Parkinson's Disease Stem Cells: Intravenous Injection Shows More Clinical Efficacy Than Intrathecal Injection

One of the frequent questions patients ask is whether intrathecal injection is more effective than intravenous injection for Parkinson's disease treatment. While it is a theoretically attractive approach, there are no clinical results from human studies yet that prove intrathecal injection is superior to intravenous injection.

Intrathecal injection involves inserting a needle into the lower back, not directly puncturing spinal tissue, but rather injecting cells into the cerebrospinal fluid (CSF) space that surrounds the brain and spinal cord. This is similar to floating cells into the fluid pathway that leads to the brain.

Intrathecal injection offers three theoretical advantages. First, it can bypass the 'pulmonary first-pass effect' where a significant number of cells are trapped in the lungs during intravenous injection, because stem cells are large and do not easily pass through pulmonary capillaries. Second, it can bypass the 'blood-brain barrier (BBB)' that prevents substances from entering the brain. Intrathecal injection directly administers cells into the CSF, not blood, avoiding this barrier. Third, it is expected to act closer to the inflammatory environment of the brain, potentially enhancing therapeutic effects.

The advantages mentioned above are still theoretical or have only been confirmed in animal studies. Even if cells enter the cerebrospinal fluid, it cannot be assumed that they reach deep into the substantia nigra striatum, which is the core area of Parkinson's disease. Furthermore, due to differences in spinal length and posture between animals and humans, there are limitations in directly applying animal study results to humans.

In 2012, a study was conducted where 17 patients, including those with Parkinson's disease, received their own bone marrow cells via intrathecal injection. After approximately 10 months of observation, no significant improvement in motor function or daily living activities was noted. To date, no clinical evidence has confirmed that intrathecal administration is more effective than intravenous injection for Parkinson's disease treatment.

A Phase 1 study published in 2021 administered mesenchymal stem cells from a donor's bone marrow intravenously once to 20 patients with mild to moderate Parkinson's disease. In the patient group that received the highest dose, motor scores in the 'off' state improved by an average of 14.4 points after one year, and some inflammation-related markers also decreased. However, this study involved a small number of patients and lacked a placebo group, focusing on safety as an early-stage study, making it difficult to definitively conclude that the score improvement was solely due to the stem cells.

A randomized, placebo-controlled Phase 2 clinical trial published in 2025 compared a group of 45 patients with mild to moderate Parkinson's disease who received repeated intravenous injections of allogeneic bone marrow-derived mesenchymal stem cells with a group that received a placebo. As a result, the proportion of patients with significant improvement in motor scores was higher in the group that received cells three times compared to the placebo group, and it met the statistical criteria set by the researchers.

Considering only human studies, there is insufficient clear evidence that intrathecal injection is more effective than intravenous injection for Parkinson's disease. Rather than concluding that direct intrathecal administration is unequivocally better or that intravenous administration is ineffective, it is more accurate to understand this as a stage of confirming the positive potential observed with intravenous administration through larger-scale studies.

If considering intrathecal injection, several conditions are necessary. First, the diagnosis of Parkinson's disease must be accurate. Patients with mild to moderate disease who still respond to dopamine medication, rather than those with advanced disease, are more suitable. Additionally, the patient must be able to safely undergo lumbar puncture (intrathecal injection via the lower back). Careful evaluation is essential, as severe spinal deformity or spinal conditions can increase the risk of the procedure.

Although intrathecal injection has theoretical advantages over intravenous injection, such as bypassing the lungs and the blood-brain barrier to directly deliver cells to the brain, there is no evidence from human studies yet that it sufficiently reaches the substantia nigra or striatum to produce better clinical outcomes. Rather, current clinical research shows more positive results for intravenous injection. Therefore, stem cell intrathecal injection for Parkinson's disease is currently an investigational approach, not a standard treatment, and existing drug therapy and exercise therapy should not be discontinued. If considering stem cell treatment, it is advisable to approach it within the framework of formal research that allows for long-term follow-up. There is a significant difference between theoretical possibility and proven efficacy in humans.