Parkinson's disease, a common neurodegenerative ailment, affects roughly 1 % of the population aged 60 and up, and the number of cases is anticipated to quadruple by 2040, posing a significant worldwide health burden.
The disease predominantly affects dopaminergic neurons in the substantia nigra of the brain, resulting in a gradual reduction in dopamine synthesis. This neurotransmitter shortage causes distinctive motor symptoms such as tremors, bradykinesia, and postural instability.
Current treatments rely mostly on drugs such as levodopa to replace dopamine levels or mimic its function, providing short-term symptom relief but failing to slow disease progression. Deep brain stimulation, an invasive surgical procedure that affects cerebral activity, is not appropriate for all individuals.
Stem cells have emerged as a highly promising way to treating Parkinson's disease, with the ability to not only improve symptoms but also address the underlying cause by replacing destroyed dopaminergic neurons.
Embryonic stem cells (ES) and induced pluripotent stem cells (iPSCs) are especially intriguing due to their extraordinary capacity to differentiate into a variety of cell types, including dopaminergic neurons.
These stem cells can be coaxed to mature into functioning neurons that can integrate into existing brain circuitry, release dopamine, and restore normal synaptic communication via a carefully controlled differentiation process.
BlueRock Therapeutics has made substantial progress in this field with its lead candidate, bemdaneprocel (BRT - DA01), produced from pluripotent stem cells.
In preclinical and early-stage clinical investigations, BRT-DA01 displayed good tolerability and ability to integrate into host brain tissue, resulting in the restoration of dopamine-producing cells.
Encouraged by these findings, the company plans to move BRT-DA01 onto Phase III studies, providing promise for a more effective and long-lasting treatment for Parkinson's sufferers.
Aspen Neuroscience is another significant player in the field of Parkinson's disease stem cell therapy. Its strategy employs autologous iPSCs, which are reprogrammed from the patient's own cells, lowering the chance of immunological rejection.
Aspen's research focuses on differentiating autologous iPSCs into dopaminergic neurons and transplanting them into patients' brains to provide a tailored and safe therapy alternative. Its current clinical trials are constantly examined, and preliminary results show encouraging indicators of cell survival and potential functional improvement.
Despite the enormous potential of stem cell therapy for Parkinson's disease, many substantial obstacles must be addressed before they can become generally available.
One of the most significant challenges is the large-scale creation of high-quality, functioning dopaminergic neurons from stem cells while retaining cell quality and uniformity.
When it comes to iPSC proliferation, preserving pluripotency and genomic stability over time is critical. Pluripotency enables iPSCs to develop into any cell type in the body, whereas genomic stability ensures that detrimental mutations are not acquired during the growth process.
High-quality Laminin protein, a key component of the extracellular matrix, is critical in this regard. Laminin interacts with specific receptors on stem cell surfaces, triggering a series of intracellular signaling cascades required for the cells' self-renewal.
In standard culture techniques, feeder cells or complicated matrices are frequently used to promote the proliferation of iPSCs. However, these approaches might cause unpredictability in cell growth and differentiation, making it difficult to scale up the manufacturing process.
To overcome this, researchers are actively investigating specified, xeno-free growth medium and improved bioreactor systems containing high-quality Laminin protein.
These systems are designed to accurately manage environmental parameters like as food supply, oxygen tension, and shear stress, resulting in an ideal environment for the development of iPS cells.
Despite these advances, genetic changes can still occur during long-term cell culture, potentially leading to genomic instability.
Advanced gene-editing techniques such as CRISPR-Cas9 provide the possibility of correcting or preventing genetic mutations, but concerns about off-target effects, which may result in unintended genetic changes, and ethical concerns about modifying human genes remain significant barriers.
Another key challenge is to improve the quantity and efficiency of iPSC differentiation into brain cells. Current differentiation techniques are frequently complex, time-consuming, and yield relatively low numbers of functioning neurons.
The process of leading iPSCs to differentiate into dopaminergic neurons consists of several consecutive phases, each requiring precise control of different signaling pathways. Key factors that promote neuronal development include FGF8b (fibroblast growth factor 8b) and SHH (sonic hedgehog).
FGF8b promotes specific signaling pathways in the early phases of differentiation, directing iPSCs toward a neural lineage. SHH, on the other hand, is required for the further specification and maturation of dopaminergic neurons.
Researchers are continually improving these differentiation regimens, experimenting with new combinations of cytokines, growth hormones, and small compounds to improve process efficiency. In addition, 3D culture techniques have demonstrated significant potential for enhancing the differentiation of iPSCs into brain cells.
These systems can better simulate the in-vivo microenvironment, facilitating more efficient cell-cell and cell-matrix interactions, resulting in the creation of higher-quality and more differentiated brain cells.
Scaling these streamlined processes to industrial levels while maintaining stringent quality control is still a substantial difficulty. To ensure the safety and efficacy of stem cell-based Parkinson's disease therapeutics, the differentiation process must be consistent and reproducible across large scale production.
Fortunately, ACRO provides a comprehensive approach for developing iPSCs into neurons, giving hope for overcoming these barriers and making stem cell-based Parkinson's treatments more accessible.
Key offerings
Laminin 521(Cat. No. GMP-LA5H24) & Laminin 511(Cat. No. GMP-LA1H25)
These universal ECM reagents, which come in both PG and GMP grades, are required for consistent hPSC growth and neuron differentiation. Following passage 10 GMP grade Laminin 521 or Laminin 511 was shown to boost hPSC growth and stemness (about 99% OCT4+SOX2+SSEA4+).
They may also promote neural progenitor cell (NPC) differentiation (about 99% purity with PAX1+SOX2+Nestin+ expression after 7 days) and dopaminergic neuron production (about 95% purity with TH1+MAP2+ expression).
ACROBiosystems’ bulk GMP Laminin protein (>10mg) will cut your manufacturing costs by at least 30%-50%. The GMP Laminin protein has already seen widespread usage in the PSC banking and differentiation process.
Differentiation factors (Cat. No. GMP-FGBH16, SH7-H5116, BDF-H5219, GDF-H5118)
The world's first GMP grade FGF8b, along with Noggin, Shh, BDNF, and GDNF, has been shown to significantly enhance dopaminergic neuron development (about 95% purity with TH1+MAP2+). They also exhibit exceptional batch-to-batch uniformity and stability due to rigorous quality control tests.
As a globally known, regulation-compliant supplier, ACROBiosystems follows all international legal and regulatory standards to ensure seamless integration into your manufacturing processes.
ACROBiosystems also provides a full range of customizable services to match your individual needs, providing comprehensive support to overcome any problem in stem cell therapy and drive the success of your projects.
About ACROBiosystems
ACROBiosystems is a cornerstone enterprise of the pharmaceutical and biotechnology industries. Their mission is to help overcome challenges with innovative tools and solutions from discovery to the clinic. They supply life science tools designed to be used in discovery research and scalable to the clinical phase and beyond. By consistently adapting to new regulatory challenges and guidelines, ACROBiosystems delivers solutions, whether it comes through recombinant proteins, antibodies, assay kits, GMP-grade reagents, or custom services. ACROBiosystems empower scientists and engineers dedicated towards innovation to simplify and accelerate the development of new, better, and more affordable medicine.
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