When L-dopa made it big in Hollywood…

It has been almost 20 years since L-dopa hit the silver screen, making its debut in 1990 in the film Awakenings. Starring alongside this ingenious drug, were Hollywood actors Robin Williams and Robert de Niro. Awakenings tells the story of British neurologist Dr Oliver Sacks and his efforts to treat a group of catatonic patients at Beth Abraham Hospital, New York. The year was 1969 and L-dopa was beginning to make waves in the medical community.

Dr Sacks’ patients were survivors of the 1920s encephalitis lethargica outbreak, also known as sleeping sickness. Although they survived they were trapped in a state of torpor and deemed beyond recovery. After years of inactivity however, the impossible happened. The patients were briefly re-animated, all thanks to the neurological effects of L-dopa. Although this reprieve was short-lived it highlighted the powerful effect this drug could have.

More than 40 years later L-dopa is still a headliner in the world of neurodegenerative medicine. It is the main treatment administered to individuals diagnosed with Parkinson’s Disease (PD), who like Dr Sacks’ patients present with a rigid paralysis. PD is a disorder of the brain, caused by the loss of a particular set of nerve cells called dopaminergic neurons. These neurons communicate with other neurons through the release of a chemical transmitter called dopamine.

In PD the levels of dopamine in an area of the brain called the basal ganglia are reduced to such an extent that patients show neurological defects. The basal ganglia are important in controlling movement and as such the defects seen in PD patients include; slowness and loss of movement, muscle rigidity and resting tremours. Back in 1969 when Dr Sacks was testing the waters of L-dopa on his small group of encephalitis survivors, this drug was already gaining favour in the treatment of PD.

PD has been known about in the medical community since the early nineteenth century. However public awareness of this disease has only soared in more recent years, through the face of celebrity – or rather the faces of celebrity – ‘fly like a butterfly, sting like a bee’ Muhammed Ali and ‘Back to the Future’s’ Michael J Fox. Both of these men have been diagnosed with PD and have brought knowledge of the disease to a wider audience. PD is currently incurable, but charities like the Michael J Fox Foundation for Parkinson’s Research, are aggressively pushing forward the fight against this disease. Whilst those affected by PD press on with their own personal battles, the international scientific community is digging deeper into how best to treat the disease.

The beneficial effects of L-dopa on PD are unfortunately only transient, much like it was for the encephalitis patients portrayed in Awakenings. In addition to its temporary effectiveness, continued use of L-dopa can itself result in abnormal, involuntary movements. This drug however is still one of the best weapons we have in our arsenal against PD and as such is the focus of intense research.

Recent research efforts into L-dopa treatment

Last month an international group of researchers published findings addressing the problems associated with L-dopa treatment in PD (Ahmed et al, Science, 2010).

L-dopa, like naturally occurring dopamine which is lowered in the brains of PD patients, binds to proteins on the surface of neurons called dopamine receptors. This binding turns these receptors on and allows the neurons to send signals all around the body to initiate movement. Too much L-dopa means that these receptors are turned on too often, for too long and in an unregulated manner. The end result being involuntary movements. Once these receptors are turned on, a family of proteins called GRKs (G-protein linked receptor kinases) are known to be involved in switching them back off.

In this recent study rats affected by PD were treated with L-dopa and began to exhibit the involuntary movements previously mentioned. However when levels of GRK6 (G-protein coupled receptor kinase 6) were raised in the brains of these rats the involuntary movements were significantly decreased.

Importantly, this didn’t prevent the anti-PD effects of L-dopa and in some instances actually prolonged the effectiveness of this drug as a treatment against PD. As with all bench research the challenge remains to translate such hopeful findings into the clinic. So the fight against PD continues on into the next round…