resistant to age-related stress and neurodegenerative diseases." "Tzoulis said.

Tzoulis said the results were "very encouraging" and pointed to NR as a "potential neuroprotective therapy for Parkinson's disease that deserves further investigation in larger trials."

To learn more about the extent to which NAD supplementation modulated Parkinson's disease progression, NOPARK is also conducting a Phase II study. Tzoulis said that if the trial is successful, it will be a step toward developing supervised drugs to treat Parkinson's disease.

"There are currently no treatments that can delay or stop the progression of Parkinson's disease. As a result, patients face progressive disability and early death. "If NAD supplementation proves to have neuroprotective and disease-modifying effects on Parkinson's disease, it will revolutionize the field and, for the first time, make an improved prognosis or even a cure possible for Parkinson's disease." "Tzoulis said.

"This is significant for patients, the scientific community and society as a whole."