New drugs to find the right target to fight Alzheimer's disease

A favorite Alzheimer's target: gamma secretase

The two next-generation classes of compound that are currently in clinical trials target an enzyme that cuts APP, known as gamma secretase. Until now, our understanding of the mechanism involved has been lacking. But with this work, the EPFL researchers were able to shed some more light on it by determining how the drug compounds affect gamma secretase and its cutting activity.

In most forms of Alzheimer's, abnormally large quantities of the long amyloid peptide 42 -- named like that because it contains 42 amino acids  are formed. The drug compounds change the location where gamma secretase cuts the APP protein, thus producing amyloid peptide 38 instead of 42, which is shorter and does not aggregate into neurotoxic plaques.

Compared to previous therapeutic efforts, this is considerable progress. In 2010, Phase III clinical trials had to be abandoned, because the compound being tested inhibited gamma-secretase's function across the board, meaning that the enzyme was also deactivated in essential cellular differentiation processes, resulting to side-effects like in gastrointestinal bleeding and skin cancer.

"Scientists have been trying to target gamma secretase to treat Alzheimer's for over a decade," explains Patrick Fraering, senior author on the study and Merck Serono Chair of Neurosciences at EPFL. "Our work suggests that next-generation molecules, by modulating rather than inhibiting the enzyme, could have few, if any, side-effects. It is tremendously encouraging."

Ref : http://www.nature.com/ncomms/2013/130802/ncomms3246/full/ncomms3246.html

New drugs to find the right target to fight Alzheimer's disease

NDA of Lurasidone for Schizophrenia...

In continuation of my update on  Lurasidone, ........

Dainippon Sumitomo Pharma America, Inc. (DSPA), a U.S. subsidiary of Dainippon Sumitomo Pharma Co., Ltd. (DSP), submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for lurasidone, an investigational atypical antipsychotic agent for the treatment of schizophrenia. The application, submitted on December 30, 2009, includes data from more than 40 clinical studies involving more than 2,500 lurasidone-treated patients.The efficacy of once-daily lurasidone was demonstrated in four six-week, placebo-controlled studies, involving hospitalized patients with schizophrenia. These studies included the global PEARL 1 and PEARL 2 clinical trials....

Ref : http://dsp-america.com/pdf/news/Lurasidone_NDA_Submission_PR_Jan_2010.pdf

FDA approves Olanzapine as Extended Release Injectable Suspension.....

In continuation of my update on drug development for schizophrenia , am sharing this info. The U.S. Food and Drug Administration (FDA) approved ZYPREXA RELPREVV (olanzapine) For Extended Release Injectable Suspension for the treatment of schizophrenia in adults. Different from both oral and injected short-acting formulations, long-acting formulations of antipsychotics allow for stable concentrations of the active drug to remain at a therapeutic range for an extended period of time.

The FDA approval is based on a broad clinical data package involving 2,054 patients, in which ZYPREXA RELPREVV was found to be effective in controlling symptoms of schizophrenia, including hallucinations, delusions, apathy and social withdrawal. Efficacy was shown without the need for oral supplementation. Clinical data showed that ZYPREXA RELPREVV dosages (150, 210, 300 and 405 mg) provide therapeutic olanzapine exposure for two or four weeks depending on the dose. More interesting outcome from these trials is that ZYPREXA RELPREVV was found to have a similar safety profile as oral olanzapine, with the exception of injection-related events, including post-injection delirium/sedation syndrome (PDSS).

PDSS events have occurred in < 0.1 percent of injections and approximately 2 percent of patients. The potential for onset of an event is greatest within the first hour after injection. The majority of cases have occurred within the first three hours after injection; however cases have occurred after three hours. All patients largely recovered within 72 hours.....

Ref : http://newsroom.lilly.com/releasedetail.cfm?ReleaseID=429876

Epilepsy Drugs Could Treat Alzheimer's And Parkinson's

Epilepsy Drugs Could Treat Alzheimer's And Parkinson's

New 'Schizophrenia Gene' Prompts Researchers To Test Potential Drug Target

The newfound gene, dubbed KIAA1212, serves as a bridge linking two schizophrenia genes: DISC1 and AKT. Suspecting KIAA1212 as one of many potential binding partners interacting with DISC1, whose name is an acronym for "Disrupted-in-Schizophrenia," the researchers genetically shut down the production of DISC1 proteins in newly born neurons in the hippocampus region of an adult mouse brain. The hippocampus contains a niche where native stem cells give rise to fully developed new neurons

Read : New 'Schizophrenia Gene' Prompts Researchers To Test Potential Drug Target

Lurasidone - positive results from phase 3 clinical trials !

I  read about this compound few months back, that it is one of  "atypical antipsychotic" drugs that are being tried and this drug has shown promising results in the phase II and is being studied clinically for phase III  by a Japanese company.  

As per the claims by the company 'Lurasidone,  blocks D2- and 5-HT2A-receptors and the advantage is it causes less extrapyramidal side effects than current antipsychotics.

Yes the phase 3 results are really interesting,  with Lurasidone 40 and 120 mg, taken once-daily, demonstrated significantly greater improvement versus placebo on the primary efficacy measure. A total of 53% of patients on lurasidone 40 mg/day and 47% of patients on lurasidone 120 mg/day demonstrated a 30% or more improvement on the PANSS total score from baseline versus 38% on placebo. Lurasidone was also well-tolerated with an overall discontinuation rate similar to placebo (40% vs. 39% placebo) and few adverse event-related discontinuations (9% for both the overall lurasidone group and placebo). Adverse events seen in the trial were generally mild.

Congrats for this achievement. 

Ref : http://dsp-america.com/pdf/news/LurasidonePh3Results.pdf