PDE4 re-emerges as depression therapy
(PDE4) inhibitor in depression, resurrecting the use of this class
of drug in this indication.
The decision to advance the drug, called ND1251 into clinical trials comes after animal studies suggested that it did not exhibit typical side effects that have held back the clinical use of previously developed PDE4 inhibitors.
Charles Woler, CEO of Neuro3d said: "Depression will be the initial focus for ND1251 because of the documented success of PDE inhibition in this indication and the significant medical need for new types of treatments."
"We believe that there may be several more applications both core and non-core to our business."
Lubor Gaal, head of business development and liscensing told DrugResearcher.com: "This is not the first time a PDE4 inhibitor has been used to treat depression. Rolipram was first investigated as an antidepressant by the German pharmaceutical company Schering AG. It was never fully developed however because of the nausea and vomiting it caused."
In preclinical studies, ND1251 has shown antidepressant, memory enhancing and anti-inflammatory effects. On the basis of these activities ND1251 may also have applications in other disorders, such as multiple sclerosis and certain respiratory diseases.
Gaal added: "ND1251 works by inhibiting the enzyme phophodiesterase. This increases the intracellular concentration of cAMP, a second messenger, which regulates enzymes involved in energy metabolism and cell division. This appears to play an important role in brain function."
Gaal explained that the ongoing human trials involved eight volunteers per experimental group who took oral doses of the drug at varying concentrations. The aim was to determine the maximum dose. The degree of brain activity is being measured by electroencephalogram (EEG).
"The tests show ND1251 to be effective in enhancing the memory. This could well have implications for producing a viable therapy for Alzheimers or mild cognitive impairment," said Gaal.
The potential success of ND1251 and Neuro3d's other product, ocaperidone, an antipsychotic, expected to complete Phase lla in 2004, has raised talk of deals with potential partners.
Woler said: "We believe that there may be several more applications both core and non-core to our business. We would of course leverage non-core applications in potential deals with partners."
Gaal added: "We are at an early stage in the research and development of ND1251. The ongoing trials are expected to finish by the second quarter of 2005. If all goes well we can expect to move on to Phase II which we will do with or without a partner."
"What we are looking to do regarding plans for licensing is to form a partnership with a larger company to test and produce the drug on a much grander scale. There is so much potential in this drug which we are keen to exploit which we cannot do alone."
Global drug sales of $19.5 billion in 2003, an increase of 10 per cent from 2002 make depression the largest single market in the central nervous system category.
The World Health Organisation (WHO) estimates that about 340 million people suffer from depression worldwide but only 20 per cent of patients with clinical depression receive treatment.
