Promising disease modifying therapies for PD

[Farooqji]

To date, there are no disease-modifying therapies that slow, halt, or reverse the progression of PD. Development of disease-modifying agents remains a high priority. Advances in understanding the molecular pathogenesis of neurodegeneration in PD, development of new animal models, and human dopaminergic neuronal cell culture systems together with the identification of new therapeutic targets (1) over the past decade have led to the initiation of exploratory clinical trials. In this 11th installment of Science Translational Medicine anniversary Focus series, it highlights promising agents that have the potential for altering the progression of PD and the science behind them

filebin.net/uecra4kzr5ekrxp...

[WinnieThePoo]

The more stones that get turned over, the more likely it is a cure will be found under one of them. Its encouraging there is so much going on. And that report wasn't exhaustive. It didn't include alpha blocker repurposing for one

[Farooqji in reply to WinnieThePoo]

Here is a complete list

smallpdf.com/shared#st=1147...

[MBAnderson in reply to Farooqji]

Thank you, iqbal. Very interesting.

[marnegro in reply to Farooqji]

Hi can you provide me the link again? The one you posted above said it’s expired. Thanks

[Farooqji in reply to marnegro]

filebin.net/ftzcfurv2wuk5mz...

[Hidden]

I will venture to speculate that Exenatide is possibly disease modifying. I have been on a variation of this class of medicine for the past few years and I am just now experiencing relief from a substantial reduction in my Sinemet/Rytary. Turns out that what my doctor and I perceived to be worsening of the disease wasn’t so. I was actually getting more and more dyskinetic.

My doctor won’t comment on my belief that the Exenatide is helping. But isn’t the requirement of less Levodopa a sign of less disease progression? My UPDRS scores have improved over the years, but then again the score is subject to the observation at a point in time.

The trouble is that the Neurologist community appears to be skeptical about the future of disease modification hope.

[Farooqji in reply to Hidden]

There are many examples (including other than PD as well) where doctors have proven to be wrong

[park_bear in reply to Hidden]

We are not required to buy in to their skepticism!

[Isthistheone in reply to Hidden]

Can you define what your substantial Sinemet reduction was?

JMO, I am not a doctor, isn't there some possibility that your Exenatide therapy has done more than stopping your PD progression? Where is the dopamine coming from if you are taking substantially less? Maybe your body is producing its own dopamine once again!!

WISHING YOU THE BEST!!!

Please keep us informed.

[Hidden in reply to Isthistheone]

God bless your heart, IsThisTheOne! I hope what you are saying is true and only time will tell.

In 2017, I was taking at least 8 Sinemet 25/250 mg Immediate release tablets per day. That is 2000 mg or 2g per day.

Between 2017 and middle of 2018, I was on Trulicity, which is Liraglutide, a cousin of Exenatide. The doctor reduced my dosage to 15 Sinemet 25/100 mg tablets per day, which is 1500mg or 1.5g per day.

At that time, I was not aware of the research and I was on Trulicity because of the recommendation of my diabetes doctor.

After, the bizarre fluctuations in my responses, my doctor switched me to Rytary and I was on as high as 3600 mg or 3.6 g per day. My doctor says that although there is no equivalent dosage comparisons between Rytary and Sinemet, he believes that Immediate release Sinemet is up to 4 times more potent/stronger than Rytary.

From April of this year, I am on Bydureon/Exenatide.

Now I am on a mix of Rytary and Sinemet. 10 25/100 mg tablets of Sinemet IR and 5 145mg Rytary per day. That is 1000 mg or 1g of Sinemet IR per day and about 800 mg of Rytary per day. I am applying the 4:1 ratio to Rytary and I have a total of 1200 mg of Carbidopa/Levodopa per day.

I think that is a substantial reduction in the medicine that I am taking now.

My UPDRS score is less than 25 on more than one visit. It has been up in the 80’s before.

[Isthistheone in reply to Hidden]

You were at 2,000 mg of L-dopa, and now you are down to 1,200 mg? Yes I would call that significant! Do you attribute that to Exenatide?

I started Tasigna on June 1, 2017 - 200 mg capsule once per day. I posted my outcome in a previous post. Long story short, I'm on 150 mg capsule once per day now. My daily intake of L-dopa was a little less 2,000 memory tells me 1800-1900. I had days whete I got down to 1,000 and some days 800, even 600! That was after 4 months of being on Tasigna. I always took T between 1201 and 2 am. Instructions were to take T on an empty stomach. Was always up at that time to Pee anyways. I routinely went 8-10 hours between doses, personal best was 15 hours! I did not crave Sinemet at all.

Bottom line my insurance company required preapproval before refilling. My doctor, god bless him, is elderly and suffering from cancer. He is too frail and doesn't

want to battle with them. It costs $6,000 per month for a 28 day supply of Tasigna. Insurance companies are not your friends.

Tasigna , IMO, absolutely works. I'm sure we are going to hear more from Georgetown. Again, JMO, they are the most knowledgeable people on the planet

regarding Tasigna and PD. If anyone has Hollywood's ear, i have an unbelievable story to tell. All of it is true.

[Hidden in reply to Isthistheone]

Wow! I am going to check out Tasigna. Yes, now that I am aware of the studies on Exenatide, I can only say that I don’t think that it’s a placebo effect.

[Isthistheone in reply to Hidden]

Not so fast

[Hidden in reply to Isthistheone]

I am seeing your responses to the other thread and my questions are answered. Thanks.

[alohacindie]

Check this out: ajmc.com/newsroom/common-pr...

My husband's doc prescribed it off label. To slow or halt? Why not?

[Isthistheone]

In year 2 of Tasigna (nilotenib) off label for PD. First year with 200 mg capsule once per day. Presently on 150 mg once per day (different MDs). My opinion, its worth the risk. I have tolerated Tasigna well, no issues.

I believe Tasigna is working. It has either slowed or stopped my PD progression. My belief on reversal of PD - this disease has robbed all of us in so many ways. Strength, gait and balance, coordination, memory, exec function, etc.

Reversal is, in my opinion, an individual thing. Some of us will have the strength and will power to get back. A good night's sleep for a week straight would be great for many. A clear mind also has its reward. For me when all this started, was just to get down on the floor, and wrestle with my grandkids.

Keep moving. God Bless.

[Farooqji in reply to Isthistheone]

Are you taking Nilotinib with consent of your doctor or on your own? Do you measure and record symptoms to monitor the progression?

[Isthistheone]

My Neuro in Albany would not write a prescription for Tasigna off label for my PD. I located an out of state neurologist who wrote the prescription. I journal daily the time i dose with Tasigna and Sinemet and the total daily amount of L-dopa. I went several months without Tasigna as the prescription was only good for one year. My insurance company put up roadblock after roadblock when I tried to renew it.

I was without Tasigna for about six months. My L-dopa intake doubled from 1100 mg to 2200 mg. I feel pretty confident with time I'll be able to get. . Look at my previous posts for the positive results I had back then. Hard to type now, going "off" meds.

[felixned]

Hi iqbaliqbal, i think that the file you originally had for download had description or summary of sorts. In it there was brief description of the test development for lrrk2 kinase activity level. This test to be used in clinical settings. Could you post this paragraph please?