Earlier this week, Ladenburg Thalmann, a US investment firm hosted a Healthcare Symposia. One of its guest speakers was Dr. Charalampos (Haris) Tzoulis, Professor of Neurology and Neurodegeneration at the University of Bergen and Haukeland University Hospital, Bergen Norway. Dr. Tzoulis recently completed a Phase 1 clinical trial testing vitamin supplement Nicotinamide Riboside “NR” (FAQs) (Anecdotes) in Parkinson’s patients. Here’s how Dr. Tzoulis explained why he initiated the study:

At 16:30 of Dr. Tzoulis’ Presentation (link to presentation at bottom):

“It has indeed been shown in cell models and a number of animal studies that increasing NAD levels in the body, in the cells in general, seems to be beneficial against a number of different conditions ranging from obesity to heart failure, kidney disease, myopathies, diseases affecting the sensory organs — the eye and the ear, and last but not least, neurodegeneration.

And, of course, even I, when I first came into this NAD field, I thought it was awkward that a single treatment or a single intervention would essentially affect all these different diseases having completely different molecular mechanisms.

But, indeed, I think what’s happening here is that by increasing NAD levels in the cells, we are increasing — in addition to attacking specific disease processes — we are increasing cellular resilience by optimizing cell metabolism.

And we will look a little bit more about these things, and I’ll give you a little bit more results and findings supporting these claims.

So, interesting for neurodegeneration is that NAD levels have been shown to decline with age.

And this is something that has been shown primarily in blood and peripheral tissues.

But, now, evidence is being published gradually that perhaps also in the human brain, we have declining NAD levels with age.

And the reason why NAD levels decline has not yet been determined.

But, we know that one of the mechanisms responsible is an increased consumption of NAD.

So, not only a decreased production, but also an increased consumption due to processes such as DNA repair which are very expensive in terms of NAD — which require NAD in order to function.

So, why is this interesting for neurodegeneration?

Obviously, because age is the single strongest known risk factor for neurodegenerative diseases.

So, not only that, but specifically in Parkinson’s disease, there is evidence linking the pathogenesis of this disorder to aberrant NAD metabolism.

This is where a lot of the research of my lab has been focused for the last 10 years.

So, we and others have shown that in the brain, in neurons with people with Parkinson’s disease, there is evidence of significant failure or disfunction of the mitochondria — the powerhouses of the cell.

And we’ve been able to link this to aberrant NAD metabolism because mitochondria and the process of cellular respiration is central, a process intimately linked to NAD metabolism.

But we were also able to show evidence of the consequences of aberrant NAD metabolism, in this case, in the form of aberrant regulation of gene expression, an increased circulation of histones in the human brain — something that is normally regulated by the levels of NAD.

And when NAD is deficient or in insufficient amounts, this is exactly what will happen: Protein aceytlation including histone acytelation will not be regulated any more. And this will result in aberrant regulation of our gene expression.

At the 19:58 mark — The Case for NAD Precursors:

“So, it seems that NAD metabolism is linked to the process of aging. It is something that’s declining or failing with aging.

And this seems to be even more so in the case of neurodegenerative diseases like Parkinson’s.

So, based on this, we felt that there was a strong rationale to try and replenish NAD or increase NAD levels as a treatment strategy for patients.

And, when one wants to increase NAD, it is common to do it via the use of precursors because NAD itself is not a very stable molecule so that we could give it directly to the patients.

So, it is common to employ different precursors that are substances once inside the body will be converted to NAD.

At the 20:45 mark — Why His Team Chose NR:

“There’s a number of different NAD precursors.

We chose to go with Nicotinamide Riboside or NR for many reasons.

One of the reasons was that NR was certainly the most well studied of the NAD precursors — and this is very important when we’re going to do human studies.

And it had repeatedly been proven to be safe both in a preclinical and a clinical setting.

The other advantage is that compared to Nicotinic acid or Niacin, NR doesn’t give any side effects. 

Niacin is also safe — but is associated with very bothersome hot flashing and redness of the skin.

So, there are many reasons to go with NR.

And we chose as NR as our supplement of choice in this case.

At the 29:25 mark — Comments on the Phase 1 Trial:

“Oral NR administration, 1000mg, 500mg twice a day, was associated with increased brain NAD levels in Parkinson’s disease. And, this, in turn, was linked to an improvement of the Parkinson’s disease metabolic pattern, measured by FDG-PET, and a mild but significant symptomatic amelioration of our patients.

At the 32 minute mark — Comments on the Phase 1 Trial:

“…Although the trial is small, and we don’t know whether or not it can delay the progression of Parkinson’s disease yet, it does show that it’s promising.

It does nominate NR as a potential neuroprotective therapy for Parkinson’s disease and potentially other neurodegenerative diseases, which merits further investigation.

At the 33:45 mark — Comments on the Phase 2 Trial:

So, inspired and motivated by these results, we moved onto a proper Phase 2 study — a large clinical trial aiming to determine whether indeed NAD replenishment by means of oral Nicotinamide Riboside (NR) can delay the progression of Parkinson’s disease.

The question we’re asking here is: Do we have the holy grail in our hands? Are we able to exert a neuroprotective effect or not? And this is what the study is going to output.

This is a large trial. We will recruit a total of 400 patients with Parkinson’s disease from all of Norway.

There are 13 centers currently enrolled in the study.

It’s a multi center study.

It’s, of course, double blinded, randomized, and the patients will be randomized to either placebo or 1000mg, 500mg twice a day of Nicotinamide Riboside “NR” for a total duration of 1 year or 52 weeks.

They will be followed with a number of visits, and a number of different scoring tools both clinical and also imaging, as well as biochemical and metabolic measures.

The study is ongoing. We had a meeting today where I was informed that we have now recruited approximately 260 patients in this study

So, it’s going well.

We anticipate it will be concluded at the end of 2024.

So, another 2 years.

And then we’ll have an answer to this question.

RELATED:

  • You can watch the full presentation HERE
  • New Phase 1 Clinical Trial Results Show Nicotinamide Riboside (NR) as a Potential Neuroprotective Therapy for Parkinson`s Disease. Why is This Important? (Link)
  • NAD and Parkinson’s Disease – The Clinical Studies (Science of NAD)
  • FAQs on the Potential for Nicotinamide Riboside (NR) in Alzheimer’s Patients (Link)

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