Emerging Research and Future Treatment Directions

Because the exact cause of Parkinson’s disease (PD) remains unknown, and because there are not yet treatments to stop or delay the progression of the disease, research in PD is of critical importance. Research in PD covers many areas, including research to better understand and diagnose PD in its earliest stages, research on new therapeutic approaches to manage symptoms and slow the progression of the disease, and research into ways to prevent PD from developing.

Research can be broken down into three types:

• Basic research, which encompasses scientific discoveries in the laboratory
• Translational research, which focuses on tools and resources that speed the development of therapies into practice
• Clinical research, which develops and studies new therapeutic approaches to PD¹

Some of the research projects and areas of focus in current PD research are briefly summarized below.

Biomarkers for Parkinson’s disease

As a chronic, progressive disease, the ability to intervene and slow the progression is in the earliest stages of PD. Scientists are searching for biomarkers (biological signs of the disease) that are evident in the early stages of PD to be able to diagnose and treat the disease before symptoms worsen. Some of the biomarkers that researchers have identified as being predictive of PD include rapid eye movement (REM) sleep behavior disorder (abnormal behavior during REM sleep that causes the person to act out their dreams), reduced sense of smell, subtle motor dysfunction (such as decreased expression in the face or voice), constipation, urinary dysfunction, and sexual dysfunction. Researchers are also looking for biomarkers in urine, cerebrospinal fluid or blood that may help diagnose the disease, particularly in its early stages. Another intense area of research is finding compounds that allow imaging of the brain to diagnose PD and hopefully identify the condition in the early stages of the disease.²

Targeting alpha-synuclein

Alpha-synuclein is believed to play a significant role in the development of PD. The accumulations of alpha-synuclein into clumps in neurons (also called Lewy bodies) are a key characteristic of the disease and cause dysfunction in the nerve cells. Immunotherapy can either use the existing processes of the immune system to stop or treat a disease (active immunotherapy), or antibodies can be identified in the lab that can bind to alpha-synuclein and neutralize it.³

Another area of research is focused on compounds that prevent, stop, or reverse the clumping of the protein alpha-synuclein. Researchers hope that these modulators will slow or stop the progression of PD.³

LRRK2 kinase inhibitors

LRRK2 (leucine-rich repeat kinase 2) is a gene that has instructions that produce a protein. Mutations in the gene are associated with both hereditary and sporadic forms of PD. Mutations in LRRK2 are the most common cause of familial PD, accounting for 1% of all cases of PD. Research is underway to test several LRRK2 kinase inhibitors with the hope that these inhibitors can stop or slow the progression of PD.^3,4

Isradipine

Isradipine is a medication currently used to treat high blood pressure. It is being studied for its potential effect on slowing the progression of PD. While the exact mechanism of action is not fully understood, scientists believe that isradipine prevents the death of the neurons (nerve cells) that produce dopamine, the neurotransmitter (chemical messenger) that is responsible for producing smooth, purposeful movement. PD damages the dopamine-producing neurons which causes the motor symptoms of PD, such as stiffness, slowness of movement, and tremor.³

Induced pluripotent stem cells

Stem cells are cells that can become any different type of cell in the body. Scientists have discovered the ability to reprogram mature cells, such as cells from the skin of an adult, to an embryonic-like state, creating them into “induced pluripotent stem (IPS) cells.” These cells can then be programmed to turn into cells with properties very similar to dopamine neurons found in the brain. IPS cells provide two important potentials for research in PD: they could be used in cell replacement treatment and they can provide a cellular model.^3,5