Cerebrolysin® the latest approach to Alzheimer’s disease

By Phil Micans, MS, PharmB

It is well known that the debilitating disease of Alzheimer’s (AD) is a condition whereby patients have low levels of the brain neurotransmitter Acetylcholine (Ach) – at least as when compared to their healthy counterparts. Thus the “mainstream” approach to treat Alzheimer’s disease to-date has been to inhibit an enzyme from acting on Acetylcholine (Ach) and therefore from breaking it down, thus allowing more Acetylcholine (Ach) to be made available. This enzyme is called Acetylcholine (Ach) esterase and the prime Acetylcholine (Ach) esterase inhibitor prescribed today is donepezil (brand name Aricept®).

There is one exception; the drug memantine, (brand names Ebixa® and Namenda®). In this case memantine blocks the actions of excitotoxins in the brain and by so-doing has highlighted the fact that excitoxins themselves may play a role in the development of Alzheimer’s disease. As excitotoxins can be triggered by items found in the diet, particularly flavor enhancers such as MSG or sugar substitutes such as aspartate- this has highlighted the need to avoid and protect against these chemicals during our lifespans. (For an excellent detailed article on the role of excitotoxins in AD and aging, I refer you to the late James South MA article; “excitotoxins, the ultimate brain slayer” available at: www.antiaging-systems.com/extract/excitotoxins.htm ).

Before continuing, I would also like to mention Centrophenoxine and whilst it isn't approved, (e.g. recognised by a government for the treatment of Alzheimer’s disease), that a great authority on the subject- Professor Imre Zs.-Nagy, has highlighted that it can help to prevent and slow Alzheimer’s disease itself through its own unique actions.

Alzheimer’s disease

What is apparent is that something certainly needs to be done, for Alzheimer’s disease is now afflicting one in five persons over the age of 60. Today it is estimated that 27 million people worldwide are diagnosed with it, (by which time it is normally quite severe). Furthermore, due to the increasing aging population this figure is expected to increase by a factor of four by 2050, unless of course something can be found beforehand!

Losing our mental facilities, agility and our control over our personal lives as well as the impact of the disease, both psychologically, emotionally and financially on our loved ones and society at large, is not something that any of us want to impart in our older age.

So it is interesting that there is now a new and approved approach to Alzheimer’s disease (AD) that has become available in some European countries; its name is Cerebrolysin®

Cerebrolysin®

A company called Ebewe in the Germanic country of Austria has developed and gained approval for their injectable product called Cerebrolysin® (CRB).

What makes Cerebrolysin® (CRB) interesting is that it is specifically aimed at delaying the progression of Alzheimer’s disease; this is unusual in-itself because the current approved medications, (donepezil and memantine) are merely targeted at improving the symptoms and some of the disease outcomes.

Cerebrolysin® (CRB) is also different because it can be considered to be the first natural approach to Alzheimer’s disease. Cerebrolysin® (CRB) is peptide based, being very careful obtained by standardised enzymatic processes from purified brain proteins and aminoacids (of porcine origin).

Cerebrolysin® (CRB) is designed to help support the function of neurons. This type of approach is known as neurotrophic and Cerebrolysin® (CRB) being a neurotrophic factor appears to help support and maintain a number of neurons including those of serotonin, choline (related to Acetylcholine) and noradrenaline origin.

Action

What this means, is that Cerebrolysin® (CRB) appears to be able to except a growth like factor on neurons, particularly those from the dorsal root ganglia. Plus, Cerebrolysin® (CRB) appears to affect synaptic responses in the hippocampus, the region of the brain believed responsible for the deposit of memories. In other words, Cerebrolysin® helps to maintain and support these vital repair processes in the brain.

In addition, Cerebrolysin® has been shown to decrease amyloid-beta production in the brain. These are the so-called Alzheimer plagues that are seen in the post mortem examinations of Alzheimer’s disease autopsies. As these plagues are strongly correlated with the damage of Alzheimer’s disease, their control or reduction may be viewed as a highly significant benefit.

Furthermore, there is even some evidence that Cerebrolysin® (CRB) can decrease the rate of apoptosis (the rate of cell death), a factor that could be linked to the slowing of the progression of the disease.

Clinical trials

Now that 80 trials have been completed on more than 5000 patients with Alzheimer’s disease, Cerebrolysin® (CRB) can be considered to be well tested.

The studies highlight that those patients suffering from mild to moderate Alzheimer’s disease, that when treated with I.M. or I.V. infusions of Cerebrolysin® (CRB) each day for 5 days a week, over a period of 4 weeks, that there was a significant improvement in cognitive measurements, even after just the first 4 initial weeks. What’s more, Dr. E. Ruether, one of the doctors involved in the trials, noted that these improvements remained stable for up to 6-months- even after cessation of the therapy.

In more human terms this means that there are improvements in the activities of daily living, with the patients being able to do more by themselves, with far less assistance etc. Furthermore, when compared to the placebo patients in the trials, the Cerebrolysin® (CRB) treated patients retained their improved cognitive measurements, even at month 7, whereas the placebo patients had clearly deteriorated during this same period.

Safety

To date, no known toxicity or safety concerns have been reported. Side effects during treatment have been rare and generally limited to dizziness, headache and heat sensations, although it is possible that these effects are related to the injection or I.V. being given “too quickly”.

Potential contraindications appear to be limited to individual hypersensitivity, severe renal conditions and epilepsy.

Dosage

The normal dose pattern appears to be a 5 ml ampoule injected, (intramuscularly or intravenously) each day for 5-days (e.g. Monday-Friday) and repeated for a period of 4-weeks. Then after a 2-month period free from treatment the program is cycled again as necessary. Therefore, four packages each containing 5x 5ml ampoules are normally enough for 3-months at a time.

Summary

Cerebrolysin® (CRB) is a unique departure for approved drugs for Alzheimer’s disease for the following reasons:
1. Firstly it is aimed at the prevention/ slowing the progression of the disease rather than alleviation of specific symptoms.
2. Secondly it does not merely improve Ach levels, but rather enhances overall neuronal condition.
3. Thirdly, it can be considered to be a more natural approach, because rather than the current drugs, it is formed from natural brain proteins.
4. It has far fewer side effects and contraindications than the existing therapies.
Overall, CRB has been shown to help modify the course of AD and delay its progression leading to a stabilising effect on Alzheimer’s disease patients.
All of this appears to have been achieved with very few side effects and contraindications which makes CRB a welcome addition to the armoury in the fight against the plague that is Alzheimer’s disease.

References

1. Rockenstein E, Torrance M, Mante M, Adame A, Paulino A, Rose JB, Crews L, Moessler H, Masliah E “Cerebrolysin decreases amyloid-beta production by regulating amyloid precursor maturation in a transgenic model of Alzheimer’s disease” J. Neurosci. Res. (2006) May 15;83 (7) 1252-61
2. Masliah E, Armasolo F, Veinbergs I, et al., “Cerebrolysin ameliorates performance deficits and neuronal damage in apolipoprotein E deficient mice.” Pharmacol. Biochem. Behav. (1999), 62 (2): 00 239-245
3. Jonhagen ME, “Nerve growth factor treatment in dementia” Alzheimer disease and associated disorders (2000), 14: S31-38
4. Ruether E, Ritter R, Apecehea M, et al. “Efficacy of the peptide nootropic drug Cerebrolysin in patients with senile dementia of the Alzheimer type,” Pharmacopsychiatry (1994), 27 (1), pp 32-40
5. Xiao S, Yan H, Yao P, “Efficacy of Cerebrolysin in patients with Alzheimer’s disease” Clin. Drug Invest (2000), 19 (1): pp 43-53
6. Ruether E, Ritter R, Apecehea M, et al. “Sustained improvement in patients with dementia of Alzheimer’s type 6-months after cessation of Cerebrolysin therapy” J. Neural. Trans. (2000), 107 pp 815-829
7. Bae CY, Cho CY, Cho K, et al. “A double blind, placebo controlled, multicenter study of Cerebrolysin for Alzheimer’s disease” J. Am. Ger. Soc. (2000), 48 pp 1566-1571
8. Alvarez X, Moessler H, “Efficacy of Cerebrolysin in moderate to moderately severely Alzheimer’s disease” In. Vellas B (ed), research and practice in Alzheimer’s disease, Serdi, Paris (2001), pp 179-186
9. Ruether E, Husmann R, Kinzler E, et al, “A 28 week, double blind, placebo controlled study with Cerebrolysin in patients with mild to moderate Alzheimer’s disease” Int. Clin. Psycopharm. (2001), 16 pp 253-263
10. Panisset M, Gauthier S, Moessler H, et al. “Cerebrolysin in Alzheimer’s disease; a randomized, double-blind, placebo controlled trial with a neurotrophic agent” J. Neural. Transm. (2002)
11. Rainer M, Brunnbauer M, Dunky A, et al. “Therapuetic results with Cerebrolysin in the treatment of dementia” Wiener Medizinische Wochenschrift (1997), 147 pp 426-431.
12. Alvvarez XA, Cacabelos R, Laredo M, Couceiro V, Sampedro C, Varela M, Corzo L, Fernandex-Nopvoa L, Vargas M, Aleixandre M, Linarges C, Granizo E, Muresanu D, Moessler H, “A double blind, placebo controlled study of three dosages of Cerebrolysin in patients with mild to moderate Alzheimer’s disease” Eue. J. Neurol. 2006 Jan 1;13 (1) 43-54

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