CDNF, Potential DMT for Parkinson’s, May Work as Nasal Spray

A potential Parkinson’s therapy based on a protein with an ability to protect neurons — called recombinant (lab-made) human cerebral dopamine neurotrophic factor (rhCDNF) — has been transformed into tiny nanoparticles that may allow for its use as a nasal spray, Herantis Pharma, its developer, announced.

Nanoforming, the process of engineering rhCDNF (also known as CDNF) into nanoparticles, those thousands of times thinner than a human hair, was conducted by Nanoform using its nanoparticle technology.

Under a February partnership agreement, Nanoform conducted proof-of-concept studies to determine if its nanoforming process could be applied to rhCDNF, making it suitable for intranasal spray delivery. Currently the treatment, which aims to stop Parkinson’s progression, needs to be administered directly into the brain using an implanted delivery system suited for Parkinson’s patients.

Results showed that rhCDNF was successfully engineered into nanoparticles. Most importantly, the treatment retained its protein structure, essential for it work as intended. Further tests supported that rhCDNF, as nanoparticles, maintained its effectiveness and neuroprotective effects.

“This was a key milestone to achieve as part of our broader intranasal administration project for rhCDNF, one of only a few clinical stage assets focused on disease modification of Parkinson’s disease,” said Craig Cook, CEO of Herantis Pharma.

“The ability to nanoform the rhCDNF molecule improves the chances of success for intranasal administration and creates additional possibilities to impact the lives of patients. We very much look forward to progressing the work with Nanoform,” Cook added.

Another study will now further refine the size and shape of the rhCDNF nanoparticles, and evaluate their distribution when delivered as minimally invasive intranasal spray.

“We look forward to now moving into … further nanoforming activities as rhCDNF continues its development,” said Christian Jones, chief commercial officer of Nanoform.

Parkinson’s is characterized by the loss of nerve cells that make the neurotransmitter dopamine, a chemical messenger that allows nerve cells to communicate and, among other functions, helps regulate movement.

CDNF, found naturally in blood and the cerebrospinal fluid (the fluid bathing the brain and spinal cord), is a neurotrophic factor, or a protein that helps nerve cells survive. In studies involving animal models of Parkinson’s, CDNF protected and regenerated nerve cells.

Preclinical work also showed CDNF could repair nerve cells and induce dopamine production. Its use also lessened alpha-synuclein accumulation — another Parkinson’s hallmark — and nerve cell inflammation.

A Phase 1/2 clinical trial (NCT03295786) tested CDNF’s safety and tolerability in 17 patients with advanced Parkinson’s disease; each had five to 15 years of evident motor symptoms.

In a first part, patients at sites in Finland and Sweden were randomly assigned to monthly infusions of a medium or high dose of CDNF, or to a placebo for six months. This was followed by a six-month extension period, in which all were treated with CDNF each month, including those previously on placebo.

CDNF was administered directly into patients’ brains through a delivery system implanted by a neurosurgeon.

Top-line data showed that CDNF was safe and well-tolerated in both the trial’s first randomized and second open-label phase. No dose limiting toxicities were evident.

Treatment at the one-year mark also eased motor symptoms and showed a potential to slow disease progression in some patients. Positron-emission tomography (PET) imaging scans of brain areas where CDNF was administered registered higher levels of dopamine transporter, a protein that regulates the flow of dopamine between neurons.

Alternative delivery methods are needed because via a direct-to-brain implant, CDNF’s administration is not suitable for people with early stage Parkinson’s, “the optimal patient population for a neurorestorative treatment aiming to rejuvenate the remaining dopamine neurons,” Herantis reported on a webpage.

parkinsonsnewstoday.com/202...

[WinnieThePoo]

Thank you. Excellent post. Remind me why I'm on this forum. I'd been starting to wonder recently

[JohnPepper]

Beware of any claim which says"may". It does not say "Does". If it did, they woiuld tell you. It is justv one more product to mislead the patient.

[Dap1948 in reply to JohnPepper]

Oh allow people some hope John!

[JohnPepper in reply to Dap1948]

Selling expensive drugs in the HOPE that they MAY make you better, is misleeding an leads people to LOSE HOPE!

Daphne, you exercise and keep fit and have not changed since the day I first saw you. THAT BRINGS HOPE to othjers, but of course, they have to do the exercise!

REAL HOPE comes when we are able to see the results of exerting ourselves, when we know we are getting better, but OH! what a price to have to pay to get that hope. It seems too much for some, but if only they tried!

[Dap1948 in reply to JohnPepper]

I don’t think they’re selling them yet, just investigating and trialling. Yes things (exercise, B1 and more) have worked for me. I’m very lucky. But I also have friends who have worked hard at the walking, just as you prescribe, yet their Parkinson’s has progressed. There are also people who can’t exercise for whatever reason. They need hope.

[Despe in reply to Dap1948]

". . .just investigating and trialling. "

That is all I have been reading since I joined this forum! Guess that's hope, too. . .

[JohnPepper in reply to Dap1948]

My experience tells me that thiose who have tried and failed are thise whi did not stick to the rules - Start at no more than 15 minutes, walk every 2nd day, increase time by no more than 5 minutes after every 2nd week and never walk fast for more than an hour.

The other common problem is they don't walk as fast as they possibly can! How woulfd they know that? If they can say more than 3 words while walking fast then they are not walking at theiir maximum speed. If they cannot speak at all, they are going too fast.

These are all simple rules but so many people think that they can do more, therefor it is better, WRONG! Others are conrent to amble along at what they THINK IS FAST but is not!

If these people are doing everything properly I would like them to contact me .

[WinnieThePoo in reply to JohnPepper]

No John. Its just at an early stage of development. So far tests are promising. If they go well, and somebody actually starts selling something, then they may well say does.

But for now they have made a worthwhile development and are keeping people informed

But nobody is selling anything at the moment

[JohnPepper in reply to WinnieThePoo]

Surely controlled studies can be done to prove or disprove their claims! Six months should produce results or even three would give an indication that a reversal or even a halting of progression has happened. It is much cheaper to get patients to use it, while they make money from it!

[WinnieThePoo in reply to JohnPepper]

I think you are once again demonstrating how little you understand

[JohnPepper in reply to WinnieThePoo]

I obviously don't knpw anything about controlled stdies, how could I? It is the proincipal of deciding to carry out a stdy that I am talking about.

[WinnieThePoo in reply to JohnPepper]

"It is much cheaper to get patients to use it, while they make money from it!"

Lets start simple. I have quoted you above.

Explain to me please how drug companies make money from carrying out trials

[JohnPepper in reply to WinnieThePoo]

Drug companies woiuld only carry out trials on things THEY THINK will work. If tjhe trial is successful then they make money. If they think something will not work then they drop it.

[eschneid]

Thanks, made me a bit hopeful reading your post and while it mentions animal models, mice aren't specifically mentioned. I am fed up with cured mice....

[WinnieThePoo in reply to eschneid]

The CDNF has had a successful, if limited human trial by direct application in the brain using a neurosurgical implant. So definitely not only mice. Hopefully it will be possible to use a nasal spray instead

[eschneid in reply to WinnieThePoo]

Thanks Poo.......Nasal spray is interesting. Speed is not on our side with all these clinicals as us more advanced PDers may not benefit much from progression slowing devices..........CARPE DIEM!!!

[JohnPepper in reply to WinnieThePoo]

Why insert GDNF when all we have to do is encourage the body to produce more?

[WinnieThePoo in reply to JohnPepper]

Can you provide me with a link to any scientific evidence that exercise produces GDNF in the brain, or is capable of crossing the blood brain barrier? You have 60 years experience, have published a book, and run a web site, and regularly ask such questions - so I assume you have some scientific basis for your ideas.

Or did you just make them up because you have no idea what you are talking about?

Don't bother with answering the last question - just supply evidence in support of your claim, if you can

[JohnPepper in reply to WinnieThePoo]

GDNF cannot cross the BBB. If it could, our problems woiuld be solved. I have said that I know of no evidence of the brain being able to produce more GDNF. I would think that is more to do with the business efficacy of proving the brain produces more GDNF if we do exercise, would be shooting themselves in the foot.

I have deduced that my brain produces more GDNF because it is the only logical reasonm why I have got better. IT is also the most logical reason why I get worse when I stop the walking.

That conclusion is backed up by the medical world's hesitancy to talk about GDNF. It seem to be a taboo subject. All they say about GDNF is that it does not cross the BBB therefore it is not worth discussing!

[WinnieThePoo in reply to JohnPepper]

John that's nonsense and I think you know it is

[JohnPepper in reply to JohnPepper]

What part of what I said is Nonsense? Is it my claim that my brain produces more GDNF by doing fast walking? Or is it my GUESS that the nedicakl world does not want people to know too much about GDNF?

I have been to Pd conferences in the USA and here in SA, and when I have asked the speakers about GDNF, they have all given the same answer - 'GDNF does not cross the BBB!' But in each case I had already first told them about my experience but they totally ignored what I said. What conclusiuon would you draw?

[Hidden in reply to WinnieThePoo]

Can you provide a link to any scientific evidence that exercise such as fast walking does not produce GDNF in the brain?

[WinnieThePoo in reply to Hidden]

Nor can I provide proof that santa-claus doesn't exist. Grow up

[Hidden in reply to WinnieThePoo]

Then your theories are unsupported by evidence. According to what you just said to John an hour ago, it looks like you believe theories unsupported by evidence are nonsense. I therefore present to you that your theory (that GDNF cannot be produced in the brain by exercise such as fast walking) is nonsense.

[Hidden in reply to WinnieThePoo]

My point is: If no studies exist, then both sides are only left with opinions. I don't actually think your theory is nonsense.

What I would really like to see here is the ability for everyone to post in peace, even if their approach is not mainstream.

[WinnieThePoo in reply to Hidden]

What I would like is if people stopped pseuding up mystical protocols like a fairground fortune teller. What exactly does the gdnf theory bring to the party? Apart from pseudy mysticism what does it matter whether exercise is good for the brain just cos it is? Why bring gdnf into the discussion?John has no idea what it is beyond a magic fairy goo that mends neurons he read about somewhere 40 years ago, but then uses the fact that scientists can't do Harry Potter magic to dream up conspiracy theories that "They" are deliberately not curing parkinson's out of spite and to make profits. And ignores the sdfact that he doesn't have PD himself and his ideas don't work for people who do have PD**, to give false hope and potentially dangerous advice regarding medication.

**benefitting from symptomatic relief from starting exercise is a fine thing which is universally recognised, but it's not the same as his claim to reverse the disease and halt progression

[Hidden in reply to WinnieThePoo]

I don't think the answer is to censor those opinions that we do not like.

It can be hard to go against firmly established beliefs (case in point: "I think the world is round!"). That does not mean the new idea is without merit; it does not mean the new idea is incorrect or untrue.

What do insults and ridicule bring to the picture? (this is a sincere question; I'm wondering why you keep doing this)

[Zella23 in reply to WinnieThePoo]

My husband and I watched this programme about delivering the cdnf directly to the brain and the positive results it made to many PD patients. It definitely improved many of the participants life and the drug company that had been sponsoring decided not to go any further. We felt very disappointed it was going to be discontinued, although the delivery system of the drug directly into the brain was invasive.If the above company can produce a nasal delivery system it sounds extremely promising as you say.

journals.sagepub.com/doi/10...

Interesting article here explaining differences between GDNF used in the Bristol trial and CDNF used in the nasal spray.

[WinnieThePoo in reply to Zella23]

The documentary was about GDNF, not CDNF. It was a trial run by Bristol University, not a drug company, although Pfizer sponsored it (and withdrew their sponsorship)

This is a different molecule and a Finnish pharmaceutical company

[Zella23 in reply to WinnieThePoo]

Yes just edited my response and found some research showing the difference between the two. Thanks for responding.

[Discogs_discogs]

It could be a very long time before this nasal spray exists commercially and, in fact, it might never hit the market for sale to the public -- even if it is an effective remedy.

[eschneid in reply to Discogs_discogs]

Thanks for the optimistic outlook!!

[Discogs_discogs in reply to eschneid]

Sorry, let me rephrase that: I hope this becomes a commercial viable product so that the pharmaceutical industry will pursue it for the benefit of all persons with PD.

[WinnieThePoo in reply to Discogs_discogs]

The pharmaceutical company which has developed and patented rh-cdnf is Herantis pharmaceutical, a Finnish company. They stand to earn substantialy more from the molecule if they can supply it as a nasal spray. It t won't be marketed tomorrow, but the clock is ticking on Herantis patent so they won't be dragging their feet

[eschneid in reply to WinnieThePoo]

Thanks Poo for adding some useful info to the post about Herantis and not just a general opinion that all these hopeful PD clinicals/products take way too long and most hit a wall somewhere along the line.

[Skidad]

My first post. Overall, the article gives me hope. However, the part about nasal spray made me wonder: did my seasonal use of a steroid nasal spray for sinus allergy "cause" my PD? I suppose the contents of a non-prescription spray are not "nanoform". So the active ingredients probably did not penetrate the blood-brain barrier, and my use of this product is not what induced PD.

[JohnPepper]

Again! We have the word, "May" in connection with a nasal spray. As a natural chemical, sufrely the best way to mapproach the problem is to find out what produces it and then finfd out how to encourage the body to produvce more.

The answer to that question, the same as for GDNF is, "What ggo would that do for Big Pharma?" Nothing! So it is dead in the water.

I am quite certain that my body is prducing more GDNF or maybe even CDNF, because it is the only way I could have reversed mt symptoms. It is not a cure, but as long as I do the walking , my symptoms stay at a low level, but when I stop, they slowly return! But thta does nothing for the medical world, it only helps the patients!