Two novel intranasal medications have reduced inflammation and inhibited the spread of alpha-synuclein in Parkinson’s disease in mice models
BY DR WAEL MY MOHAMED
MOST Parkinson’s disease patients report a reduced sense of smell, which begins many years before other symptoms manifest.
Researchers are investigating whether scent-processing neurons that connect the nose to the brain have a role in Parkinson’s disease progression. Over 80 per cent of persons with Parkinson’s disease have a diminished sense of smell, which frequently manifests years before the beginning of typical movement-related symptoms.
While existing medicines can help control some of the symptoms of Parkinson’s disease, we cannot halt or even slow its progression. Researchers investigated potential relationships between environmental exposures in the nasal cavity, inflammation, odour processing centres in the brain, and Parkinson’s-related genes in both animal models and humans.
The researchers investigated the possibility that some environmental triggers, such as viruses, might initiate a chain reaction in the nose’s odour-sensing cells, culminating in creating clumps of a protein called alpha-synuclein. If this is the case, scientists hypothesise that this process might eventually spread across the brain via connections, thus encouraging Parkinson’s disease, particularly in those with several risk factors for the condition.
If Parkinson’s disease does begin in the nasal cavity, early symptoms of the condition may be detectable in nasal secretions. Such a fluid-based biomarker would be helpful for Parkinson’s disease diagnosis and monitoring, as well as clinical trials of novel medicines.
Nasal drugs show promise in slowing progression
Researchers at Rush University Medical Center have demonstrated results in halting the course of Parkinson’s disease in rats. Two novel intranasal medications reduced inflammation and inhibited the spread of alpha-synuclein in Parkinson’s disease in mice models. Additionally, the medicine enhanced the animals’ gait and balance. If the findings are duplicated in people, the medications might be heralded as a “dramatic advance” in the treatment of Parkinson’s disease, the researchers believe.
Rush University researchers discovered that two distinct peptides (chains of amino acids) slowed the spread of alpha-synuclein, a protein prevalent in aberrant protein deposits termed Lewy bodies in the brain. Parkinson’s disease, the most prevalent movement illness affecting around 1.2 million individuals in the United States and Canada, is characterised by Lewy bodies.
Now, no medication exists that slows the course of Parkinson’s disease – they simply address the symptoms. The study used laboratory-developed peptides known as TLR2-interacting domain of Myd88 (TIDM) and NEMO-binding domain (NBD).
The medications were shown to reduce inflammation in the brain and halt the spread of alpha-synuclein in animals with Parkinson’s disease when administered by the nose. Additionally, the therapies enhanced the mice’s walking, balance, and other motor abilities. If these findings are duplicated in people, it will represent a significant step forward in treating debilitating neurological illnesses.
Therapy is delivered straight to the brain.
A novel gel containing levodopa has been shown to attach to nasal tissue. The gel rapidly releases levodopa into the bloodstream and brain. According to the researchers, preliminary evidence indicates that the gel is successful in animal models.
The University of York’s scientists has made significant progress in developing a nasal spray medication for Parkinson’s disease sufferers. Researchers have discovered a novel gel that, when combined with the medicine levodopa, may stick to tissue inside the nose, assisting in delivering therapy straight to the brain.
Levodopa is converted in the brain to dopamine, which compensates for the absence of dopamine-producing cells in Parkinson’s disease patients and aids in treating the illness’s symptoms. However, over extended periods, levodopa becomes less effective, and larger dosages are needed.
The existing treatment for Parkinson’s disease is helpful, but with prolonged usage, the medicine is broken down before it reaches the brain, where it is most required. This necessitates an increase in dose, and in later phases, the medicine may need to be injected rather than taken as pills.
Nasal sprays have long been investigated as a more effective delivery method due to their direct path to the brain via the nerves that supply the nose. Still, the problem here is to discover a means to make them cling to the nasal tissue long enough to provide an adequate dose of the medicine.
Increasing brain absorption
The researchers developed a levodopa-loaded gel that could flow into the nose as a liquid and then swiftly transform into a thin coating of gel. A team from King’s College London validated the approach in animal models, demonstrating that levodopa was successfully released from the gel into the bloodstream and straight into the brain.
The team is now developing nasal spray devices with these materials to advance to human clinical trials. Additionally, the method may apply to other neurodegenerative disorders such as Alzheimer’s disease.
Not only did the gel outperform a simple solution, but it also had a higher brain absorption than the medicine administered by intravenous injection. This shows that nasal administration of Parkinson’s disease medications via this gel form may have therapeutic use.
Thus, this method is being evaluated as a vehicle for the nasal administration of neuroactive drugs. This technique has the potential to circumvent first-pass liver metabolism and traverse the blood-brain barrier, thereby increasing brain absorption.
Biocompatibility experiments in vitro reveal that the gel is biocompatible with nasal epithelial cells. This is due to the gel’s prolonged residence time in the nasal cavity, which results in higher blood and brain concentrations.
It is demonstrated that intranasally delivered l-DOPA gel likely penetrates the brain via the trigeminal and olfactory nerves that connect to other brain regions. — The Health
Dr Wael MY Mohamed is with the Department of Basic Medical Science, Kulliyyah of Medicine, International Islamic University Malaysia (IIUM).