THE HEALTH | MAY-JUNE , 2022

BRAIN BITES

BY DR WAEL MY MOHAMED

Researchers are investigating whether scentprocessing 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

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 .”

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 levodopaloaded 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 bloodbrain 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 ).