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Diabetes Medication Found to Slow Parkinson's Disease

written by hash brown taha Aug 26, 2024

Neurodegenerative disorders, including Alzheimer's disease and Parkinson's disease, pose a significant burden worldwide. These diseases impair both cognitive and motor functions, profoundly affecting millions. As healthcare improves, the number of affected individuals is expected to rise, increasing the emotional and financial strain on caregivers and medical systems. These conditions often require long-term, intensive care, which escalates the burden on family and community resources, highlighting the need for effective management strategies. Despite advances in medicine, no current drug can halt the progression of most neurodegenerative disorders due to the challenges posed by the brain's protective feature, the blood-brain barrier (BBB).

The BBB is a selective filter formed mainly by tightly joined cells. It protects the brain from potentially harmful substances in the blood, allowing essential nutrients to pass through. This selectivity, crucial for safeguarding the brain from toxins, significantly restricts drug delivery, making many potential treatments ineffective at directly targeting the brain's diseases.

Most drugs that might treat these brain diseases are either too large or do not possess the necessary properties to penetrate the BBB. This barrier is majorly fat-loving (lipophilic), which favors substances that dissolve in fats. Therefore, many drugs that could be effective are unable to reach the areas of the brain where they are needed. Neurologists often think of the brain as somewhat isolated when considering drug delivery. It is the significant reason why most preclinical studies focus on directly injecting the drug into the brain, sidestepping the BBB altogether

Additionally, neurodegenerative disorders are often marked by proteins in the brain that become abnormally sticky and clump together. These clumps lead to cellular dysfunction and contribute to the symptoms and progression of the diseases. Most clinical trials target these protein accumulations to clear or reduce their harmful effects. Unfortunately, many of these trials fail because the drugs used are not able to cross the BBB effectively.

A significant factor contributing to the failure of developing effective treatments for neurodegenerative disorders like PD lies in their localization within the most complex organ of the human body: the brain. These disorders are characterized by neurodegeneration, a process where brain cells progressively deteriorate and die, leading to the debilitating symptoms observed in these diseases.

However, researchers have begun investigating a new drug, Lixisenatide, initially designed to treat diabetes.

Repurposing Lixisenatide: A Potential Approach for Early Parkinson's

Lixisenatide is an interesting drug in the context of early Parkinson's disease treatment. Originally developed as a drug for type 2 diabetes, lixisenatide is a glucagon-like peptide-1 (GLP-1) receptor agonist. It stimulates insulin secretion and lowers blood sugar, but researchers have begun exploring its potential in neurodegenerative diseases like Parkinson's. Exploring lixisenatide and other GLP-1 receptor agonists for Parkinson’s is a prime example of drug repurposing—taking a drug approved for one condition and testing it for effectiveness in a different condition. This approach can save significant time and resources in drug development, especially when fast-tracking treatments for diseases like Parkinson's, where there is a substantial need for new therapeutic options.

The interest in lixisenatide for Parkinson's disease stems from its effects on several biological pathways that might influence neurodegeneration. Here is why:

  1. Neuroprotective Effects: GLP-1 receptor agonists like lixisenatide are believed to have neuroprotective properties. They may help reduce oxidative stress and inflammation in the brain, which are both factors that contribute to the progression of Parkinson's disease.
  2. Reducing Protein Aggregation: These drugs might also impact the handling of misfolded proteins in the brain, a vital issue in Parkinson’s. Enhancing cellular mechanisms for dealing with damaged proteins could potentially slow the development of pathologies associated with Parkinson’s disease. 

Promising View for Lixisenatide

From 2018 to 2020, a clinical trial investigated the effects of lixisenatide on persons with early Parkinson's disease. The study included 156 participants who were either given lixisenatide or a placebo (a non-active substance used as a control in testing new drugs). The study revealed several key findings:

  1. Short-Term Effectiveness: After one year, those who received lixisenatide showed slightly better scores on a test measuring motor skills (how well they moved) than those who received the placebo. The scores in the lixisenatide group slightly improved. In contrast, the scores in the placebo group worsened, suggesting that lixisenatide may help slow the progression of motor symptoms in early Parkinson's disease.
  2. Long-Term Effectiveness: Two months after stopping the medication (during a washout period), the lixisenatide group still maintained better motor scores than the placebo group, suggesting some lasting benefits.
  3. Attrition: Adherence to the treatment was high, with more than 92% of doses taken as prescribed, suggesting that the drug is tolerable by the participants.

The study suggests that lixisenatide could offer some benefits for controlling symptoms of Parkinson’s disease, although side effects and the need for dose adjustments are notable concerns. For instance, participants who took lixisenatide reported more side effects than those who took the placebo. Common side effects included nausea, vomiting, and gastroesophageal reflux (acid reflux). One serious side effect related to the treatment in the lixisenatide group was pancreatitis (inflammation of the pancreas).

These findings illustrate that drugs not initially designed for the brain could have significant benefits. This challenges the traditional view of the brain as an isolated organ and opens up possibilities for repurposing existing medications. However, to confirm these results and fully understand lixisenatide's potential for Parkinson’s disease, there is a clear need for multi-cohort studies that can provide more definitive answers and guide clinical applications.

 

Written by Hash Brown Taha

Edited By Saranyah Kannunchamy

 

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