Parkinson’s disease (PD) presents as problematic when developing effective treatments. In discovering that dopamine was deficient in post-mortem brains of PD patients, one would naturally surmise that replacing the dopamine would return these patients to normal. In fact, preserving, protecting, replacing, simulating, or preventing the loss of dopamine describes the state of play since the 1960s; helpful at first, but not in the long run. The severe side effects produced by these drugs, in the presence of reduced therapeutic benefit over time, results in a condition where “…the treatment becomes worse than the disease itself.” With overdosing, polypharmacy, and severe side effects serving as the main shortcomings of pharmacological intervention, patients are increasingly deprived of quality of life as the disease advances.
It wasn’t until 1996 that we began thinking laterally, by asking whether the secondary symptoms of the disease might be improved by less invasive means: perhaps by tapping into the function of another system separate to those described in traditional theories of dopamine transmission. And this is precisely what is now happening. Three key papers appeared in the biomedical press between 1996 and 2007 employing bright light therapy (BLT) to improve the depression and insomnia that are comorbid with PD. With compromised circadian function being the underlying rationale, an open label trial, a case series study, and a randomized controlled trial demonstrated that not only did the non-motor and motor symptoms improve, but the drug dosage required to regain symptomatic control could be significantly lessened. Further confirmation of this effect has been found in both open label and controlled trails (1, 2, 3, 4, 5), with increasing focus on how the circadian system might be involved.
Importantly, BLT is the vanguard demonstrating that CNS systems, other than the midbrain dopamine system, are involved in the aetiology, progression and treatment of PD. This is the case, not because the circadian system is propelled by dopamine per se, but more likely because it involves keeping dopamine and the pineal hormone melatonin in balance within the context of circadian function.
When exploring various means of repairing or altering compromised circadian function in PD, many mechanisms have been defined and tested pre-clinically, but none has yet proven to be as clinically effective as BLT. Furthermore, when compared to other, more general approaches, such as cell replacement or antioxidative strategies, BLT has had a more notable record of clinical success.
Whereas the clinical benefits of BLT are currently focused on improving the non-motor symptoms of insomnia and depression, many studies have shown that therapeutic benefit can extend across motor and non-motor symptoms alike. A recent study showed that BLT alters peripheral clock gene expression as it exerts its therapeutic effect. The biomedical community is now challenged to refine BLT as a minimally invasive, anti-Parkinsonian therapy. For the first time since the role of dopamine was defined in the aetiology of PD, we now have compelling evidence that the circadian system, as a separate anatomical entity, can be effectively modified by BLT to improve the quality of life in this debilitating disorder.
Gregory L. Willis PhD is Director of the Bronowski Clinic and the Bronowski Institute of Behavioural Neuroscience in Melbourne. He has been the pioneer of animal and clinical studies of the mechanisms and efficacy of light therapy in Parkinson’s disease.