Ongoing Observational Study
We have recently completed a large scale, long term, open label, photopharmacological study whereby patients have been treated for a period of time ranging from one to nine years. The results demonstrate that not only do Parkinson’s disease patients show a favourable, acute, therapeutic response to light in regard to their depression, insomnia and anxiety but also a progressive, incremental improvement in motor function is also seen over the longer course of the disease. This study is ongoing at the Bronowski Clinic, here in Australia, in the presence of a range of doses of dopamine replacement ranging from very high to subclinical. As an institution dedicated to the practice of translational neurobiology we endeavour to bring new, non-invasive therapies to the clinic as soon as is practicable to alleviate the suffering and return quality of life to Parkinson’s disease patients.
Double Blind Placebo Controlled Trials
Multi-centre double blind placebo controlled trials are in the planning stages as a collaborative project between The Bronowski Institute of Behavioural Neuroscience in Australia and academic Institutions in the U.S.A. From these trials we expect to refine our current treatment regimen using the photopharmacological approach by increasing its therapeutic benefits and further reducing the side effects of dopamine replacement. It is essential that our hypothesis is put to the test implementing double blind, placebo controlled strategy, as it remains the golden standard to test various therapeutic avenues in biomedical research. These trials will be conducted with the intention of seeking approval from the FDA and other regulatory bodies worldwide. The key issues to address in these studies also include the effect upon disease progression and mortality associated with the disease.
Photopharmacological approach to treating Parkinson’s Plus Syndromes
Due to the limited response of Parkinson’s Plus syndromes to traditional dopamine replacement therapy we have done preliminary work on the effect of phototherapy or photopharmacological; treatment on multiple systems atrophy (MSA), progressive supranuclear palsy (PSP) and Diffuse Lewy Body Disease (LBD). In the preliminary case studies to date we have observed that not only does the application of dopamine replacement in these patients produce unusually adverse effects but the strategic application of light effectively improves various motor, cognitive and vegetative symptoms of these disorders. The effect of prolonged phototherapy on PD symptoms and its mortality is also at the focus of work undertaken.
Photopharmacological Approach to treating various forms of tremor
In consideration of the effect that phototherapy has had on tremor in Parkinson’s disease we have tested the possible use of phototherapy on various forms of tremor. To date intentional tremor, familial, essential and benign tremor have had varying response to phototherapy, much of which has been favourable. Future observational studies will be undertaken to examine the potential benefit in patients with tremor but particularly in those dealing with issues of polypharmacy.
Intraocular Delivery of Therapeutic Drugs
Safety and Efficacy Trial
Now that the preclinical proof of concept work on the anti-Parkinsonian effect of intraocular administration of therapeutic drugs has been completed we are now moving toward Phase I Clinical trials to be conducted here in Australia. This will involve 6 Parkinson’s disease patients with the disease expressed bilaterally. This study will be undertaken with the intention of establishing the safety and efficacy of this method of drug administration. Ocular toxicology and confirmation of the safety of intravitreal administration of therapeutic candidates is currently underway.
Ongoing Preclinical Development
With numerous anti-Parkinsonian drugs now found to be effective when delivered by the intraocular route in models of the disease, further work on retinal involvement as a therapeutic option is underway. Completed preclinical studies on intraocular delivery of a catalogue of anti-Parkinsonian drugs and their relative therapeutic effects are being prepared for publication in international biomedical journals. Single injection or long term delivery systems are also being explored in regard to the intraocular route of therapeutic intervention.
Drug Addiction and Other Neuropsychiatric Disorders
There are many other benefits that are emerging from our work. Not only do our findings relate to the aetiology and treatment of Parkinson’s disease but as an extension of this, we have discovered that the retina and other parts of the circadian system might function, or malfunction, in disorders such as Schizophrenia and drug addiction. Furthermore, therapeutic intervention at the level of the retina might also provide a more effective way of finding minimal therapeutic doses as well as eliminating adverse side effects and optimising treatment compliance. Implementing less invasive means of treatment using phototherapy or phototherapy plus pharmacological intervention are also being explored as alternative approaches to established methods of treating these disorders.
During the course of our preclinical work, we found that the drug, which reversed experimental forms of Parkinson’s disease, also had a positive effect on models of other disorders. When symptoms of psychosis, anxiety and anorexia were measured at the same time, we found that our test drug, ML-23 (a melatonin receptor antagonist) and others like it produced significant improvement in experimental forms of these diseases. As with Parkinson’s disease, this work has provided a new direction and new hope for those suffering from these debilitating disorders.