Treatment for Alzheimer's patients with depression

Highlights

• Ladostigil, a novel cholinesterase and brain selective monoamine oxidase (MAO) inhibitor for the treatment of dementia co-morbid with depression
• Patients with Lewy body dementia also have a loss of striatal dopamine and symptoms of Parkinson's disease
• Corrects memory impairment in rodents and in aged monkeys resulting from cholinergic hypoactivity.

Our Innovation

• Ladostigil was designed to provide a combination of the improved cognitive function exhibited by inhibitors of both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), antidepressant activity exhibited by MAO -A inhibitors, with neuroprotection against oxidative stress shown by MAO- B inhibitors. This makes ladostigil a promising candidate for the treatment of Alzheimer's disease co-morbid with depression and/or Parkinson's disease

Key Features

• Slower onset of action and therefore a lower incidence of nausea and vomiting than  rivastigmine
• Longer duration of action than rivastigmine
• Prevents depressive-like behaviour in rats without causing significant potentiation of the cardiovascular effect of tyramine in rodents, primates and human subjects
• Neuroprotective activity against oxidative stress in cell culture and in vivo, including the prevention of development of spatial memory deficits in aged rats
• Increases striatal dopamine in the brain

Status of Clinical Trials

• Following the successful completion of chronic toxicity tests in non-human primates, mutagenicity studies, Phase I of clinical studies in young and older healthy individuals and  those with Alzheimer disease have demonstrated that the drug is well-tolerated, with no significant adverse effects and with a lower incidence of gastro-intestinal disturbances that is seen with other cholinesterase inhibitors. There were no significant cardiovascular responses to an oral tyramine challenge after several weeks of chronic treatment with highest dose.
• Clinical studies encompassed:  
• Dose escalation, acute and chronic dosing in normal human volunteers to find (maximal tolerated dose (MTD)
• Dose escalation, chronic treatment with up to 140 mg bid in healthy elderly and patients with AD to find MTD
• Measurements of AChE and BChE activity in blood and MAO-B activity in platelets
• Determination of metabolite profile
• Cardiovascular response to oral tyramine

The Opportunity

• The market for Alzheimer's therapy in the seven major pharmaceutical markets is expected to grow to 21 million people by 2010.
• 50% of Alzheimer's patients experience depression and about 30-40%, have extrapyramidal symptoms
• The major unmet needs of the Alzheimer's market are for disease modification and disease prevention.
• Alzheimer's drugs in seven major markets to reach $7.8billion by 2010

A wide portfolio including 11 patents and patent applications protecting the compounds, derivatives, formulations, methods for preparations and uses.