1. Start with HIV-1s ‘country cousin‘, Equine Infectious Anemia Virus (EIAV). EIAV is a lentivirus, like HIV, so it is a good gene therapy virus. Lentiviruses are a bit more trustworthy than the gamma retroviruses (not as likely to cause insertional mutagenesis/cancer), plus the scientists made some modifications to the LTRs to keep them from accidentally over-expressing nearby genes.
2. Scoop out EIAVs genomic guts. Replace them with three genes essential for the production of dopamine: tyrosine hydroxylase, AADC, and cyclohydrolase 1. Get these three guys into a neuron, and you can get it to start producing dopamine again. This is another reason why a lentivirus (instead of all the other viral options we have for gene therapy) is a good idea. Instead of needing to deliver three separate viruses that express one of each of these three necessary enzymes, a lentivirus can fit all three genes into one virus. You know all three are going to get in the same cell, which is necessary for function.
3. Inject the resulting GMO virus at various doses (low, medium, high dose) into the brains of severe Parkinsons patients. Look, the virus needs to get into the brain. You can either inject the virus into the blood and pray to Xenu they get past the blood-brain-barrier and manage to infect the right cells, or you can jam the needle into the brain to make damn sure the virus gets where it needs to be. Its not pretty, but thats what we have to do with todays gene therapy technology.
4. Wait. See what happens.
So what happened?
During the first year after treatment, there were 51 mild adverse events, 3 moderate, no severe (well, there were some severe events, but they were unrelated to the gene therapy).
When the patients were on their normal meds, there wasnt any difference in the patients Unified Parkinson’s Disease Ratings.
When patients were off their normal meds, thats when things got interesting. Some of the patients didnt see much of a difference, but others saw up to a 61% drop in their score (higher scores are bad). When they looked at the 12 month time point (as far as the high dose patients had been so far), there was a lovely dose-response curve, with the low patients scores dropping ~8 points, the two mid groups dropping ~10 and ~12 points, and the high dose group dropping ~15 points.
When all patients were combined, there was an average drop in ~12 points in their UPDRS score.
While patients UPDRS scores dropped when they were off their normal medications, the ‘off’ scores were still way higher than normal. Baseline off-med scores were ~71. The therapy dropped it down to ~53 at 12 months. On their meds, the baseline scores were ~28, and Im assuming the goal is to have patients 1) off their meds, and 2) scores still way lower than 28.
This is a great first-step in gene therapy for Parkinsons… but this approach is *not* anywhere near a ‘cure’, yet. Great first-step, though. So freaking cool