Ketamine?

[kaypeeoh]

Levodopa, a standard Parkinson’s therapy, is a precursor molecule that is converted to dopamine in the brain. It is well-known for controlling Parkinson’s disease symptoms such as rigidity and slowness of movement.

However, prolonged use of levodopa may result in spontaneous involuntary movements — a condition called dyskinesia.

PharmaTher recently received a U.S. Notice of Allowance on its patent application for ketamine as a potential treatment for Parkinson’s disease and other motor disorders.

Ketamine (sold as Ketarx) is approved by the U.S. Food and Drug Administration (FDA) as an anesthetic and pain reliever.

Investigating Ketamine for Parkinson’s dyskinesia

In Parkinson’s disease, the results of a previous Phase 2 trial (NCT04912115) indicated that low-dose ketamine — which, unlike higher doses, does not induce anesthesia — reduced dyskinesia in patients with the neurodegenerative disorder.

Now, results from the Phase 1/2 clinical trial confirmed that ketamine is safe and well-tolerated. The medication also was found to promote a reduction of dyskinesia in treated patients for at least three months.

The trial was an open-label study to test the safety, tolerability, and pharmacokinetics — i.e., the process of absorption, distribution, metabolism, and excretion of a compound — of low-dose ketamine as a treatment for dyskinesia induced by levodopa. The study also aimed to find the effective dose to use in patients.

A total of 10 people with moderate to advanced Parkinson’s were enrolled in the study. The participants received two ketamine intravenous (into-the-vein) infusions within one week. The dose used was 0.30 mg/kg/hour, for five hours per infusion. Nine patients completed the infusion schedule.

Results showed that the maximum tolerated ketamine infusion rate was 0.20-0.30 mg/kg/hr. These doses were not associated with discomfort due to hypertension, also called high blood pressure, or dissociation. Dissociation is a common side effect of ketamine in which patients enter a mental state where they are less aware of their surroundings and start to feel disconnected from the body.

Dyskinesia decreased 51% during ketamine administration, 49% at three weeks after treatment, and 41% at three months. This effect was measured by the Unified Dyskinesia Rating Scale (UDysRS), a scale developed to evaluate involuntary movements.

Ketamine also had effects on Parkinson’s symptoms as assessed by the Unified Parkinson’s Disease Rating Scale (UPDRS). The UPDRS is the most widely applied rating scale to assess Parkinson’s severity and progression.

During ketamine infusion, UPDRS was reduced by 27%. The reduction at three weeks was 28%, and at three months after treatment it was 5%.

No adverse events after the treatment were reported.

“Our results provide further support for the repurposing of sub-anesthetic ketamine for individuals with [levodopa-induced dyskinesia],” the researchers wrote.

Based on these data, PharmaTher is planning a Phase 3 clinical trial to allow Ketarx approval by the FDA for Parkinson’s treatment under the 505(b)(2) regulatory pathway. This procedure is a new compound application based partially on previous studies, and offers a faster route for approval compared with traditional regulatory pathways.

“We are now focused on obtaining an agreement with the FDA to pursue approval under 505(b)(2) regulatory pathway with a potential Phase 3 clinical study for ketamine in the treatment of levodopa-induced dyskinesia in patients with Parkinson’s disease,” Chianelli said.

Ketamine also is believed to have a positive impact in pain relief and to offer additional benefits in easing depression, another frequent symptom in Parkinson’s patients.

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[Sydney75]

We are seeing a practice tomorrow that specializes in pain. I will ask if they are using ketamine for PD and report back. This is assuming Hurricane Ian does not result in a cancelled appointment, we are on the other coast but you never know.

[kaypeeoh in reply to Sydney75]

I became interested after reading that ketamine can treat depression that doesn't respond to standard medication. Being in a medical field I had easy access to ketamine and experimented with it.

[bbc680 in reply to kaypeeoh]

Thanks for the info, kaypeoh. What were the results of your personal experimentation?

[KatQ]

Your post says the "dose used was 0.30 mg/kg/hour, for five hours per infusion." Do you have any sense for how this would compare to low dosing the 25-50mg sublingual kind that can be mailed to someone for depression? I tried to do the math and it seemed like I did something wrong trying to convert the IV amount because I got 0.002mg over 5hours for a 160 lb person. That seems too low unless the IV does is smaller because its going right into your blood.

I am just wondering because you can now get ketamine therapy sent to your home, my friend did it for depression and I was thinking if that was enough my Dad (who had PD) could try it out. There was a VA clinical trial in our area for ketamine and they are studying if it will reduce inflammation in the brain for PD as well as depression. I didn't even know about it helping with Dyskinesia, so thats really exciting too!

[kaypeeoh in reply to KatQ]

It's a controlled drug so you'd need a doctor's prescription to have it mailed. The doc would have the right dose for IV.

[KatQ in reply to kaypeeoh]

Can the oral dose ever compare to the IV? I guess that is more of my question. Do you think taking the low dose orally could have any of the same benefits as the IV? I don't see any doctors being willing to prescribe him an IV unless he does the clinical trial. Also, I think it might be too much for him because after a hernia surgery it took him forever to wake up and get back to normal from the anesthesia, like 3 days.

[kaypeeoh in reply to KatQ]

I used to squirt the injectable ketamine into the mouths of feral cats as prep for spaying. I found giving it that way required a much larger amount than the IV dose.

[KatQ in reply to kaypeeoh]

Interesting, thanks so much!