NeuroSearch demonstrates the potential of ACR16 as a novel treatment for Huntington’s disease

NeuroSearch demonstrates the potential of ACR16 as a novel treatment for Huntington’s disease

Preclinical and early clinical data presented at the 4th Huntington’s Disease Therapeutics Conference in Cannes, France

Today, NeuroSearch presents data on the mode of action and the preclinical pharmacology of ACR16, demonstrating the unique functional activity of the company’s novel drug candidate in

development for Huntington’s disease.

Furthermore, preclinical and clinical results also presented today, demonstrate the potential of ACR16 as an effective and novel treatment for Huntington’s disease symptoms, for which no effective treatment exists currently. In particular, patients with Huntington’s disease experience reduced motor performance, cognitive impairment and depressed mood, and ACR16 may be effective in targeting both the motor and behavioural symptoms of the disease. A pivotal development programme is underway, with the results from a large European Phase III Huntington’s disease study expected around the turn of the year.
The preclinical and early clinical data on ACR16 will be shown today, Wednesday 29 April 2009 at 2:30 pm CET at the 4th Huntington’s Disease Therapeutics Conference held in Cannes, France in the form of two poster presentations. Details of the posters and the main findings follow:

“Preclinical pharmacology and mode of action of the dopaminergic stabilizer ACR16”,By S Waters, F Petterson, T Dyhring, C Sonesson, J Tedroff, N Waters, H Pontén
In vitro binding studies show that ACR16 binds to the dopamine D2 receptor, with a slight preference towards the high affinity (activated) receptor state.

ACR16 differs from dopamine D2 receptor antagonists, agonists and partial agonists:
Unlike classical D2 antagonists, ACR16 antagonises dopamine-dependent D2 activation with fast-off kinetics. Unlike agonists and partial agonists, it has no detectable agonist activity at the D2 receptor. These in vitro findings suggest that ACR16 would be able to allow the physiological effects of dopamine surges.

In vivo, ACR16 strengthens glutamate function in the frontal cortex. This phenomenon, which is not observed with classical D2 antagonists or partial agonists, may add to the novel agent’s powerful in vivo behavioural effects in states of excessively high dopamine activity or excessively low glutamate activity, while not affecting behaviour under normal conditions.
Together, these findings suggest that ACR16 stabilizes psychomotor activity in states of hypo- and hyperactivity, by means of functional D2 antagonism and strengthening of cortical glutamate functions; offering the potential for clinical relief of psychomotor symptoms arising from dopaminergic dysfunction in conditions such as Huntington’s disease.

“Rationale for ACR16 as a symptomatic treatment for Huntington’s disease”,By M Esmaeilzadeh MD, J Tedroff MD, PhD

ACR16 represents a novel class of functional modulators of the dopaminergic system (i.e. dopaminergic stabilizers), which primarily interact with D2-type receptors.Unlike other compounds acting on D2 receptors (e.g. neuroleptics and partial dopamine agonists), the effect of ACR16 extend beyond the dopaminergic system, leading to strengthened cortical control of the striatum.

Early clinical studies with ACR16 have been encouraging in terms of reducing Huntington’s disease symptoms, without producing unwanted side effects.
Joakim Tedroff M.D., Ph.D, Medical Director of NeuroSearch Sweden AB comments:
“Huntington’s disease is a very serious condition associated with a complex mixture of motor dysfunction, cognitive decline, and behavioural difficulties. So far, no treatment has been able to effectively help improve life for Huntington patients, and therefore we are encouraged by these results from early clinical studies with ACR16, which suggest that it has the potential to provide relief for a number of the symptoms associated with this devastating brain disorder. We are currently evaluating ACR16 in a comprehensive pivotal programme, including a total of 640 patients with Huntington’s disease in both North America and Europe, and the first results are expected around the turn of the year.”