The IMF said in its latest staff report that after decades of increasing global economic integration, the world is facing the risk of fragmentation, which could reduce global economic output by up to 7 percent. And with the addition of technological "decoupling," the loss in output could reach 8 to 12 percent in some countries, it warned.
In addition to the COVID-19 pandemic, high inflation, geopolitical conflict, and regional economic uncertainty, among others, the IMF report actually points to one of the biggest worries for the global economy in 2023. At a time when the US push for the technological "decoupling" and abnormal transfer of industrial chains is "killing" globalization, it seems that fragmentation of the global supply chains and trade has become an inevitable trend, which is bound to seriously affect the global economic recovery.
The US is to blame for the current anti-globalization trend of the global economy. Over the years, the US has been trying to promote the returning of manufacturing jobs through various policies. During the process, these policies are gradually deviating from the principles and rules of free trade time and again as Washington increasingly doesn't care whether it hurts the interests of the rest of the world, such as requiring TSMC and South Korean chipmakers to shift production to the US.
For example, at the "relocation ceremony" of TSMC's first plant in Arizona last month, TSMC founder Morris Chang said that globalization and free trade are "almost dead," while US President Joe Biden claimed "American manufacturing is back" in his speech. This is perhaps the perfect manifestation of the US' disdain for globalization.
Against this backdrop, there is an increasing tendency that factors determining global industrial chains and resource allocation are politicized, deviating from economic considerations. Some countries have a strong desire to strengthen their domestic industries and become wary of international cooperation, which may be the biggest crisis to globalization.
By distorting and politicizing industrial policy, the US may be able to see a certain degree of manufacturing recovery in the short term, but in the long run, it will lead to a significant increase in the costs, creating unnecessary chaos in the global industrial chain.
Moreover, with the excuse of improving the so-called supply chain security and resilience, the US has been seeking to isolate China from global supply chains, which is another important reason for the growing trend of industrial fragmentation. In the semiconductor sector, for example, the US has been hamstringing China with export bans for years, and it announced in October escalated measures to cut China off from certain semiconductor chips made anywhere in the world with US equipment. The US is also reportedly in discussions with Japan, the Netherlands and South Korea over restricting semiconductor exports to China.
The move affects not only China, but also the global semiconductor industrial chain, shattering the traditional consensus on the global division of labor that has developed over the past few decades. Everyone is a loser in the US-led "decoupling" drive, including American companies. The third quarter of last year alone saw more than $1.5 trillion wiped from the combined market value of American-listed chip businesses, according to an Economist report.
Indeed, the US is pursuing its global strategy aimed at containing China not just in the semiconductor sector, but also in such industries as photovoltaic and electric cars. By adopting various legislations targeting China, it has tried to wean its economy off or reduce its reliance on Chinese supply chains, so as to undermine China's economic momentum.
Yet, China's industrial chain and supply chain is an inseparable part of the world, also an important driving force of the global economy. It is widely expected that China's economic recovery will become a major source of optimism for the global economy in 2023. Washington's attempt to construct a global supply chain that excludes China and to contain China's rise will cause disruption to this chain and will have a major impact on the global economy and globalization, which is obviously not in line with the interests of most countries in the world, including the US. Global economic recovery needs China's supply chain. There is no substitute. If the US continues on the path of industrial fragmentation, it will be the number one obstructer of the global economic recovery.
Ballooning US debt a ticking time bomb for world economy
Illustration: Chen Xia/Global Times
The US policymakers seem to have steered the world's largest economy into unchartered territory, as it now faces multipronged challenges including persistently elevated inflation running at a 40-year high, a sputtering economy dragged down by a technical recession in the second quarter this year, and an enlarging federal debt which exceeded $31 trillion as of October 4 - a ticking time bomb for America and the world as well.
For the first time in history, the US' public debt outstanding has surpassed $31 trillion, data from the country's Treasury Department showed. A trillion dollars of debt was added in the past eight months alone, and it is close to reaching the $31.4 trillion debt ceiling that the US Congress set for the Biden administration's borrowing until early 2023.
Since Barack Obama took office in January 2009, the US' aggregate borrowings have kept galloping, with the current reading of $31 trillion nearly tripling $10.6 trillion worth of debt in early 2009. When Donald Trump came to the White House in early 2017, he inherited $19.9 trillion debt. And, when Biden took office in January 2021, the federal debt was $27.8 trillion. It is widely expected that the US national debt will hit a minimum of $50 trillion by 2030, according to estimations by some American institutions.
Like Japan, the US is increasingly becoming a heavily-indebted economy, with its national debt now accounting for approximately 140 percent of last year's GDP. Whether the US is going to face "two lost decades" of Japan-style anemic economic growth is unknown yet, but an incessantly bulging federal debt will definitely pose more problems for American policymakers, while chipping away at the US dollar's global reserve currency status, because a foundering US economy will inevitably reduce the importance of the greenback.
To make things worse, with inflation still running at more than 8 percent, the Federal Reserve has vowed to continue to raise interest rates in the coming months to tame stubborn price rises. Higher interest rates means that the US government will have to pay more for its huge borrowings, which raises questions about Washington's ability to service its debts, including the principal and increasingly larger interests.
As interest rates on US Treasury bonds rise, so will the federal government's borrowing costs. The US was able to borrow cheaply to respond to the COVID-19 pandemic because interest rates were at historically low in 2020. Now, interest rates on 20-year US Treasury bonds have grown to around 4 percent, meaning the US government will have to pay added interest costs of about $100 billion this year as the US central bank has raised rates from zero to 3-3.25 percent now. In May, the Congressional Budget Office (CBO) projected the US' annual interest costs will reach $399 billion this year, which is forecast to surge to $1.2 trillion in 2032.
The long-haul fiscal challenges facing the US are mounting. Since the 2008-09 global financial crisis, the US government has relied on quantitative easing (QE) monetary policy, through heavy borrowing from home and abroad, to maintain a relatively fast economic growth, in addition to maintain lavish spending on its military, medical care and other social welfare projects. However, the structural imbalance between spending and revenues that existed before the pandemic has been intensifying, causing American federal debt levels rapidly piling up.
If the US national debt exceeds $50 trillion, while its GDP struggles at around $25 trillion, then the world's largest economy will be truly thrust into a big trouble. US GDP this year is estimated to be flat against last year's figure. It may recede in 2023 and 2024, as the Fed's higher rates chip in, while Trump's tariffs war plus Biden's semiconductors tussle with China will further dim the US' economic prospects.
And, there will be fiercer and also uglier partisan fighting in Washington on congressional appropriations in the coming months, because the federal government will be constrained by the lawmakers and American public to borrow more to fund defense, infrastructure, education, medical care, elderly's pensions and other initiatives. For many years, US presidents, both Republican and Democratic parties, have avoided making hard choices about the budget, failing to put it on a sustainable path.
With a ballooning national debt and a struggling economy, the US policymakers will get to find that the global reserve currency of the dollar is set to erode, as the country's growing budget deficits will naturally raise concerns about the ability of Washington to pay back the debt. If the US government continues to sell more Treasury bonds or even parachuting printed money to American households and enterprises, investors will take caution and avoid buying the bonds. In the past several years, more central banks have begun to reduce their holdings of US dollar-denominated assets.
Once their faith in buying the US Treasury bonds is undermined, or if the US government further bundles its policies to cause a fiscal default one day, more foreign countries will join the rush to de-dollarize by dumping the US assets.
Is the Biden administration able to stop the US national debt from swelling? The chances are very slim. In 2021 and 2022, the US debt has expanded by more than $3.2 trillion under Biden's watch. The debt count is expected to surge to $35 trillion when Biden completes his current term in January 2025. So, the country's fiscal sustainability will draw more close scrutiny by investors both domestically and around the world.
Hu Says: China opened its border on Sun, and the dynamic zero-COVID policy which protected the Chinese people for three years has passed into history. China will return to the world as an engine of global economic growth with new economic and political influence.
Despite the difficulties and challenges ahead, we are always
inspired by this spiritual power. Such a national spirit has been fully
manifested in the Spring Festival Gala.
The year of the Rabbit would be a stabilising period that could see Malaysia’s gross domestic product (GDP) growth moderate from the expected 8.4% for 2022 to 4% in 2023, although the latter figure may still be considered a “robust” expansion rate, according to HSBC’s Global Research Economics team.
The team said Malaysia has been a clear regional outperformer in a turbulent 2022, experiencing a GDP year-on-year (y-o-y) growth of 14.2% for the first nine months of last year, making it Asean’s top performer for the second consecutive quarter in the third quarter of 2022 (3Q22).
“Despite a cooling trade cycle, Malaysia’s external engine remained surprisingly resilient in the second half of 2022, benefitting from its well-diversified mix of exports.
“While some commodity prices cooled, they have stayed at an elevated level, boosting the country’s energy exports.
“Meanwhile, Malaysia’s electronics exports have defied the global trend, pushing its trade surplus to a historic high,” the team said at the HSBC 2023 Asian Outlook conference yesterday.
The team said Malaysia’s booming domestic demand has been the main growth driver, reflecting a continued reopening tailwind.
Underpinned by an ongoing improvement in its labour market, retail sales have seen speedy recovery, with consumption of goods and most services exceeding pre-pandemic levels, except for some tourism-related sectors, it said.
As such, its co-head of Asian economics research Frederic Neumann predicted that Bank Negara would have to raise interest rates in the second quarter of 2023 – most likely to 3.5% – to keep a lid on lingering upward price pressures spilling over from last year due to the country’s extraordinary economic resilience.
On top of that, Neumann said Malaysia would remain one of the key beneficiaries of the supply chain “rejigging” that is occurring across Asia.
He expects high amounts of foreign direct investments continuing to pour into the country that would lead to further expansions in its export capacity.
“China’s reopening will benefit Malaysia’s economy, just as it will for other neighbouring economies. This is because China is a major export partner for Malaysia, which means the commodity angle would be positive.
“More importantly, Chinese companies are also investing in the country, particularly in the manufacturing sector,” said Neumann, adding that bilateral travel would also benefit the tourism sector.
The HSBC global economics research team also pointed out that while the local inflation rate has remained largely under control, in fact the lowest in Asean thanks to generous governmental subsidies, it has nonetheless accelerated.
“In particular, core inflation recently overshot 4% y-o-y, reflecting booming local demand. A large part of the inflation trajectory in 2023 will depend on the new Budget (2023).
“All in all, we believe core inflation will likely remain sticky and high in the near term and, as such, we recently upgraded our average core inflation to 3% for both 2022 and 2023,” it said.
Meanwhile, HSBC head of equity strategy for Asia-Pacific, Herald van der Linde, is expecting the FBM KLCI to hit 1,570 points by the year-end, representing a slight upside to its current standing.
He said the rationale for the forecast is the local bourse’s “stable” characteristic.
“When markets are down, investors want to be in Malaysia because it does not recede as much as the other countries.
“Conversely, if markets go into a recovery mode, as we are expecting in 2023, Malaysia is not expected to catch up as much either. It is more steady than many other bourses in the region.”
On a separate note, the team is bullish about China, projecting it to stretch its GDP growth to 5.8% next year from the 5% forecast for this year.
Chief economist for Greater China Liu Jing expects a strong rebound in the Middle Kingdom from 2Q23, the same quarter she believes the country will fully re-emerge from the lockdown effects.
“We expect consumption, which has been a laggard so far, to come back to record a growth level of approximately 8% in 2023.
“When China emerges from pandemic, the impact of housing market policy support will also materialise, giving way to what should be a modest rebound in the housing sector this year,” she said.
Van der Linde said the environment for Asian equities in 2023 would be constructive and the team remains overweight on China and India, expecting them to be the fastest growing markets this year.
“We are selective on Asean and Thailand remains our favourite market,” he said.
On how the team sees the US Federal Reserve (Fed) behaving this year – which has been and will continue to be the other major factor influencing market movement aside from the reopening of China – Neumann sees the Fed to be holding on to its rate of around 5%, before pivoting by the middle of 2024.
The blood vessels that vascularize the central nervous system exhibit
unique properties which control the flow of cells, ions, and molecules from plasma to the brain. Referred to as the blood-brain barrier, it is vital for the protection of the brain and maintains homeostasis. Dysfunction of the blood-brain barrier is linked with a range of neurological conditions.
Blood is carried from the heart to organs and tissue throughout the body via systems of blood vessels. Vessels deliver nutrients and oxygen, whilst removing waste products and carbon dioxide and regulating how the immune system interacts with each tissue. This vascular system includes arteries, venules and veins and capillaries. Capillaries comprise the smallest segments of the vascular system, known as the microvasculature and have varying properties depending on the requirements of the area they vascularize.
There are three structural classes of capillaries: discontinuous, continuous fenestrated, and continuous non-fenestrated.
Discontinuous capillaries are found only in the liver and have intercellular gaps which allow for large molecules and cells to be transported between the blood and tissue, supporting metabolism.
Continuous fenestrated capillaries have small perforations in their cell walls which allows for molecular exchange. This is important in the areas that require frequent exchanges between blood and tissue, such as the filtration of waste products by the kidneys, or absorption of nutrients by the small ntestine.
Continuous non-fenestrated capillaries have a complete plasma membrane with no perforations, allowing only small molecules to pass between their intercellular clefts, such as water or ions.
The microvasculature of the central nervous system
The blood-brain barrier (BBB) is a term used to describe the unique properties of the microvasculature of the central nervous system (CNS). Blood vessels of the CNS are continuous non-fenestrated vessels but have additional distinct properties which tightly govern the movement of small molecules and ions. The BBB is highly selective, allowing only certain substances to travel from the bloodstream to the brain, providing the CNS with protection from pathogens, toxins, and neurochemical imbalance.
Cells of the blood-brain barrier
The interior surface of blood vessels is lined with endothelial cells, which form a one-cell thick layer referred to as the endothelium. Throughout other areas of the body, the endothelium is fenestrated. The endothelial cells of the blood-brain barrier however are securely fused together by tight cell junctions, a class of cellular structure that provides adhesion between neighboring cells, restricting diffusion of solutes between the blood and the brain.
Astrocytes, a type of glial cell
in the CNS, perform specialized functions called astrocytic end-feet, a projection from the cell body of the astrocyte to the membrane surrounding the endothelium. Astrocytic end-feet are thought to play a critical role in the formation and regulation of the BBB by interacting with endothelial cells and influencing the signaling to tight cell junctions.
Although primarily to maintain the BBB, astrocytic end-feet may also influence the transient opening of the BBB under certain physiological circumstances. Examples may include the passage of antibodies or cytokines that stimulate cell growth from plasma to the brain.
Blood Brain Barrier, Animation
Drug Transport Across the Blood Brain Barrier with Dr. Sadhana Jackson
Dysfunction of the blood-brain barrier
Functional imaging techniques such as functional Magnetic Resonance Imaging (fMRI) and Positron Emission Tomography (PET) and post-mortem analysis of brain samples have identified pathological dysfunction of the blood-brain barrier in many neurological disorders.
Although BBB pathology is typically a functional symptom of a primary neurological disorder, in some diseases including Alzheimer's Disease and Muscular Sclerosis, it has been hypothesized as a cause.
Multiple sclerosis (MS)
Multiple sclerosis is an autoimmune disorder whereby inflammation of the brain and spinal cord disrupts nerve signaling between the brain and body. Although the etiology of MS is unclear and likely to include multiple epigenetic factors, the breakdown of the blood-brain barrier is observed in the early stages of the disease. Recent research suggests that in MS, an abnormal immune response damages the myelin (the protein and lipid-rich substance surrounding cell axons) of the CNS. Myelin-producing cells, known as oligodendrocyte precursor cells (OPCs), however, are unable to cross the BBB to repair areas of damage. Thus,the BBB plays a role in both the initiation and maintenance of the inflammatory disorder.
Hypoxia and cerebral ischemia
Among the different stressors which induce disruption to the blood-brain barrier, hypoxic and ischemic challenges (reduced oxygen and/or reduced glucose delivery to the brain) are acutely injurious to brain function and can trigger the death of neuronal cells within minutes. Cerebral ischemia (stroke) induces severe brain injury and substantive disruption to the BBB.
Although the mechanisms by which hypoxia and ischemia disrupt the BBB remain unclear, oxidative stress is thought to be contributory. Oxidative stress is an imbalance of pro and anti-oxidants resulting in elevated reactive oxygen species (ROS) and may affect the integrity of the endothelium, breaking down the BBB.
Alzheimer’s Disease (AD)
Dysfunction of the blood-brain barrier has been well documented in post-mortem studies of individuals with established AD. However, recent studies which have imaged the brains of people with mild cognitive impairment (MCI) and early Alzheimer’s disease have shown the breakdown of the BBB prior to brain atrophy or dementia, suggesting it occurs at an early stage of the disease. Although the extent of BBB dysfunction and its causal role in Alzheimer’s disease continues to be debated, one theory suggests that BBB leakage caused by aging, illness, or injury could cause an inflammatory response leading to Alzheimer’s disease
pathology.
References
Abbott, N., Rönnbäck, L. & Hansson, E. Astrocyte–endothelial interactions at the blood–brain
Al Ahmad, A., Gassmann, M., & Ogunshola, O. O. (2012).
Involvement of oxidative stress in hypoxia-induced blood-brain barrier
breakdown. Microvascular research, 84(2), 222–225. https://doi.org/10.1016/j.mvr.2012.05.008
Caterina P. Profaci, Roeben N. Munji, Robert S. Pulido, Richard
Daneman; The blood–brain barrier in health and disease: Important
unanswered questions. J Exp Med 6 April 2020; 217 (4): e20190062. doi: https://doi.org/10.1084/jem.20190062
Daneman R. (2012). The blood-brain barrier in health and disease. Annals of neurology, 72(5), 648–672. https://doi.org/10.1002/ana.23648
Griffin, C. T., & Gao, S. (2017). Building discontinuous liver sinusoidal vessels. The Journal of clinical investigation, 127(3), 790–792. https://doi.org/10.1172/JCI92823
While this barrier functions to keep harmful organisms and substances out of our brain, it can also prevent useful drugs from crossing over.
WHAT is the most complex organ in the human body?
Undoubtedly, most of us will think of the brain.
Powered by energy-rich glucose and oxygen through the blood circulatory system, the brain is one of the biggest and most complex organs in our body.
This amazing organ, physically soft with a spongy mixture of protein and fat, weighs only approximately 2% of our total body weight, but utilises about a fifth of our energy!
The brain is composed of more than a hundred billion brain cells, which are made up of neurons and glia that communicate in trillions of connections known as synapses.
These unique neurons are nerve cells that conduct electrical impulses.
Meanwhile, glia cells provide structural protection and nutritional support for the neurons.
The brain is particularly vulnerable to toxic exposure and hypoxic conditions (i.e. low levels of oxygen).
Hence, the brain is shielded from an influx of harmful substances by a layer of tight-packed specialised endothelial cells known as the blood-brain barrier.
This barrier provides a natural protective function to impede the entry of harmful substances from the peripheral blood circulation into the central nervous system (CNS).
It is composed of different cell types, such as astrocytes, pericytes, endothelial cells, neurons and microglial cells.
All these cells play important and interconnecting roles in regulating the function of the brain.
The passage of molecules or ions through the blood-brain barrier is tightly regulated by cellular transporters and carriers.
This allows the delivery of nutrients into the brain, removal of unwanted toxins, and recruitment of leukocytes (white blood cells) or other immune system molecules necessary to maintain normal brain homeostasis.
The integrity of the barrier can be altered by the onset of disease.
Neuroinflammation in an ischaemic stroke (where there’s blockage of a blood vessel supplying the brain), systemic infection and inflammation, inflammatory bowel disease,and hypertensive encephalopathy are some examples of causes linked to a breakdown of the blood-brain barrier.
It is also a natural phenomenon correlated with ageing, initially occurring at the hippocampus situated at the medial temporal lobe, which is essential for episodic and spatial memory.
A link to three conditions
Epilepsy is a chronic CNS disorder characterised by recurrent seizures.
According to a study conducted by local researchers, the frequency of epilepsy was found to be higher in males.
Meanwhile, lifetime frequency, i.e. the frequency of epilepsy at any point of life in the population concerned (in this case, Malaysia) was estimated at 7.8 per 1,000 persons.
One in five patients with epilepsy in Malaysia died from the condition.
This implies the importance of treatments and access to adequate and appropriate treatment and care.
Super small and customisable
The various types of transport methods across the blood-brain barrier. — armin Kübelbeck/wikimedia Commons
There is also a growing body of evidence supporting the theory that seizures can promote amyloid-beta peptide and tau protein deposits, which can then lead to neurodegenerative processes that result in conditions like Alzheimer’s and Parkinson’s.
In two separate studies, it was reported that Alzheimer’s disease occurs six times more often in patients with epilepsy, and that seizures are highly repetitive and also occur in patients with dementia from Alzheimer’s.
A study done in the United Kingdom found that “people with epilepsy are 2.5 times more likely to be diagnosed with Parkinson’s disease than the general population”.
Nanoparticles for transport
An avalanche of research has centred on less or non-invasive methods to avoid some of the side effects associated with intrathecal administration of treatments into the spinal cord.
An intrathecal injection is where the drug is injected into the spinal cord fluid via a lumbar puncture.
Some of the side effects of this procedure include bleeding in the brain (haemorrhage), infection and and swelling of the brain (oedema).
In particular, there has been a growing interest in the use of nanoparticles to traverse through the blood-brain barrier, owing to their very small size, i.e. about 100 times smaller than a strand of human hair in diameter.
Nanoparticles can be designed with different shapes and sizes (within the nanometre range), as well as with desired properties (e.g. biodegradability) to meet the current demands in the production of functional materials.
They have widespread applications; however, the most commonly-known uses are in the cosmetics, food manufacturing and biomedical industries.
In 1995, cancer drug doxorubicin was the firstever nano-based product to be granted approval by the US Food and Drug Administration (FDA).
The number of nanotechnology products entering clinical trials since then have only grown larger.
As one of the approaches widely studied to facilitate the transport of medicinal compounds across the blood-brain barrier, the use of nanoparticles is especially promising as its mechanism does not affect the baseline permeability of the barrier.
Another fascinating approach involves the engineering of the protein corona, red blood cells and extracellular vesicles as nanoparticles bearing naturally-occurring components to cross the blood-brain barrier.
Nanoparticles made with this strategy have “stealth-like” properties as they can evade recognition and sequestration (and removal) by the immune system.
Importantly, this allows the nanoparticles to escape destruction in the event of an inflammatory response.
Crossing the barrier
In the case of epilepsy, Alzheimer’s disease and Parkinson’s disease, encouraging findings have been obtained with a host of nanoparticle strategies, especially with the versatility to accommodate more than one function into the nanoparticle design.
Nanoparticles have been engineered to effectively transport drugs across the blood-brain barrier by targeting receptors involved in endocytosis.
Endocytosis is a process by which a cell brings substances into itself.
The external substance is surrounded by a part of the cell’s membrane, which then breaks off to form a sphere with the substance within it, known as a vacuole.
For this process to occur, the external substance and cell membrane need to be able to “lock” onto one another.
One common way this occurs is when the substance has a ligand that matches with a receptor on the cell membrane, similar to a key and lock.
When the ligand (a molecule or atom) combines with the receptor (a protein molecule), its shape will be changed and this will trigger the endocytic process.
For this approach, the surfaces of the nanoparticles are modified with the appropriate ligands.
A wide range of ligands have been explored by researchers.
Examples include lectin, cardiolipin and heparin surface-decorated nanoparticles for Parkinson’s disease, and lactoferrin, apolipoprotein-e, transferrin and thiolated OX26 for epilepsy, Alzheimer’s disease, as well as Parkinson’s.
Research has also shown that adding in a scaffold of bispecific antibodies, i.e. anti-transferrin receptor and anti-beta secretase, reduces amyloid-beta peptide deposits in the cerebrospinal fluid and brain tissues of cynomolgus monkeys that received the intravenous (IV) injections.
Delivering potential treatments
Nanoparticles might also have the potential to target key mechanisms that fundamentally contribute to the three neurological disorders.
For example, an animal study using rats, described the delivery of an anti-epileptic peptide, galanin, that is capable of inhibiting glutamate release in the hippocampus.
An increase in glutamate, a neurotransmitter, is associated with the onset of seizures. Other studies have targeted the alpha-synuclein protein, which plays a role in Parkinson’s disease. It is thought that there is a misfolding of this protein in people with Parkinson’s, causing the proteins to clump together to form Lewy Bodies.
These clumps are theorised to be toxic and spread the disease throughout the brain as they get passed from one neuron to the other. One animal study using mice, assessed the inhibition of alpha-synuclein fibrillisation and protection from the progressive loss of dopaminergic neurons.
The formation of fibrils by the alpha-synuclein protein contributes to its toxicity, while dopamine, a neurotransmitter, is low in Parkinson’s disease. In another approach, researchers have proven that alpha-synuclein can be prevented from activating in microglial cells via scavenger receptor Cd36-binding nanoparticles.
The CD36 receptor is a glycoprotein found in cells in the bloodbrain barrier, such as astrocytes and microglia.
Another strategy uses glial cell-derived neurotrophic factor (GDNF), which is a key protein in regulating the survival and differentiation of brain cells that produce dopamine.
In a rat model of Parkinson’s disease, lipid nanocarriers loaded with GDNF plasmids were combined with microbubbles for Mriguided focused ultrasound-mediated effects that led to a reduction in nerve cell death and helped alleviate behavioural changes due to the disease.
A plasmid is a small DNA molecule within a cell, which is separate from chromosomal DNA and can replicate by itself. Another method of delivery
using GDNF retrovirus-loaded microbubbles and focused ultrasound also proved successful in delivering the GDNF retrovirus into nerve cells.
Alternatively, the nose-to-brain route of administration (rather than the conventional IV infusion or injection) could be a way to improve the delivery of drug-loaded and/or targeted nanoparticles to specific regions of the brain.
Delivery via this route bypasses the blood-brain barrier and enables direct delivery to the brain along the olfactory and trigeminal nerves.
This strategy, however, requires the nanoparticles to have augmented properties, such as protecting the molecules within them from being destroyed or damaged in the nasal cavity, and getting through the nose’s mucosal barrier.
More to come
A plethora of research on nanoparticles for disease treatment can be expected in the forthcoming years.
This includes clinical trials that can evaluate the potential shortand long-term adverse effects that may be triggered by their administration and uptake in the human body.
Although the journey towards clinical translation (i.e. nanoparticles approved for brain targeting and treatment) may be arduous as it requires substantial time and effort, there remains a light at the end of the tunnel for novel and tailored therapies to be developed in the near future to treat neurological disorders and injuries of the nervous system, in what may be known as the ‘precision medicine’ approach.
By Dr Lee Tze Yan who is a senior lecturer for Molecular Medicine at the Perdana University School of Liberal Arts, Science and Technology. Loo Yan Shan is a PHD student in Nanomedicine at Universiti Putra Malaysia. For more information, email starhealth@thestar.com.my. The information provided is for educational and communication purposes only, and should not be considered as medical advice. The Star does not give any warranty on accuracy, completeness, functionality, usefulness or other assurances as to the content appearing in this article. The Star disclaims all responsibility for any losses, damage to property or personal injury suffered directly or indirectly from reliance on such information.
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