April is Parkinson’s Awareness Month, a time intended to raise the visibility of a disease that effects an estimated five to ten million people world-wide and to share its personal, societal, and scientific impact.

The medical community has been “aware” of this disease since its published description by James Parkinson in 1817. Let that sink in! Physicians and scientists have spent at least the last two centuries trying to understand, treat and cure what was initially described as “paralysis agitans,” or shaking palsy. Are we finally getting closer to a durable treatment or potentially a cure?  

Parkinson’s disease, as we know it today, is a progressive, degenerative disorder of the brain characterized by a resting tremor, slowness of movement, limb rigidity, and problems with gait and balance, though symptoms can vary among individuals. The disease occurs primarily in the aged brain, although an estimated 4% are diagnosed before age 50.

The pathology underlying Parkinson’s is complex, but the critical defect appears to be the loss of a discrete population of neurons in the brain that produce dopamine, a chemical messenger released by neurons also known as a neurotransmitter, that is important in the coordination of movement. While these neurons comprise less than 0.001% of the estimated 85 billion neurons in the brain, their loss has a significant functional impact. Unfortunately, the underlying disease process that leads to the loss of these cells is not well known.

Because dopamine has such a critical role in Parkinson’s disease, researchers have sought to determine whether treatments that restore or replace this neurochemical in the brain can treat disease symptoms. Over the past four decades researchers have tried to treat Parkinson’s by replacing the lost neurons themselves, or the dopamine produced by this specific population of neurons.

 One approach that has had success is the use of L-Dopa, a chemical precursor to dopamine that upon entering the brain is converted into dopamine. This medication has provided relief to patients with Parkinson’s but it has limitations, including the potential for significant side effects such as abnormal heart rhythm, altered mental status, aggressive behavior, to name a few, and patients may develop resistance to the drug’s effects over time. These issues make the long-term use of L-Dopa unsustainable for most patients.

While advances in drug development are improving the use of L-Dopa, another approach to treat Parkinson’s is the replacement of dopamine-secreting neurons via cellular replacement therapy. The rationale behind this approach is that the defective cells can be replaced by healthy ones that, upon transplantation into the proper area, will form connections with existing cells and then secrete dopamine locally and restore normal movement.

While several cell types have been tested for their ability to treat Parkinson’s symptoms, clinical trials conducted in the 1980s using fetal neurons have provided proof-of-principle that this approach can work in humans. An analysis of patients 20 years after receiving this treatment suggested that cellular replacement therapy could provide durable relief of symptoms for some, though not all, patients. It should be noted that at the time of the trial a pure population of dopamine-producing neurons could not be obtained, so a variable mixture of immature fetal cells was used in the transplant. It’s not known whether a more defined population of cells might produce more robust and consistent relief.

As time advances, so usually does technology. The use of pluripotent stem cells  provides a more precise approach to generate a highly enriched population of dopamine-secreting neurons for replacement cell therapy. Pluripotent stem cells such as embryonic stem cells or induced pluripotent stem (iPS) cellscan be specialized in a laboratory to become dopamine-producing neurons in high numbers and at high purity. These pluripotent-derived dopaminergic neurons have proven effective at ameliorating symptoms in animal models of Parkinson’s disease, but they have not yet been tested in humans. The ultimate test of this approach and its effectiveness will be assessed in rigorous clinical trials conducted around the world.

In addition to developing potential cellular replacement therapies, stem cells also can be used to model Parkinson’s disease and better understand what’s causing the loss of these neurons, an insight that could lead to a cure. For example, human iPS cells derived from Parkinson’s patients and converted into neurons that produce dopamine can be used to identify and understand the role of specific genes in the development of Parkinson’s disease. This includes looking for mutations that lead to Parkinson’s-like effects to screening drugs that could be used to treat the disease.

The hope is that the advances in stem cells and cellular therapy, along with other approaches, have brought us to the doorstep of a durable treatment for Parkinson’s disease. Although curing Parkinson’s will require significant advances in our understanding of the disease and what triggers it, biomedical science is making strides in advancing treatments and improving patients’ lives.