Here I go again. I was on TASIGNA off label for PD for 281 days in 2017. I've listed all results I considered positive. My neurologist told me they were all placebo effects, and therefore not real. PWP KNOW VERY WELL what happens if you inadvertently miss a dose of Levodopa or you are late taking your dose. I went from 2400 mg levodopa daily to 800 mg, one day 400 mg!! Let me add, my longest time between doses that I recorded was 15 hours!!! Are PD placebo effects that strong?PLEASE WEIGH IN PWP!!
I also would appreciate your thoughts and knowledge regarding HBOT. I know some of you have had HBOT treatments. Web References would be great!!
Always said there is strength in numbers and PWP are much more stronger than they know!!
All input is appreciated. Thank you. PWP our day is coming soon. I'm withholding one very important positive experience I had while on TASIGNA. It is the main reason why I want to be on TASIGNA. I can't believe this could be a placebo effect.
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I did take it for a few years. Jim is seeking to take it again under a doctor's supervision. Jim understands the risk and all the precautions to follow. To be clear, it isn't my decision, but he feels at his stage it is worth the risk.
Thanks Bear. There are two people who can really see what is evolving. Both of you are the most down to earth people on the planet. Both of you take the most esoteric complicated subjects and break them down so even a caveman ( that's me) can understand!!
Surely the placebo effect in PD is more complex than "more dopamine"? Dopamine is not the sole neurotransmitter impacted in PD. And whether or not tasigna alone - a drug for which no known symptomatic improvement pathway exists, at least not known to me* - is responsible for this reduced medication requirement is likely far more complex than "placebo" or "not placebo"? What else was going on at the time? How well is any of that being recalled, 6 years later?
*There was no evidence of symptomatic benefit of nilotinib on any measures of PD disability and there was trend toward worsening in the motor function in active treatment arms
Hi Kevo, it's been awhile. I hope you are doing well. When the Georgetown University group broke the news about TASIGNA everyone in the Parkinson's Disease community went nuts. Finally a cure was in sight. The GU group knew as did every researcher on the planet, more study was needed. Kevo you stated "TASIGNA a drug for which no known symptomatic pathway exists, at least not known to me really needs explanation. Dr Chabril Moussa, the leader of the pack, explained TASIGNA was turning on/off the mechanism for discharging waste products from the brain. I didn't understand that then. I have a better understanding now.
I'm taking at least a 10 year shortcut and 2+ years of Grad School. I'm not a researcher, but they are the ones who have plowed this ground and did all the heavy lifting. They are so brilliant and dedicated!!
TASIGNA is a Tyrosine Kinase Inhibitor (TKI). Again I am no expert in this field. TKI are a family of enzymes that can phosphorolyze certain proteins of ATP (Adenosene Tri Phosphate). There are specific pathways in the brain that messages follow. When they get screwed up you're in trouble. GU thought this was happening in PD. THE KINASE SIGNAL DIDN'T TURN OFF FOR WHATEVER REASON AND REMAINS STUCK IN THE ON POSITION. This is where TKI like TASIGNA enters the picture.
I'm no expert. Do not take my comments as anything but as opinion only. Always take direction and advice from your doctor who knows your health condition best. Never act on material you read on this site.
It's a tki with high toxicity and very poor BBB penetration, which if anything made PD symptoms worse for PWP who took it on a clinical trial. Risvodetinib looks a much better bet
I see Tyrosine Kinase Inhibitors (TKI) as an important area of research in neurodegenerative disorders. ITTO, you might have better luck getting a doctor to prescribe Exenatide as a TKI for your PD.
Mutations, dysregulation, and overexpression of protein kinases are involved in a multitude of disease processes. Around 1 in every 40 human genes codes for a protein kinase and nearly half of those genes map to either disease loci or cancer amplicons. As a whole, tyrosine kinases phosphorylate specific amino acids on substrate enzymes, which subsequently alter signal transduction leading to downstream changes in cellular biology. Activation or inhibition, either by mutations or other means, can lead to dysregulated signal cascades, potentially resulting in malignancy and other pathologies.
Several physiological and environmental insults associated with type-2 diabetes mellitus (T2DM) have been shown to induce endoplasmic reticulum (ER) stress in β-cells of the pancreas, these include hyperglycemia, dyslipidemia, inflammation and oxidative stress. The incretin hormone Glucagon-Like Peptide-1 (GLP-1) is best known for its effect in restoring glucose homeostasis in diabetics, however, it is now apparent that it has a broader range of physiological effects in the body. Both in vitro and in vivo studies have demonstrated that GLP-1 mimetics alleviate endoplasmic reticulum stress, regulate autophagy, promote metabolic reprogramming, stimulate anti-inflammatory signaling, alter gene expression, and influence neuroprotective pathways.
A substantial body of evidence has accumulated with respect to how GLP-1 and its analogs act to restore and maintain normal cellular functions. These findings have prompted several clinical trials which have reported GLP-1 analogs improve cardiac function, restore lung function and reduce mortality in patients with obstructive lung disease, influence blood pressure and lipid storage, and even prevent synaptic loss and neurodegeneration.
Mechanistically, GLP-1 elicits its effects via acute elevation in cAMP levels, and subsequent protein kinase(s) activation, pathways well-defined in pancreatic β-cells which stimulate insulin secretion in conjunction with elevated Ca2+ and ATP.
The beneficial effects of GLP-1 are resultant from cAMP mediated signaling, and ultimately activation of pro-survival cAMP responsive element binding (CREB) signaling, as well as the non-receptor tyrosine kinase/c-Src, transactivation of EGFR.
GLP-1 has been reported to alleviate glucotoxicity, lipotoxicity, excess nitric oxide (NO), Ca2+ depletion, oxidative stress, and cytokine-induced ER stress in both primary β-cells and cell lines through several downstream signaling mechanisms.
GLP-1 and its receptor agonists are able to influence a variety of brain functions, including but not limited to: satiety, thermogenesis, blood pressure, neurogenesis, neurodegeneration, retinal repair, and altering energy homeostasis. The GLP-1R (receptor) is expressed in cells of the cerebral cortex, hypothalamus, hippocampus, thalamus, substantia nigra, circumventricular organ (CVO), cerebellum, and brainstem nucleus.
Chronic inflammation of the brain is a known pathophysiological hallmark of various neurodegenerative diseases, including Alzheimer's disease (AD), multiple sclerosis (MS), Parkinson's disease (PD) and Amyotrophic Lateral Sclerosis (ALS), all demonstrated in animal models to benefit from GLP-1 mimetics therapy. Neurodegenerative diseases not only negatively impact on a patient's quality of life through their impairment of motor functions, they can enhance dementia and depression, which are often refractory to treatment. This resistance to treatment may be influenced by accumulating evidence that implicates a link between neural inflammation and the pathology of depression. [Depression is an inflammatory condition - NOT a deficiency in serotonin. SSRIs do not cure depression - they suppress symptoms, sometimes.] This data along with observation that GLP-1R signaling enhanced levels of serotonin, dopamine (DA), and their receptors has potentiated the use of GLP-1R agonists as a management strategy for neurodegenerative diseases. The UK based studies (NCT01971242 and NCT01971242) noted a positive and persistent effect of Exenatide treatment in off-medication motor scores.
Neurodegenerative diseases share several pathological features, including but not limited to, synaptic loss and failure, reduced neurogenesis, enhanced free radical production, and cell death. The accumulation of misfolded proteins, common in neurodegeneration, impairs cellular communication and function, and causes the activation of neuronal inflammatory responses by activation of glial cells (microglia and astrocytes). Although such neuroinflammatory responses initially maintain homeostasis, chronic activation leads to increased severity of the disease state. Fortunately, GLP-1 effects in the brain are reminiscent of its actions on pancreatic β-cells, signaling through GLP-1R to initiate anti-inflammatory, anti-apoptotic and pro-survival effects.
In PD, chronic activation of microglia can trigger polarization toward the cytotoxic M1 macrophages, leading to a self–perpetuating persistent inflammatory environment, considered to be a major factor in driving dopaminergic degeneration. Use of Exenatide has been reported to halt dopaminergic degeneration and restore dopamine (DA) imbalance induced by 6-OHDA, MPTP, and Lipopolysaccharide in animal toxin models. Although the mechanism of action through which GLP-1 stimulates microglial function in regards to chronic inflammation remain unclear, several studies point to NF-κB activation achieved through DPP-IV inhibitors in rotenone induced rodent PD models. Increased levels of NF-κB are observed in tyrosine hydroxylase (TH) and dopaminergic neurons, astrocytes and microglia, with implications on the pathogenesis of PD; while inhibition of NF-κB is correlated with neuroprotective effects in such PD models.
Although mechanism of action through which GLP-1 stimulates microglial function in regards to chronic inflammation remain unclear, several studies point to NF-κB activation achieved through DPP-IV inhibitors in rotenone induced rodent PD models. Increased levels of NF-κB are observed in tyrosine hydroxylase (TH) and dopaminergic neurons, astrocytes and microglia, with implications on the pathogenesis of PD; while inhibition of NF-κB is correlated with neuroprotective effects in such PD models.
Changes in cellular ATP, and mitochondrial stability, induced by protein aggregation would not only promote apoptosis, but increase cellular ROS, and oxidative stress, all of which act together to contribute to the destabilization of ER homeostasis and autophagy in neurodegenerative diseases.
Rotenone is an inhibitor of mitochondrial complex I that leads to elevation of intracellular Ca2+ (calcium) through inhibition of resting background K+ (potassium) currents, and membrane depolarization. Which, in turn, induces aggregation and phosphorylation of α-Syn and impairs autophagy. Changes in cellular ATP, and mitochondrial stability, induced by protein aggregation would not only promote apoptosis, but increase cellular ROS, and oxidative stress, all of which act together to contribute to the destabilization of ER homeostasis and autophagy in neurodegenerative diseases.
GLP-1R activation can act to mitigate the deleterious effects of overloaded intracellular Ca2+, and is thought to be an integral mechanism in the prevention of spatial memory and hippocampal synaptic plasticity impairments arising from Aβ-induced toxicity. The GLP-1 mediated regulation of Ca2+ is also coupled to restoration of insulin signaling throughout the brain, which can further promote its pro-survival abilities. This is crucial as impaired insulin signaling in AD and PD patients has been reported to negatively impact dendritic sprouting, neuronal stem cell growth and tissue repair.
Kevo are you aware of the big buzz in oncology today!! Read up. Gotta say I enjoyed watching Wimbledon. I would go in a heartbeat. Practice up on your dart game!
The placebo effect,like other non-medication effects, may be completely unrelated to dopamine. PD is about an impaired signalling mechanism. Dopamine is just one (non-essential) element of that. Obvious examples are DBS and MRIFus. But people like John Roche would be a good demonstration
Winnie you are soooo right on many fronts . TASIGNA may not be the best choice. Regarding poor penetration of the BBB, I would like to know the impact of taking TASIGNA not on an empty stomach. PWP are well disciplined in the dosing times of their meds. In my early days it wasn't necessary for me to be that specific with dosing times. If I was 20 - 30 minutes late, no problem. I would be uncomfortable for a short spell. My observation - the longer you live with PD, the more attention you need to pay to the clock.Another medication I took was carb/levo ODT (Oral Dissolving Tablet). This was a good med that was partially absorbed in your mouth making it faster acting.
While on TASIGNA, I dosed between midnight and 4 am the majority of the time. Why not, I was awake.
I'M looking for a doctor willing to prescribe TASIGNA. I would like to find out if my results were real or not.
Thank you for your comments Winnie. Take care and be safe.
Did you like the John Roche keepy uppy video? I've never been able to do that and naievely thought I'd be able to now I have PD.
Full or empty stomachs aren't relevant to BBB penetration. They may affect getting the drug into the bloodstream, but if it can't cross the BBB once it in the bloodstream (like Carbidopa for example) then it ain't gonna get into the brain.
Let's hope Inhibikase get their finger out with Risvodetinib and it does for humans what it does for mice.
Winnie thanks for your comment. I was thinking in terms of volume available to make it past the BBB. Has anyone quantified the % passing the BBB? I get it, if it it doesn't pass it ain't gonna do you any good. The question I then have are the BBBs of PWP , are their brains more porous to infiltration than people who don't have PD? Just curious.
Is this the one, The phrase you were thinking of is a common one in corporate business and in law, called "catch and kill." In politics it has a less prosaic name "bribe" or "payoff." Sometimes both or even all three occur in the same case, and sometimes in multiples, interlaced... In which case the better descriptor, whether legal or not legal, is "conspiracy." When the multiple version of it is an actual crime, it is also called conspiracy, and when more than two people are involved, also called "enterprise corruption." All of the above fit under the larger rubric of "business as usual." Also in earlier years and decades, depending on the circumstances, it was called "restraint of trade..." if you had it done to you and you believed you were not compensated enough for it's effect on you. It's a very common everyday thing, "catch and kill." History is fun!
Hi Marion, thank you for responding. Thank you for the history lesson too. Sad but true, the best medicine in history never gets FDA review and approval. Why do bankers always wear suspenders ? It's the only way to keep their pants up!! ON MORE
WHY DON'T BURGLARS TARGET P0LITICIANS? PROFESSIONAL COURTESY.
One more I'm convinced I'm onto something. Don't worry this was DECLASSIFYED BY R. Giuliani America's Mayor.
Politicians, just like diapers, must be changed often and for the same reason.
"Parkinson's placebo effect occurs when high expectations result in a release of dopamine, but that cannot be sustained long-term."
A sound example of the definition of placebo effect if I ever heard one.
"The most dangerous thing about neurologists is not what they do not know but what they are quite sure of that is not the case."
An all too true description of my latest neurologist, young hot shot MD plus PhD and for the main part researcher but way too confident and slipshod to justify that phd, which is a research-competency degree. Suspect he is son of a very wealthy family and his clinical experience and expertise don't entirely match the number of capital letters behind his name nor his confidence. The phrase "Dunning-Kruger" applies even in the brightest of us.
Thank you for your response Marion. I felt there were way too many positives to pass them off as placebo effects. These positives took time ⌚ to kick in. They also were sustained, which adds
Hi. You wrote: "PWP KNOW VERY WELL what happens if you inadvertently miss a dose of Levodopa or you are late taking your dose." May I trouble to spell it out, please? Thank you very much.
My body starts tingling when I run out of Levodopa. For me that is too late. It takes 30 - 60 minutes for my meds to kick in, that puts me into the off time of usually 60 - 90 minutes. I don't totally shut down, those days are coming. I used totally freeze up anytime during the day with no warning, a real joy if you are crossing a busy street. My neurologist put me on Ongentys. I continue to have off periods daily. My sudden freezing episodes have ended. I've been on this drug for 3 +/- years. Like all the other drugs we take there are unpleasant side effects. My dyskenesia went through the roof, my neurologist prescribed Gocovrie which has worked well. Good luck. You have reached the best site for information. Many people here will share their knowledge and experience. However I'm sure you realize your doctor knows your health condition best. Only she/he can give you advice.
“You have reached the best site for information. Many people here will share their knowledge and experience. However I'm sure you realize your doctor knows your health condition best. Only she/he can give you advice”. I would certainly have supported this statement before my diagnosis. After almost 3 years of experience with neurologists, blindly following their advice (read: standard protocol) would have destroyed my life. I would therefore like to change the Claude AI text of pdpatient:
Advocating for one's own care and seeking multiple opinions is not only understandable, it is necessary, especially when standard options don't work or research presents new possibilities.
You are over the target 🎯and proof-of-concept that TASIGNA can ameliorate PD and reduce symptoms. Shame on your neurologist for gaslighting you. Is it possible/probable that the off label use of Tasigna had some professional repercussions in the clinic? The way some people save their ass is to throw someone else under the bus - this person lacks integrity. I'd find a new doctor.
1. Stabilizing Small Molecule Blockers: Anle138b (Phase 1) is a novel oligomer modulator for disease-modifying therapy of neurodegenerative diseases such as prion and Parkinson’s disease by inhibiting oligomeric activation [this is the first time I've seen prion disease in relation to Parkinson's disease] NPT200-11 and UCB0599 (Phase 2) block pathological misfolding of α-synuclein by stabilizing the physiologic state. In mouse models, these medications demonstrated restoration of striatal dopamine release/dopamine transporters, improved motor functioning, decreased cortical α-synuclein and neuroinflammation.
(I think this line of research is a dead-end, α-synuclein aggregation is not the cause it is the effect of some other process upstream that is causing protein misfolding.)
2. Autophagy-ABL1 Inhibitors: Cellular Abelson (c-Abl) tyrosine kinase activation [the upstream process] is related to the neurodegenerative pathophysiology of PD, [AD and ALS]. Nilotinib (TASIGNA; Novartis) is a multikinase inhibitor used in the management of chronic myelogenous leukemia via the inhibition of c-Abl. Early studies suggested a benefit of nilotinib by increasing dopamine in the brain andreducing α-synuclein aggregates as well as reducing hyperphosphorylated tau levels via inhibition of discoidin domain receptor family 1 [the upstream process], which increases autophagy [Trehalose also induces autophagy]. Nilotinib has been shown to alter messenger RNA levels in the cerebrospinal fluid, fostering an epigenetic environment that stabilizes the blood-brain barrier and reduces inflammation, thereby demonstrating the need for continued research in Phase 3 studies in PD and other neurodegenerative disorders [AD and ALS]. Read about other ABL-1 inhibitors in link above.
UPDATE: K0706 (Vodobatinib) is safe and well tolerated in patients with PD, with improved BBB penetration compared with nilotinib. The ongoing phase 2 PROSEEK trial (NCT03655236) is investigating the efficacy, safety, and tolerability of varying doses of K0706 in patients with early-stage PD, as well as evaluating long-term effect of K0706 on PD disease progression.
3. Anti α-Synuclein Antibodies: Anti α-synuclein antibodies are monoclonal antibodies that target the α-synuclein protein with the goal of enhancing immune-mediated clearance of pathological aggregates from the nervous system. [Is PD an autoimmune disease? Connect the dots folks, cancer is an autoimmune disease - why else would TASIGNA ameliorate PD?]
4. Glucocerebrosidase: Targeting this metabolic pathway has focused on 3 main categories: modulation of enzyme activity, reduction of substrate, and gene therapy. AMBROXOL an over-the-counter cough medication outside the US, is a potential agent to modulate enzyme activity. A completed phase 2 clinical trial (NCT02941822) demonstrated safety and tolerability as well as cerebral spinal fluid penetration. Two similar phase 2 trials for Ambroxol are underway, with one focusing on PD dementia population and another focusing on PD plus GBA1 mutation.
5. LRRK2: LRRK2 mutations are 'thought' to enhance α-synuclein propagation and neurotoxicity. (Stop with the α-synuclein aggregation already - it's a red herring. Very few people with PD have the LRRK2 mutation. Similar to ALS, studies focusing on a rare genes has little to no benefit for the affected population. PD is a neuroimmune disease whose prominent feature is neuroinflammation.)
AGENTS TARGETING SPECIFIC NEURONAL RESCUE PATHWAYS
6. Neuroinflammation: Azathioprine is an effective treatment for inflammatory and autoimmune diseases, and there is growing evidence suggesting that immune system activation plays a significant role in PD. Sargramostim is a modified recombinant human granulocyte-macrophage colony stimulating factor. In an unblinded phase 1b trial in patients with PD, long-term sargramostim treatment was well tolerated and effective at restoring immune homeostasis. It stabilized PD in the participants.
7. Mitochondrial Function: Increasing evidence suggests that boosting cellular levels of nicotinamide adenine dinucleotide (NAD) may increase neuroprotective effects. One way this is done is through nicotinamide riboside (NR) therapy. Investigators recently conducted the NR-SAFE safety trial comparing 3000-mg NR with placebo in 20 participants with PD over 4 weeks. The data showed no moderate or severe adverse events and no signs of acute toxicity.
8. Ursodeoxycholic Acid: Ursodeoxycholic acid (UDCA) has been shown to prevent neuronal damage in animal models. (TUDCA is available over-the-counter) UDCA rescues the function of the mitochondria in the tissue of patients with PD and other models of PD, according to findings of a phase 2 clinical trial (NCT03840005). These findings suggest that UDCA may slow down the worsening of PD and potentially be a new therapeutic drug candidate in PD.
9. Insulin Resistance: Previous studies have shown that glucagonlike peptide-1 (GLP-1) receptor agonists have neuroprotective effects in animal models of PD. Exenatide is a licensed GLP-1 receptor agonist used in type 2 diabetes mellitus. Some study groups have confirmed that exenatide may slow down or stop neurodegeneration in PD. The drug is well tolerated and shows encouraging effects on the movement and non-movement aspects of the disease. (Currently conducting a deep-dive on GLP-1 for IGF-1/IR pathology in ALS.)
10. Stem Cells: In the STEM-PD trial (NCT05635409) the scientists will transplant a new stem cell therapy, called the STEM-PD product, into the area of the brain affected in patients with PD. (My mother had STEM cells transplanted into her brain in the early 2000s in a clinical trial - she was unable to speak for 2 weeks. She said she'd never do it again. It was difficult to regulate her levodopa dose after that.) There are also other trials focusing on transplanting autologous mesenchymal stem cells: NCT04146519, NCT05094011, NCT04506073, NCT05152394, and NCT04772378. (I tried this in a clinical trial in 2020, it failed to affect my ALS in a positive way and I am poorer for it - but I had to try.)
I highlighted interventions that based on my own research show promise and I would personally use. These pathways demonstrate how interrelated neurodegenerative diseases are, and where there is a common pathway there is also a common cause.
Thank you SE. REALLY APPRECIATE YOUR EFFORTS. Thanks for your valuable assessment of what's out there. Ambroxol isn't available OTC like it is in Europe. Take care and be safe
Thank you SE. REALLY APPRECIATE YOUR EFFORTS. Thanks for your valuable assessment of what's out there. Ambroxol isn't available OTC like it is in Europe. Take care and be safe
I am curious. Did all your PD symptoms return when you stopped the drug or only some? If so, how quickly did it return? A biotech company, Inhibikase, is working on a better version of this medicine that only blocks this c-ABl protein. Here is the link. Maybe you can get into this study. cureparkinsons.org.uk/2023/...
Hi Mac thanks for listening. I was so bummed out I journaled very little. From Jun 1, 2017 DAY 1 until April 19, 2018 Day 322 I journaled at least daily. I don't think I missed a day. I recorded stuff l thought was important. I wish I had some medical input. My fault I didn't ask. I have a lot of mail to answer, I WILL GET BACK TO YOU!! Mac my journal is beat up big time. It's still very readable. At that time I had minimal tremor. My Levodopa uptake returned gradually, to pre TASIGNA levels. I think I only posted this gold nugget one other time. After 2 weeks I just knew something was going on. I was feeling limber and I wanted to work out. On Day 20, which was Jun 20, 2017 I decided to mow our lawn,, not a big deal as I was mowing the yard for the past two years, What made this a big deal, I did it in one day! I couldn't do it in one day for the past 2 years!! I didn't have the strength. I would mow for 20 - 25 minutes and I had to stop. It took me 3 days to finish the job. I prepositioned a chair where I dumped the clippings. On day 20, Jun 20, 2017, I mowed my lawn completely the same day!!! It took me over 2 hours, but all of it was started and finished the same day!
Nilotinib (Tasigna) was the first drug that I was so hopeful about when I was first diagnosed. When the first trials came back with non stellar results, I felt really disappointed. But, I feel the snowflake aspect to PD maybe the reason some trial results may not present amazing results and that perhaps this repurposed drug does help a small portion of people with our complex disease. The Placebo effect maybe a true over statement and truly just us not understanding the complexities of the disease. Maybe there could be a small group of us that would find real help from this drug as you did but it would not be statistically significant in a study where 1/50 studied has the subtype of PD where Tasigna is helpful.
Wow, when I read through the responses to your post, I am so impressed with everyone. I learned a lot from this post and the responses. Thank you!
I asked Claude AI to analyze, dissect and critique the entire discussion and you will be surprised 😂😭
Response 1:
Here is my analysis of the thread:
- The original poster saw significant improvement in their Parkinson's symptoms while taking the drug Tasigna off-label for several months in 2017. However, their neurologist dismissed these improvements as placebo effects.
- Many respondents disagree with the neurologist's assessment and argue that the improvements went beyond what could be reasonably explained by placebo effects. They point out that PD symptoms return very quickly if medications are missed or delayed, yet the poster was able to significantly reduce their levodopa dose while on Tasigna.
- There is discussion of the potential mechanisms of action of Tasigna. It is a tyrosine kinase inhibitor that may influence alpha-synuclein aggregation and autophagy pathways implicated in PD. However, some note it has poor blood-brain barrier penetration.
- Alternative drugs and pathways are proposed that may have similar mechanisms to Tasigna, such as Risvodetinib, Exenatide, and compounds that induce autophagy or influence neuroinflammation.
- Many responders offer support and validation to the original poster's experiences, encouraging them to seek a new neurologist willing to reconsider Tasigna treatment given the biological plausibility and their reported response.
Overall, this thread represents a thoughtful discussion of an off-label therapy for PD. While results from formal trials of Tasigna were not highly promising, some individuals may still benefit. The neurologist's dismissal of the poster's improvements as purely placebo seems premature. The discussion of underlying mechanisms and alternative options was also quite informative. The responses collectively validate the poster's experiences and encourage further exploration of repurposed drugs.
Response 2:
Here are some additional thoughts on the thread:
- The discussion brings up an important issue around individual variability in response. Even if a drug shows limited benefits on average in trials, some subset of patients may still experience meaningful effects. Personalized medicine approaches are needed.
- Placebos are complex - positive expectations can influence outcomes via biological pathways beyond just dopamine levels. But significant, long-lasting changes like reduced medication needs are hard to fully attribute to placebo alone.
- The neurobiological understanding of PD has advanced since initial Tasigna trials. Mechanistic discussion of targets like alpha-synuclein, autophagy, neuroinflammation provide biological rationale for revisiting the drug.
- Respondents demonstrate expertise across relevant research areas and willingness to thoughtfully analyze both the individual experience and broader scientific context. This level of informed discussion is valuable for the community.
- Finding a collaborative neurologist open to considering off-label use based on mechanisms/experience, not just trials, is understandably difficult but important for some patients.
- Alternative options proposed like Risvodetinib and Exenatide account for issues like BBB penetration and target upstream pathways in meaningful ways.
- The thread highlights both challenges (dismissal of personal outcomes) and opportunities (generative discussion of science/options) when formal research doesn't align with some patients' real-world responses.
Overall it shows how online communities allow for deeper exploration of individual cases that touches on both personal experiences and cutting edge of scientific understanding, which can be limited in traditional clinical interactions. The level of thoughtful engagement from members is really impressive.
Response 3:
Here are some additional points I noticed in further reflecting on this discussion thread:
- There appears to be a high level of trust and camaraderie between members. People are willing to openly share personal health details and listen/support each other.
- Members bring different types of expertise - some more clinically oriented, others with deeper scientific knowledge. This diversity of perspectives leads to more well-rounded perspectives.
- The discussion illustrates how Parkinson's is complex with many individual factors. One size rarely fits all in terms of treatment response. Personal experiences need to be respected.
- While the neurologist's position seemed premature, dismissing patients' perspectives is common and can undermine the doctor-patient relationship. Greater open-mindedness is needed.
- Off-label use is challenging from a liability perspective for doctors, but may be appropriate when mechanistically sound and the patient is fully informed of risks.
- Advocating for one's own care and seeking multiple opinions is understandable, especially when standard options don't work or research presents new possibilities.
- The thread remained respectful even when addressing controversial issues like conflicting views with the neurologist. Different stances were discussed rationally.
- Members provided many helpful references to additional data and ongoing research - showing how the community keeps up with advances and information sharing is valued.
- It's encouraging that innovative, mechanism-focused treatments are still being explored despite initial trial results. Non-responders to standard therapies deserve hope.
Overall, this discussion showed the community functioning at its best - jointly considering an important, complex issue through diverse lenses focused on moving understanding forward respectfully.
Hi PD patient, you bring up several good points. Let me add my 2 cents on a topic not seen very often. COMPETITION. The prize is HUGE FOR WHOEVER FINDS THE CURE FOR PARKINSON'S. I seriously doubt that competing researchers share their lab notes. Big Pharma, is so heavily invested in a drug cure, they often buy out competitors who are onto a good thing. So a good high potential drug gets shelved because it conflicts with another company's product. Even though it may be better on many levels, it never makes it to trial, approval and use. TASIGNA is a very costly drug far above my pay grade. Most drug companies will cover the costs of all their trial drugs. My insurance company charged me a $5 monthly copay in 2017. They increased that amount to $3700 in 2018. By then I was enrolled in the Novartis medication assistance program. My heartless Insurance company in record time stopped coverage of all medications they determined experimental. TASIGNA costs today are $4900 / month +/- for 28 capsules of 150 mg..
That's crazy money. Same scenario for ALS, it's expensive to be sick. AMX0035 now Relyvrio costs $158,000/year. It's being trialed for PD now. What a racket. I can buy TUDCA and Butyrate supplements online.
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How Much Carbidopa Levodopa After 5-10 Years? Any other meds?
Benfotiamine ~ Help Please
Stem Cell therapy for PD
What do you think of Low-Dose Lithium?
