There is good news from a company called NodThera who have been developing a drug that tires to address chronic inflammation and its relationship to a number of diseases including Parkinsons.
The early data means that there is now a "Priority development program underway in Parkinson’s disease" which was hoped for for one of their drugs, NT-0796.
The work on inflammasomes is being pursued by a number of companies. (in depth article here scienceofparkinsons.com/202...)
Does anyone else have other symptoms of chronic inflammation? I also have issues with CPPD.
More details:
"NodThera, a leading clinical-stage biotech developing brain-penetrant NLRP3 inflammasome inhibitors to treat chronic inflammatory diseases, today announces positive data from first-in-human studies of its lead therapeutic candidates, NT-0249 and NT-0796, and provides an update on the Company’s priority clinical development programme.
In the studies, both candidates were shown to clearly inhibit the NLRP3 inflammasome, a highly validated drug target that plays a pivotal role in controlling inflammatory diseases. The differentiated design characteristics of each candidate enabled them to penetrate different areas of the brain for optimal drug distribution in a range of NLRP3-driven diseases."
In terms of inhibiting inflammasome NLR3P, melatonin has shown that ability in multiple studies and melatonin has shown the ability to easily cross the blood brain barrier (BBB) while also being one of the most potent antioxidants in the body and has shown the ability to return elevated oxidative stress levels in PwP to healthy control levels at just 50 mg/day.
' Furthermore, melatonin decreased the expression of inflammasome components and reactive oxygen species (ROS) induced by LPS; co-incubation of melatonin with α-bungarotoxin (α-bgt) or luzindole abolished the anti-inflammatory and antioxidant effects. In vivo, melatonin reverted LPS-induced cognitive decline, reduced NLRP3 levels and promoted autophagic flux in the hippocampi of WT mice, whereas in α7 nAChR KO mice melatonin effect was not observed. These results suggest that melatonin may modulate the complex interplay between α7 nAChR and autophagy signaling. '
Melatonin Returns Oxidative Stress Levels In PwP To That Of Healthy Controls At 50 mg/Day For Three Months:
' These data suggest the existence of an active, persistent oxidative stress in PD. After three months of treatment with melatonin, the levels of lipoperoxides, nitric oxide metabolites, and carbonyl groups in proteins were lower than in the placebo group and were statistically similar to the levels of healthy controls. The activity of catalase was increased with the treatment with melatonin at levels similar to the control group. '
' One important characteristic of melatonin is its permeability into the brain. It readily passes through the blood-brain-barrier and accumulates in the central nervous system at substantially higher levels than exist in the blood. As a result, this molecule exhibits strong neuroprotective effects, especially under the conditions of elevated oxidative stress or intensive neural inflammation. '
In the above study it is shown that melatonin also has neuroprotective effects. Melatonin has a very good safety profile.
Melatonin also reduces endoplasmic reticulum stress in the brain to further afford neurodegenerative protective effects as discussed here :
' However, melatonin can reduce ER stress through methamphetamine toxicity by reducing the expression of the ER stress response genes and proteins [127]. '
' Therefore, melatonin can regulate neuronal cell death induced by ER stress under insulin resistance by reducing the ER stress in SH-SY5Y neuroblastoma cells [129]. '
' Melatonin can effectively downregulate the levels of ER stress molecules GRP78/BiP, CHOP, and caspase-12 proteins in kainic acid-induced N2a cells [130]. '
It is worth noting that melatonin has a very good safety profile.
Art
Melatonin returns oxidative stress factors to healthy control levels.
How do you know how much to take? Can you take it with other supplements? Thanks for all your information. You are so helpful to this group? I'm totally frustrated!
How much melatonin you can take varies from person to person. Some can barely tolerate 3 mg while I take 132 mg/night. Others take an even higher dose than me.
In the melatonin/ PwP studies, melatonin showed benefit at 10 mg/day and 50 mg/day.
Would like to know what Roche has done in that area after acquiring Inflazome a couple years ago. Have not seen or heard anything since. Sure they must have plans after spending almost 500 million to purchase that “small” biotech. Thought they were on the cusp of using that acquired technology to advance a novel Parkinsons treatment.
They are also trialing similar drugs for Ulcerative Colitis and Coronary Artery Disease. Presumably having 3 different drugs increases cost but reduces risk of total failure and increases revenue instead of off label use being denied by insurance....
It looks like the only clinical trial by Nodthera in the US that involves NT-0796 is in Miami, FL and Austin, TX and is for patients with obesity and risk of cardiovascular disease.
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