Phase 4 study to evaluate efficacy of orally administrated Trehalose in individuals with idiopathic & LRRK2-associated Parkinsons

New clinical trial registered:

NeuromedIRCCS researchers have registered a small (N=20) open label Phase 4 study to evaluate efficacy of orally administrated Trehalose in individuals with idiopathic & LRRK2-associated #Parkinsons

twitter.com/ScienceofPD/sta...

clinicaltrials.gov/ct2/show...

[Hidden]

“Enrolled subjects will daily take 4 g of trehalose in oral administration for 24 weeks.”

I wonder the approx volume of 4 grams.

Is there any way of knowing if it is once a day or spread out?

[park_bear in reply to Hidden]

For the trehalose in my possession four grams amounts to one level teaspoon.

[Hidden in reply to park_bear]

When Trehalose was last discussed I believe based on mouse data you concluded more than 4 grams would be needed. Do you recall what weight you arrived at? 4 grams seems low. I have been using 1 -2 teaspoons for most of a year.

[park_bear in reply to Hidden]

I agree that four grams does seem low. Based on an effective dose in monkeys the human equivalent dose to that was .9 grams per kilogram, which would amount to a couple of ounces for a 60 kilogram person, which seems like a lot. Less might do but this is unknown.

[Hidden in reply to park_bear]

Why would they focus on LRRK2 when Trehalose method of action they are pursuing is autophagy and reduced autophagy is a defining characteristic of PD and aging in general? If it benefits LRRK2, wouldn’t it benefit idiopathic? Odd

Regarding volume to take, perplexing.

Also, they are aiming for inducing autophagy but as previously discussed / linked to, the autophagy induced via Trehalose might be indirect by means of altering the gut biome. Maybe that could explain why a low dose might work.

I’m inclined to stick with it just in case it works but as with most overything, I’m hopeful but not very optimistic

[park_bear in reply to Hidden]

Personally I am optimistic. There is extensive animal evidence showing trehalose efficacy with the LRRK2 mutation so I cannot blame them for focusing on that. This may affect you personally since you may have inherited this mutation. On the other hand here is some evidence showing trehalose is generally effective in reducing uptake of extracellular aSyn:

nature.com/articles/s41598-...

[H4 cells do not produce much aSyn on their own]

"We treated H4 cells with trehalose prior to aSyn exposure and observed that trehalose diminished the formation of large LysoT+ clumps (Fig. 9a,b), when compared to cells exposed to aSyn only. This effect was particularly significant in cells exposed to fibrils. As an accumulation of exogenous aSyn in fibril-exposed cells was readily detectable by ICC, we used this species for evaluating the effect of trehalose on the accumulation of exogenous aSyn. We observed that trehalose pretreatment reduces the accumulation of aSyn in exposed H4 cells (Fig. 9e), by determining either aSyn counts/cell or the counts of larger aSyn aggregates. "

"Importantly, the positive effects of trehalose in the reduction of dilated lysosomes and accumulation of exogenous aSyn, especially in the formation of larger aSyn aggregates, were also observed in primary neurons(Fig. 9c,d,f). Taken together, the findings from both H4 cells and primary neurons substantiate the protective effects of trehalose on aSyn mediated-impairment of lysosomes and on the clearance of accumulated exogenous aSyn in the recipient cell"

They did use a really high concentration of trehalose though, 100mM trehalose, which compromises the validity of this work.

[Hidden in reply to park_bear]

Thank you My capacity for optimism is diminished due to frustration.

Are you familiar with heat shock proteins?

I can post info if if you are interested.

I believe that is truly a definite and I have never referred to anything other than exercise and sleep as a definite.

Also, glymphatic drainage via lymphatic drainage is looking very interesting

[park_bear in reply to Hidden]

Thanks, but already info saturated for the day.

[Hidden in reply to park_bear]

Me too. I just wanted to reciprocate. Have a good weekend PB

[park_bear]

Brief Summary:

" LRRK2 G2019S mutation is one of the most common causes of familial PD. The phenotype corresponding to this mutation is a late-onset form of PD characterized by the accumulation of the N-ethylmaleimide sensitive factor (NSF) in neurons. It is due to a dysfunction of the physiological autophagy processes occurring at cellular level, mainly affecting autophagy mediated by chaperone proteins (Chaperon Mediated Autophagy, CMA), responsible for the clearance of alpha synuclein at the lysosomal level. This condition, although sensitive to treatment with L-DOPA and dopamine agonists, does not currently have any specific therapy.

Recently, in a mouse model carrying the LRRK2 mutation, it has been demonstrated that treatment with trehalose is able to reduce the accumulation of NSF deposits in neurons of various brain areas such as the substantia nigra, striatum, cortex and hippocampus. The reduction of protein aggregates correlates with intracellular molecules related to the activation of apoptotic processes in damaged neurons. Moreover, it has been found a significant improvement in motor and cognitive performance."

[Hidden in reply to park_bear]

“ The median AAO was 60 years (interquartile range = 52-67.25) for tobacco users, compared to 52 years (interquartile range = 45.25-61) for non-users “ Median age of onset for non smokers with LRRK2 is 52.

Interesting Trehalose trial refers to that as late onset. Under 50 is YOPD so I guess there is no “middle onset”

pubmed.ncbi.nlm.nih.gov/328...

LRRK2 may reduce autophagy even more than idiopathic but it is my understanding that reduces autophagy occurs with age in all populations. I therefore wonder if Trehalose could be beneficial to all PWP regardless of genetics.

[gregorio]

I have just become used to taking Manitol.. is there a difference

[CardiCorgi]

I foresee this as not working. I can not imagine 4 g per day having any meaningful impact, but I'm not a researcher so I will eagerly await the results. -

For the record I upped my intake to 75 g per day (about 3 heaping Tbs in a cup of coffee - 4 calories per gram or 300 calories), BUT . . . and this is a big but for me . . . I believe whole heartedly that it is the combination of my total routine that is making a difference. I am a vegan, exercise at least 3 times a weeks including 30 minutes on a treadmill (although I've slowed down considerably), stretch or do yoga, and take a LONG list of daily supplements. Recently I've become a big believer in the power of creatine to help keep my muscles from declining. It is the only supplement I have ever taken where I could actually feel a meaningful physical difference after a week.

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For those who don't know me or my posts I do not have Parkinson's but rather an illness known as SCA1, but the root cause of my disorder is a mutant protein that causes damage to cells in the brain, and so I started posting on the Parkinson's forum because I felt what I was doing might be helpful to some Parkinson's patients as well since some forms of Parkinson's clearly stem from damage caused by the oligomerization of alph-synuclein.

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Also for the record I continue to have a full blood panel done every 6 months and nothing adverse as of yet has shown up, but I am now going on 6 years with little or no disease progression and maintain my position as a B777 Captain whilst others with my exact same diagnosis and at my exact same age (56) are using a walker or even a wheelchair.

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Here is a link to my full routine:

longecity.org/forum/topic/1...

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I understand the research on trehalose points to limited potential if any when taken orally, but given the risk reward ratio and the fact it is a simple sugar substitute used in hundreds if not thousands of food products, I can not imagine why anyone with a known neurological disorder like Parkinson's or Huntington's or SCA wouldn't be taking it daily.