Prognostic studies in the context of Alzheimer's disease (AD) mainly predicted time to dementia. However, it is questionable whether onset of dementia is the most relevant outcome along the AD disease trajectory from the perspective of patients and their care partners. Therefore, the authors aimed to identify the most relevant outcomes from the viewpoint of patients and care partners.

They used a two-step, mixed-methods approach. As a first step they conducted four focus groups in the Netherlands to elicit a comprehensive list of outcomes considered important by patients (n = 12) and care partners (n = 14) in the prognosis of AD. The focus groups resulted in a list of 59 items, divided into five categories.

Next, in an online European survey, they asked participants (n = 232; 99 patients, 133 care partners) to rate the importance of all 59 items (5-point Likert scale). As participants were likely to rate a large number of outcomes as "important" (4) or "very important" (5), the scientists subsequently asked them to select the three items they considered most important.

The top-10 lists of items most frequently mentioned as "most important" by patients and care partners were merged into one core outcome list, comprising 13 items. Both patients and care partners selected outcomes from the category "cognition" most often, followed by items in the categories "functioning and dependency" and "physical health." No items from the category "behavior and neuropsychiatry" and "social environment" ended up in the core list of relevant outcomes.

Conclusion: The authors identified a core list of outcomes relevant to patients and care partner, and found that prognostic information related to cognitive decline, dependency, and physical health are considered most relevant by both patients and their care partners

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This paper aim at the analysis of the role of the circadian regulation of ghrelin levels in patients with Parkinson's disease.

Based on the literature data, patients with Parkinson's disease have clinical fluctuations in the symptoms of the disease, manifested by the diurnal changes in motor activity, autonomic functions, sleep-wake cycle, visual function, and the efficacy of dopaminergic therapy.

Biological rhythms are controlled by central and peripheral oscillators which links with dopaminergic neurotransmission - core of the pathogenesis of Parkinson's disease. Circadian system is altered in Parkinson's disease due to that ghrelin fluctuations may be changed.

Ghrelin is potential food-entrainable oscillator because it is linked with clock genes expression.

In Parkinson`s disease this hormone may induce eating behavior changing and as a result metabolic disorder.

The "hunger hormone" ghrelin can be a biomarker of the Parkinson's disease, and the study of its role in the pathogenesis, as well as its dependence on the period of the day, intake of levodopa medications to improve the effectiveness of treatment is promising.

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A randomized, placebo-controlled phase III study (AB10015) which ended in 2018 that orally administered masitinib (4.5 mg/kg/day) slowed rate of functional decline, with acceptable safety, in amyotrophic lateral sclerosis (ALS) patients having an ALS Functional Rating Scale-revised (ALSFRS-R) progression rate from disease onset to baseline of <1.1 points/month. As the 2018 study lasted roughly 3 years and a few months, this is not enough to create survival analysis. As patients were invited in a subsequent open label program, some information is known how they behaved during more than 6 years. This open label is under control of a local physician and dosing decisions are made solely by them.

In this article two employees of AB science, plus other contributeurs like the great ALS scientist Albert Ludolph reanalyzed the results from this 2018 trial. All investigational sites from study AB10015 were contacted with a request for an update on each patient’s vital (survival) status. From the 384 patients in the initial study, only 84 were available for the analysis.

The authors selected groups of patients between the patients that participated to this trial based on their survival. Some patients were eliminated from this new analysis, because they were too ill during the study.

Three enriched subgroups were defined: * patients with loss of ALSFR-R  < 1.1 regardless of their baseline ALSFRS-R score; * patients with ALSFRS-R ⩾2 on each baseline ALSFRS-R item, regardless of baseline ΔFS; * patients with ALSFRS-R ⩾2 on each baseline ALSFRS-R item and ΔFS < 1.1

What the authors found was that there was no real difference between patients who took masitinib 4.5 mg/kg/day versus the placebo group. So this what was found initially.

Yet when they compare a subgroup with the placebo they find a real difference. This subgroup is comprised of ALS patients that have not suffered a complete loss or severe impairment at the time of masitinib treatment initiation and have not experienced a rapid (ΔFS ⩾ 1.1) progression rate from disease onset to baseline.

In summary the authors selected a subgroup of patients (on their ALSFRS-R status) that did well and not surprisingly, they found these patients did well compared to the placebo.

So they conclude by this astonishing statement: A significant survival benefit of 25 months and 47% reduced risk of death (p = 0.025) was observed for patients receiving 4.5 mg/kg/day masitinib (n = 45) versus placebo (n = 62)

In an ideal world, scientists do not do that kind of analysis. Yet these reanalyzed studies have already been done; for example, the edaravone, rasagiline and high-fat intervention clinical trials.

There are many questions that could be asked about this study, in particular how could the small subsets of patients in sub-groups could statistically reflects the four times larger number of patients in the clinical study.

There is a lot of pressure on Biotechs, they are unfunded, actually most of them are on verge of bankrupt and the only way they could become profitable is if a big company buy them. There is also a lot hypocrisy on the part of large corporations as they do not do research on rare diseases (even Biogen works with Ionis). Instead as fat cats they wait for a succeeding trial to buy the biotech. So hundred biotech fail before one could be bought, this is an incredibly inefficient way to find new drugs.

So the reader of this blog is invited to take any enthusiastic statement by a biotech with a grain of salt.

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