"Parkinson's Hope: The Power of Stem Cell Therapy"

Kavya Vinayan Pushpalatha and Alphy John

A ray of hope shines for those battling Parkinson’s disease (PD)!

A clinical trial to assess the efficacy of stem cell therapy in treating PD (STEM-PD) is underway (Kirkeby et al., 2023). This state-of-the-art approach involves transplanting specialized cells derived from stem cells into the brains of patients, with an aim to replace damaged neurons. This trial would shed light on the therapy's safety and potential to reduce Parkinson's symptoms.

Graphical representation of stem cell therapy strategy for PD. Image acquired from Kirkeby et al., 2023.

Researchers at Lund University carry out this pioneering stem cell-based therapy which represents a significant advancement in finding a potential treatment for PD. This research will be pivotal not only in providing valuable preclinical data for STEM-PD therapy but also be key in design a clinical trial program that has received regulatory approval under the EU Advanced Therapeutic Medicinal Product (ATMP) regulation. If successful, STEM-PD holds the promise of offering a standardized and widely accessible therapy for patients with moderate PD, addressing the limitations of current treatment options.

What is Parkinson’s disease (PD)? 

PD is a neurological condition whose symptoms include challenges in movement, mental health, sleep, pain, and various other health concerns. PD poses an enormous burden to the health systems. Last 25 years have seen a doubling of the PD incidence. A census from 2019 showed that there are more than 8.5 million individuals diagnosed with PD (source: WHO). PD also caused 329,000 deaths in 2019, a 100% rise from 2000.

Image courtesy: https://www.verywellhealth.com/parkinsonism-causes-symptoms-and-treatment-5189631

PD is caused due to the degeneration of dopaminergic (DAergic) neurons in the substantia nigra region of the brain. The lack of these neurons leads to a decline in the vital neurotransmitter in the brain, dopamine (DA). DA is key in regulating body movements, and a reduction in its quantity is responsible for the manifestation of various symptoms associated with PD. The specific reasons for the loss of nerve cells remain uncertain. Most experts propose that a combination of genetic and environmental factors contributes to this process.

The symptoms of PD are classified depending on whether they are associated with motor or non-motor dysfunction. Motor symptoms include tremors, slow movements, and stiffened muscles. Non-motor symptoms include depression, anxiety, loss of balance, memory loss, loss of smell, and insomnia. The symptoms of PD progressively worsen over time, significantly diminishing overall well-being and quality of life.

Treatments so far…

The current treatments focus on reducing motor symptoms using drugs like Levodopa (L-DOPA) or dopamine mimics. Unfortunately, continuous oral administration of these medications over time reduce their effectiveness and can cause adverse effects, including neuropsychiatric complications and L-DOPA-induced dyskinesias.

How different is the new treatment strategy?

The fundamental idea of this novel stem cell-based therapy is to implant dopaminergic (DAergic) neurons in appropriate locations in the patient brain. This is to facilitate a more natural and targeted release of DA, in hope of restoring motor function without adverse effects of long-term oral medications. Researchers aim is to develop a standardized and scalable DAergic cell replacement product derived from pluripotent stem cells. Preclinical studies in mice models of PD have demonstrated that human embryonic stem cell (hESC)-derived DA neurons can effectively revert motor impairment symptoms.

Reprogramming somatic cell to induced pluripotent stem cells (hiPSCs) and differentiating them to cell-of-interest. Image acquired from Simmnacher et al., 2020.

Further reading..

Kirkeby, A., Nelander, J., Hoban, D. B., Rogelius, N., Bjartmarz, H., Novo Nordisk Cell Therapy, R., Storm, P., Fiorenzano, A., Adler, A. F., Vale, S., Mudannayake, J., Zhang, Y., Cardoso, T., Mattsson, B., Landau, A. M., Glud, A. N., Sorensen, J. C., Lillethorup, T. P., Lowdell, M., . . . Parmar, M. (2023). Preclinical quality, safety, and efficacy of a human embryonic stem cell-derived product for the treatment of Parkinson's disease, STEM-PD. Cell Stem Cell, 30(10), 1299-1314 e1299. https://doi.org/10.1016/j.stem.2023.08.014