Fritz Wörwag Research Prize: New Findings on Neuroprotective Effects of Biofactors

On the occasion of the congress of the German Diabetes Society 2018, the Fritz Wörwag Research Prize was awarded on May 9 for new findings on biofactors – this year on the topic of "Biofactors for Neuroprotection".

For his work on the influence of genetic variations in the glucose metabolism on the characteristics of diabetic neuropathy, Prof. Dan Ziegler from the Institute of Clinical Diabetology at the German Diabetes Centre at Heinrich Heine University in Düsseldorf received the first prize of €10,000. The second prize in the amount of €8,000 went to Prof. Jacqueline A. Pettersen from the University of Northern British Columbia in Prince George, Canada, for the results of her research into vitamin D and cognition. 

The work of Ziegler et al. was evaluated by the independent jury as a "revolutionary approach in the analysis of factors that lead to the development of diabetic complications, in particular diabetic neuropathy." The findings could help explain why severe neuropathy occurs in some patients, while its progress is milder in others with comparable diabetes control and duration, according to the panel of scientists. Ziegler and his team investigated to what extent different gene variants (polymorphisms) of a key enzyme in the glucose metabolism influence the symptoms of diabetic polyneuropathy (1). In more than 500 type 1 or type 2 diabetes patients with a maximum diabetes duration of one year, they identified nine polymorphisms for the enzyme transketolase and correlated them with the clinical and neurophysiological characteristics of neuropathy. This brought to light specific relationships between individual gene variants and certain manifestations of neuropathy. 

Key enzyme for avoiding diabetes complications

Earlier studies had suggested that the activity of transketolase could have a decisive influence on the development of microvascular secondary diseases: the enzyme channels intermediate products of glycolysis which accumulate as a result of hyperglycaemia into an alternative degradation pathway. This inhibits pathological degradation processes in which the accumulated metabolites are otherwise converted into substances that damage the vessels. 

A clinically relevant relationship with the biofactors results from the fact that the transketolase requires vitamin B1 (thiamine) as a cofactor; its activity is therefore also dependent on the supply of the vitamin. However, patients with diabetes often have thiamine deficiency due to increased renal excretion (2). Previous studies by international research teams had shown that the thiamine precursor benfotiamine can increase transketolase activity and thereby inhibit processes that damage nerves (3,4). Neuropathic symptoms can be alleviated by treatment with benfotiamine (5,6). Ziegler's investigations now confirm that there is a connection between transketolase and the clinical manifestations of neuropathy. Pharmacogenomic knowledge about transketolase polymorphisms could contribute towards optimising these treatments in the future, Ziegler concludes.

High-dose vitamin D supplementation improves visual memory

The winner of the second prize, Prof. Jacqueline Pettersen, focused on another important area of neuroprotection: in a randomised study of 82 healthy adults, the Canadian scientist investigated the effect of low-dose vitamin D supplementation (400 IU per day) on cognitive performance compared to high-dose administration (4,000 IU per day) over 18 weeks (7). It was found that non-verbal (visual) memory was improved by the higher-dose supplementation, especially among the participants with insufficient vitamin D levels (< 75 nmol/l) at the beginning of the study. In contrast, no differences in verbal memory or other cognitive performance were observed. Pettersen concludes from the findings that vitamin D is important for demanding cognitive functions, especially for the nonverbal (visual) memory, which also utilizes executive functioning processes.

In the jury's opinion, with her study the scientist highlights "a perspectively very important aspect for the prophylactic or therapeutic administration of a biofactor in view of the increasing problem of dementia.” The jurors also praised the very carefully conducted clinical trial.

This year the Fritz Wörwag Research Prize was awarded for the 9th time by the medium-sized family-owned business Wörwag Pharma from Böblingen. The aim of the science prize initiated by company founder Dr. Fritz Wörwag is to support and promote researchers in the field of the clinical application of biofactors. Biofactors include vitamins, minerals, trace elements and vitamin-like substances which can compensate for deficiency symptoms in physiological concentrations and have pharmacological effects at higher concentrations.

Sources:

1. Ziegler D et al. Association of transketolase polymorphisms with measures of polyneuropathy in patients with recently diagnosed diabetes. Diabetes Metab Res Rev 2017; 33: e2811

2. Thornalley PJ et al. High prevalence of low plasma thiamine concentration in diabetes linked to a marker of vascular disease. Diabetologia 2007; 50: 2164-2170 

3. Hammes HP, Du X, Edelstein D, et al. Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy. Nat Med 2003; 9: 294-299.

4. Du X, Edelstein D, Brownlee M. Oral benfotiamine plus alpha-lipoic acid normalises complication-causing pathways in type 1 diabetes. Diabetologia 2008; 51: 1930-1932.

5. Stracke H et al. Benfotiamine in diabetic polyneuropathy (BENDIP): Results of a randomised, double blind, placebo-controlled clinical study. Exp Clin Endocrinol Diab 2008; 116: 600-605 

6. Haupt E et al. Benfotiamine in the treatment of diabetic polyneuropathy - a three-week randomized, controlled pilot study (BEDIP Study). Int J Clin Pharmacol Ther 2005; 43: 71-77

7. Pettersen JA. Does high dose vitamin D supplementation enhance cognition? A randomized trial in healthy adults. Exp Gerontol 2017: 90; 90–97

Fritz Wörwag Research Prize
F.l.t.r.: Dr. Fritz Wörwag, Prof. Jacqueline Pettersen, Prof. Karlheinz Reiners, Prof. Dan Ziegler, Dr. Marcus Wörwag
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