Considering that we've been talking about gene therapy a lot here lately, I think this news is quite relevant. Current Omnome topics aside, this news is very important.
There have been recent reports about a gene therapy strategy that resulted in symptom amelioration in Parkinson's patients. The project was spearheaded in part by Dr. Matthew During of Ohio State University. Having met Dr. During at the Society for Neuroscience conference in Orlando in 2002, I am not at all surprised that he would be part of a project that could stand at the cutting edge of clinical translational research. As a trained neurosurgeon with a PhD, this New Zealander came across as not only talented, but also as having major cojones.
So let's talk about the therapeutic that was tested by During and his colleagues. The researchers used an adeno-associated virus (AAV) to deliver a gene encoding the protein, glutamic acid decarboxylase (GAD), to the subthalamic nucleus in the brains of Parkinson's patients.
So what does that all mean? Well, let's briefly review AAV. AAV are small viruses that do not induce an immune response in humans. Additionally, they deliver DNA genetic material which directly incorporates into the cellular genome. It gets copied when transduced cells divide into daughter cells. Now we'll talk about Parkinson's Disease. Parkinson's is a complicated disease which results in neuronal death, neurodegeneration. Specific parts of the brain are very susceptible to this neurodegeneration. The substantia nigra of the brain is one of those parts. As a result the neurotransmitter balance is thrown off to the point where the substantia nigra is too "excited". The aim of a GAD gene therapy is to turn part of the substantia nigra from a primarily excitatory nucleus to a primarily inhibitory system.
Whether or not the gene therapy is working the way the researchers think it does is always up for debate. What isn't as debatable is the fact that most of the patients who received the injection of GAD encoding virus had symptomatic improvements. Since this was mainly a dose ranging and safety Phase I/II clinical trial, the number of patients was not high enough to power a statistically significant symptom amelioration metric. However, all signs point toward some hope for improved quality of life for Parkinson's patients. What this also provides is another glimmer of hope that gene therapy strategies might be in the clinic sooner than later. What this certainly is NOT is a cure. Patients need to remember that the neurons are still dying. Neurodegeneration is an extremely tough nut to crack (trust me on this one...I'm in neurodegeneration research for the long haul). Maybe one day we'll come up with a gene therapy that can protect the neurons...