Current Research to Slow or Stop Parkinson


A recent webinar summarized on-going efforts to halt Parkinson disease, including several phase III trials.

A recent Michael J. Fox Foundation (MJFF) webinar convened on October 15, 2015, titled “Studies to Slow or Stop Parkinson’s Disease.” Panelists included Dave Iverson, Contributing Editor of MJFF; Bill Shepherd, MJFF council member and a person with Parkinson disease (PD); Lorraine V. Kalia, MD, PhD, a neurologist and assistant professor at Toronto Western Hospital/University of Toronto; and Todd Sherer, PhD, CEO of MJFF.

The panel summarized current efforts to halt PD, which focus on clearing out the protein alpha-synuclein, identifying compounds that lower PD risk and progression, as well as finding therapies that can prevent brain cell loss in PD. Many therapies that may be able to stop or slow down PD are currently being tested.

Dr. Kalia noted several factors that in epidemiological studies are associated with decreased PD risk, including nicotine, blood urate, and certain blood pressure medications. She cautioned that associations do not necessarily imply causality, but can help direct where future research should focus.

Dr. Sherer discussed innate immune system approaches that may help to combat alpha-synuclein accumulation in PD based on some early research studies. The companies Biogen and Prothena currently investigate the use of alpha-synuclein antibodies for PD. A third company, AFFiRiS, studies a fake version of alpha-synuclein in a vaccine-like approach. All of these approaches have reached stages of human clinical testing.

Isradipine, a calcium channel blocker already used to treat hypertension, may also be neuroprotective in PD. The drug is currently in phase III trials (known as STEADY-PD) to determine if it can be used to treat early PD. The University of Rochester Medical Center and Northwestern University are co-leading the study of this treatment. Bill Shepard described his own participation in the phase I stage of trials of this medication. He decided to be a part of the trial since the medication is already approved and therefore would not be a risky treatment.

Shepard also emphasized that in order for clinical research to move forward the PD community needs to actively participate in clinical trials. He noted that the risks are fully disclosed and the participants can often benefit from leading medical care and potentially the best treatments. “Just about everyone can participate in clinical trials and help drive the research forward” said Shepard.

Shepard has continued isradipine since completing the trial but noted that to eventually understand whether or not the drug is neuroprotective, the PD community needs to await the results of the phase III trial.

An antioxidant urate precursor, known as inosine, has been associated with lower risk of PD and slower PD progression. Ionsine in laboratory assays appears to be neuroprotective. The Safety of Urate Elevation in Parkinson’s Disease (SURE-PD) is a current clinical trial in phase III. The study examines the effects of inosine on PD and results from the phase III trial are still pending.

Nicotine is often viewed in a negative light, but interestingly, PD is less common among smokers when compared to non-smokers. Doctors would, of course, not recommend smoking to prevent PD. Nicotine in patch forms is being tested as a preventative for PD progression in the NIC-PD trial.

Neuroprotective factors are another avenue in PD research. These are protective molecules that prevent neuron death. Unfortunately, getting neuroprotective factors into the brain is challenging and trials of neurotrophic factor injections and gene therapies has been wrought with difficulties in getting the molecules to the right areas of the brain. Dr. Kalia also noted that it is possible to boost neurotrophic factors naturally through exercise, even if neurotrophic factor gene therapies and injections are ultimately not effective.

A gene therapy that delivers glial cell line-derived neurotrophic factor via an adenoviral vector is, however, currently in trials (AAV2-GDNF). The National Institutes of Health is conducting the study, which is in phase I in people with advanced PD.

The panel also discussed the need for PD biomarkers to monitor treatments in clinical trials, including biomarkers from brain imaging, blood, and cerebrospinal fluid.

For those interested in more details of what the panel discussed, the webinar has been recorded and can be viewed at the MJFF website.

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