What Types of Stem Cells Are Used for Treating Parkinson’s Disease?

It is discomforting to imagine waking up one day and finding it harder to move. Maybe your hands tremble slightly, or your steps feel stiff. These could be early signs of Parkinson’s disease, a condition that affects millions worldwide. But what if the answer to unlocking its mysteries wasn’t just in medication, but within our very genes? Delve into this article to explore the fascinating link between genetics and Parkinson’s disease. We’ll uncover how our DNA plays a role, the latest research on potential treatments, and why the future for managing this condition might be brighter than ever.

Exploring the Genetics Behind Parkinson’s

While the exact cause remains unknown, genetics is believed to play a crucial role. It is evident from the discovery of genes that have been associated with the disease and known genetic factors that increase the risk of PD. We have been able to explore the cause of PD through:

• Family Studies: These studies identify genes for forms of PD that are passed down through generations. By studying families with members sharing the same genetic mutation scientists can pinpoint the gene linked to the disease. The study also helps in identifying a larger number of genes than just looking at a few of these studies.
• Research on Associations: In this type of study, researchers look for genes that if mutated (become faulty), may increase the risk of developing PD. This method is more common, as identifying and testing disease causing mutations often leads to a profound impact on the disease. It involves analyzing groups of patients and controls due to the influence of these genetic variants.
• Genome Wide Association Studies (GWAS): This method scans the genome, without bias to identify potential risk factors.

Understanding Parkinson’s Genetic Makeup

There is evidence pointing to genetics playing a role in the risk of Parkinson’s disease. However, the genes responsible for causing the disease show a range of variations. Through family and association studies, researchers have discovered more than 20 genes that have been associated with forms of parkinsonism, which include:

• Gene Locations: EIF4G1, PARK13, PARK15 and PARK1.
• Risk factors: HLA, GAK, MAPT, BST1, PARK16 GBA, LRRK2 and SNCA.

You might ask, “Can we screen ourselves if we are at risk of developing Parkinson’s disease?” We have tools available to test the risk of developing Parkinson’s, but it is not a regular testing method. The reason is that we can share the news that you are at risk of developing Parkinson’s, but whether it will affect your health or day-to-day life is uncertain.

Neurologists can confirm the diagnosis of Parkinson’s disease in India through a neurological exam and DaTSCAN. With this exam, doctors can share with you if the dopamine levels, linked to Parkinson’s disease, in your brain are low or normal.

There are a few genetic factors that increase the

• Autosomal recessive: Changes in genes like PARK6, PARK7, and PARK2 usually result in the onset of the disease displaying symptoms such as tremors and stiffness without accompanying features and occasional non motor symptoms. Both gene copies in the individual from each parent need to be mutated for the disease to appear. The resulting symptoms are those of a pure parkinsonian disorder.
• Autosomal dominant: One copy of the genes like PARK1, PARK4, and LRRK2 inherited from a single parent is adequate for developing the disease. A fault (mutation) in these genes results in late-onset of PD, with minimal to no symptoms detected early on. The disease also progresses slowly when compared to other forms of PD.
• X-chromosome linked: This type of PD is most commonly seen in males that carry mutations (fault) in the TAF1 gene of the X chromosome. The symptoms of the condition usually occur early in adulthood starting with cramps in the muscles near the head region that later spreads to the whole body. The progression of the disease is slow in mild cases and fast in severe cases.

The specific traits caused by these genes vary greatly ranging from parkinsonism resembling PD (the common form) to early onset parkinsonism with either just motor symptoms or a combination of both motor and non motor features.

As we delve deeper into research, it is likely that we will discover genes and enhance our comprehension of how genetic differences intertwine with elements to impact the onset of diseases.

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Parkinson Treatment in India

We have a long list of genetic factors, but we do not know what the exact cause of PD is. Recent studies have indicated a connection between autophagy, a cellular recycling process, and the progression of diseases. They found that there are disruptions in autophagy within the brains of individuals with PD and in animal models. This suggests that enhancing autophagy could serve as a treatment approach for PD.

Stem cells and PD

For a solution, researchers turned to mesenchymal stem cells (MSCs). These cells possess the ability to transform (differentiate) into specialized cells. They have displayed the potential to enhance the removal of alpha synuclein, a protein linked to PD, and manage autophagy activity in PD models. MSCs are able to achieve this by triggering the autophagy signaling. Moreover, their secretome (released factors) contains substances that can stimulate genes associated with autophagy, potentially aiding in getting rid of waste.

The MSC secretome has been demonstrated to activate the PI3K/Akt pathway, which is involved in functions like nutrient absorption, growth, metabolism, and cell proliferation. This activation of the pathway could contribute to the effects on nerves and neurons because of MSCs.

Neuroinflammation is a recognized aspect of PD. Studies have shown that MSCs can modulate inflammation levels and support tissue repair processes, positioning them as a viable option. We can even call them the “sensor and switcher” of the immune system because they regulate its response. It is possible for MSCs to shift microglia (immune cells in the brain) activity from inflammatory to anti-inflammatory through a signaling pathway, known as CX3CL1/CX3CR1 thus enhancing neuroprotection. They also produce factors such as GDNF, NGF, and BDNF, that prevent the death of dopamine neurons and boost neurogenesis.

MSCs also release substances such as VEGF and FGF2, which have the ability to enhance the formation of blood vessels and encourage cell multiplication, possibly aiding in the restoration of tissue.

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Stem Cell Derived Exosomes for PD

Exosomes derived from mesenchymal stem cells (MSCs) and other sources have shown neuroprotective effects in PD models. Exosomes contain cargo reflecting their cellular origin. These exosomes may promote neuronal survival, reduce inflammation, and stimulate the growth of new blood vessels, critical for brain health. These exosomes have been shown to prevent up to 80% of dopamine neuron death in PD models.

Because exosomes possess the ability to cross the blood-brain barrier, they are also explored to see if they can be used to offload dopamine or enzymes involved in dopamine synthesis. This can potentially mitigate dopamine deficiency, a hallmark of PD. Stem cell exosomes offer a novel and promising approach for Parkinson’s treatment or gene therapy.

Conclusion

The current results of several studies substantiate how MSCs are safe to use and show short to long term improvements in PD individuals with no side effects. This proves how MSCs have a multifaceted approach to potentially treating PD. At present, we can not cure the condition, but it holds significant importance in improving the lives of PD patients.