Cerebrolysin
Cerebrolysin is a protein-based agent that exhibits unique neurotrophic (assisting growth) and neuroprotective activity. It has been studied in thousands of patients in double-blind studies with consistently excellent results. Some of the effects include:
Protects nerve cells from damage
Decreases damage from excitotoxic effects
Blocks over activity of calcium dependent proteases (this reduces spasm)
It scavenges free Oxygen radicals
It increases nerve viability and survival during and after ischemic events (lack of oxygen)
Slows progressive global and cognitive decline (helps prevent mental decline)
As these effects are widespread, Cerebrolysin can be used for a large number of conditions. These include:
Any organic, neurologic, and degenerative disorders of the brain
Alzheimer's and dementia
Neurological trauma of any type
Any conditions with low oxygen as a component
Cerebrolysin can be used either for acute stroke or later for rehabilitation. When used for dementia/Alzheimer's, it is able to stop the progression of the disease and also improve the current symptoms. Cerebrolysin is given via intravenous infusion, unless a very small dose is used. It is administered one time per day, five times per week, for a total of 20 treatments. The treatment is then stopped for 4 weeks, after which the cycle can repeat as often as needed.
No safety concerns were noted during clinical trials. Side effects were rare, and at the same frequency in groups getting the active agent or the placebo. The most common events were vertigo, agitation, and feeling hot, all of which were mild and short-lived.
In summary, Cerebrolysin is a safe, effective therapy that can be used for nearly any problem involving the brain.
Cerebrolysin studies
The effects of Cerebrolysin have been investigated and confirmed in various cell culture and animal models of neurodegeneration and ischemia.
For example, in ApoE knock-out mice, which suffer from early neuronal degeneration, Cerebrolysin treatment reversed cognitive impairment (Masliah E et al., 1999; Rockenstein E, 2002). Treatment for 4 weeks also reestablished normal MAP2 levels in the frontal cortex, increased the synaptic density and had morphological effects. These results suggest a normalization of neuronal cytoarchitecture compared to controls.
In a gerbil model of cerebral ischemia/reperfusion, Cerebrolysin decreased hydroxyl radical formation in the cerebral cortex and hippocamus. A significant number of pyramidal and hippocampal neurons in the CA1 region were saved (Sugita Y et al., 1993).
Stroke therapy
Stroke is the third most common cause of death worldwide. Damage from stroke has frightening proportions. Data from the US show that 157,991 people there were killed by a stroke in 1995; more than 700,000 people per annum suffer a stroke; and about 4.4 million US residents are stroke survivors. The yearly economic burden of stroke was about $51 billion in 1999. The incidence of stroke is rising every year.
But stroke is neither unpreventable nor untreatable. Early recognition, treatment in »stroke units«, and the attempt to treat the patients as early as possible have led to huge improvements in survival and rehabilitation. Unfortunately, stroke patients still wait, on average, for 13 hours before presenting at the emergency department and receiving treatment.
Neuroprotective and neurotrophic agents have opened new avenues in stroke treatment and increase the potential for survival and rehabilitation, even for patients who are unlucky enough to present later than the critical window of 3 hours after the event. Next to thrombolysis, protection of vulnerable neurons with neuroprotective agents has become the premier option for the treatment of ischaemic stroke.
Cerebrolysin, a neuroprotective and neurotrophic drug containing peptides with unique biological activity, protects the nerve cells from the hazards of the ischemic cascade. Cerebrolysin reduces excitotoxic damage, blocks overactivation of calcium-dependent proteases, and scavenges free oxygen radicals. It increases neuronal viability and survival during and after ischemic events.
Clinical trials with Cerebrolysin demonstrate that it is significantly effective in acute stroke and stroke rehabilitation and improves neurological function, global scores, activities of daily living, and cognitive performance. Trials of Cerebrolysin in stroke encompass more than 1,500 ischaemic stroke patients.
Randomised, double-blind, placebo-controlled clinical trials with Cerebrolysin in stroke
Barolin GS et al. (1996) 418 Patients with Acute Ischaemic Stroke
and During Early Rehabilitation
Haffner Z et al. (1999) 48 Patients with Acute Ischaemic Stroke
Herrschaft H et al. (1998) 69 Patients with Acute Ischaemic Stroke
Ladurner G et al. (2000) 146 Patients with Acute Ischaemic Stroke
and During Early Rehabilitation
Muresanu DF (1999) 60 Patients with Acute Ischaemic Stroke
Wege HW et al. (2001) 60 Patients with Acute Ischaemic Stroke
and During Rehabilitation
Open-label clinical trials with Cerebrolysin in stroke
Domzal T et al. (1995) 131 Patients with Acute Ischaemic Stroke
Gusev EI et al. (1994) 60 Patients with Acute Ischaemic Stroke
Volc D et al. (1998) 331 Patients with Acute Ischaemic Stroke
and During Rehabilitation
Safety of Cerebrolysin
No safety concerns for Cerebrolysin were noted in clinical trials. Adverse events (AEs) were rare and equally frequent in Cerebrolysin-treated groups or control groups. Most common AEs included vertigo, agitation and feeling hot. All AEs were mild and transient. There were no changes in the vital signs of the patients nor in any of the lab parameters.
An important fact: Cerebrolysin can be used safely in patients with acute haemorrhagic stroke (Shi Y et al., 1990). This allows the critical period to the start of treatment to be shortened, because Cerebrolysin can be given immediately, without waiting for brain imaging results. For further information please go to "Clinical safety".
Safety of Cerebrolysin is assured through many years of clinical application, information from post-marketing surveillance studies, and safety data from randomized, controlled clinical trials. Reported events from all sources indicate that adverse reactions due to the drug generally are mild in intensity and transient. There is no evidence for systemic toxicity. Data from double-blind, placebo-controlled clinical trials clearly demonstrate an incidence rate of adverse events under Cerebrolysin treatment similar to that of placebo-treated patients.
Following table gives an overview of all adverse events reported in clinical trials, summarized by body systems according to COSTART:
Body as a whole74
Cardiovascular system98
Digestive system73
Endocrine system1
Hemic and lymphatic system6
Injection site reaction4
Metabolic and nutritional disorders11
Musculoskeletal system3
Nervous system213
Respiratory system38
Skin and appendages15
Special senses5
Urogenital system5
546
Of these 546 reported adverse events, the most frequent were:
Headache41
Vertigo31
Nausea24
Increased sweating21
Agitation20
Fever18
Hypertension18
Hallucinations14
Hypotension11
Confusion10
Flu syndrome10
These data were derived from 8,057 patients, corresponding to an incidence rate of 6.77 events per 100 patients.
The folowing table gives an overview of all adverse events reported from ongoing post-marketing surveillance studies, summarized by body systems according to COSTART:
Body as a whole 7
Headache 4
Fever 2
Asthenia 1
Cardiovascular system 16
Vasodilation 10
Tachycardia 4
Hypertension 1
Phlebitis 1
Digestive system 5
Nausea/vomit/malaise 3
Diarrhea 2
Nervous system 39
Vertigo 15
Agitation 11
Nervousness 7
Confusion 3
Hostility 3
Skin and appendages 3
Allergic cutaneous reaction 2
Pruritus 1
70
These data derived from 2,986 patients corresponding to an incidence rate of 2.34 events per 100 patients.
The accumulated evidence demonstrates that Cerebrolysin is safe and well tolerated.
Therapeutic indications
Organic, metabolic and neurodegenerative disorders of the brain, especially senile dementia of Alzheimer's type
Post-apoplectic complications
Craniocerebral trauma; post operative trauma, cerebral contusion or concussion
Contraindications
Hypersensitivity to one of the components of the drug
Epilepsy
Severe renal impairment
Special warnings and special precautions for use
Special care is indicated in cases of:
allergic diathesis
epileptic conditions and grand mal convulsions; Cerebrolysin treatment may result in an increase in the frequency of seizures
although there are no indications that Cerebrolysin causes renal stress, the product should not be administered in the presence of existing severe renal insufficiency
Interaction with other medicaments and other forms of interaction
On the basis of Cerebrolysin's pharmacological profile, special attention should be given to possible additive effects when used in conjunction with anti-depressants or MAO-inhibitors. In such cases it is recommended that the dose of the anti-depressant is lowered.
Cerebrolysin should not be mixed with balanced aminoacid solutions in an infusion.
Pregnancy and lactation
Animal studies did not show any indication of reproductive toxicity. However, no data is available for humans. Therefore, during pregnancy and lactation, Cerebrolysin should only be used after careful risk/benefit considerations.
Effects of the ability to drive and use machines
Clinical tests of Cerebrolysin have shown no effects on ability to drive a car or operate machinery.
Undesirable effects
In rare cases the desired effects of activation have also been associated with agitation (aggression, confusion, insomnia).
In one study rare cases of hyperventilation, hypertonia, hypotonia, tiredness, tremor, depression, apathy, dizziness and symptoms of influenza (eg. cold, cough, infections of the respiratory tract) were reported.
Single cases of grand mal attack and convulsions have been reported with Cerebrolysin.
In rare cases, gastro-intestinal disturbances, such as loss of appetite, dyspepsia, diarrhea, constipation, vomiting and nausea, have been observed.
If injected too quickly, feelings of heat or sweatiness, dizziness, and, in isolated instances, palpitations or arrhythmias may result.
Injection site reactions, such as erubescence, pruritus and burning have been reported.
In very rare cases, hypersensitivity or allergic reactions such as skin reactions, local vessel reactions, headache, neck pain, limb pain, fever, lower backache, dyspnoea, chills and shock like state have been observed.
As Cerebrolysin is used in the elderly, the above-mentioned undesirable effects are typical of this patient population and may be observed without drug use.
Overdose
There are no known instances of health related negative effects due to overdose or intoxication.
Dementia
Introduction
Dementia is the fourth most common cause of death in G7 countries and will be so worldwide soon. The human and economic costs are enormous. Dementia is estimated to cost 100 billion dollars per year in the US, and the incidence is rising every year. However, if onset could be delayed on average for only one year, in the US there would be ~210,000 fewer persons afflicted with this disease after 10 years. This would result in annual savings of nearly 10 billion US dollars.
Currently, therapy of dementia is focused on symptomatic treatment. Neurotrophic agents open new avenues in dementia treatment and may be able to modify the underlying disease. Cerebrolysin, a unique neurotrophic and neuroprotective drug containing biologically active peptides, can slow down the progressive global and cognitive decline of dementia patients.
Data from recent clinical trials show that Cerebrolysin has a stabilising effect in patients with demen?ia, and demonstrate that it is significantly efficacious in cognitive function, global scores, and activities of daily living. Cerebrolysin induces long-term benefits, with sustained improvements for at least three months after withdrawal. Trials of Cerebrolysin in dementia encompass more than 2,500 patients. Safety data show that Cerebrolysin is well tolerated.
Randomised, double-blind, placebo-controlled clinical trials with Cerebrolysin in dementia
Bae CY et al. (2000) 58 Patients with AD
Panisset M et al. (2000) 192 Patients with AD
Ruether E et al. (2001) 149 Patients with AD
Ruether E et al. (1994) 120 Patients with AD
Ruether E et al. (2000) Follow-Up of Above1994 Clinical Trial
Xiao S et al. (2000) 157 Patients with AD
Vereshchagin NV et al. (1991) 60 Patients with VD
Xiao S et al. (1999) 148 Patients with VD
Open-label clinical trials with Cerebrolysin in dementia
Gavrilova SI et al. (1998) 55 Patients with AD
Iakhno NN et al. (1996) 20 Patients with VD
Rainer M et al. (2000, 1997) 1.006 Patients with AD
Takahashi M et al. (1993) 22 Patients either with AD or with VD
The neurotrophic drug Cerebrolysin leads to statistically and clinically significant improvements in cognitive performance, global function, and activities of daily living of patients with dementia.
Patients on Cerebrolysin experience symptomatic improvement after only one month of treatment, which can be reinforced with a second treatment course. Beyond its symptomatic benefit, Cerebrolysin demonstrates a stabilizing effect on the pathological process and patients show sustained treatment benefit even after drug withdrawal. The safety profile of Cerebrolysin is excellent with only rare and benign side-effects.
Cerebrolysin is safe and effective in dementia.
