RESEARCH PROGRAM

Alzheimer’s Disease

To date, Prana research has primarily focused on Alzheimer‘s Disease (AD). AD is a progressive brain disorder that gradually degrades the sufferer‘s memory and ability to learn, communicate and perform daily activities. The disease affects a significant percentage of the population and in an aging society the need for an effective therapy is expected to double over the next 20 years.

There is general consensus amongst researchers that the Abeta protein which forms deposits (plaques) in the brains of Alzheimer‘s patients is responsible for the neuronal dysfunction which manifests as dementia. Over more than a decade of research, Prana scientists have evolved a comprehensive theory explaining how the production, toxicity, aggregation and clearance of Abeta is inextricably linked to pathological interactions between this otherwise benign protein and trace metals vital to normal brain function. MPACs and other drugs in the Prana pipeline have been developed with the aim of preventing such abnormal interactions to prevent protein aggregation and restore the metal balance.

Prana has close collaborative ties with the large neurodegeneration group affiliated with the University of Melbourne/Mental Health Research Institute led by Laureate Professor Colin Masters and Professor Ashley Bush, and the team led by Professor Rudi Tanzi of the Genetics and Aging Research Unit, Massachusetts General Hospital.

As shown in the Asset Pipeline diagram, Prana‘s lead compound PBT2 has completed Phase IIa clinical trial in patients with early Alzheimer's Disease. Planning is currently underway for a Phase IIb clinical trial of PBT2 in patients with mild - moderate Alzheimer's Disease.

Prana is currently validating candidate leads from its MPAC library in the selection of PBT3 and PBT4 series compounds to be designated as follow ups of PBT2 in AD, or for use in secondary alternative indications.

Parkinson’s Disease

Parkinson’s Disease (PD) is a progressive degenerative neurological condition involving damage to cells which secrete dopamine (a chemical transmitter) in the brain, causing abnormality of movement. Sufferers exhibit the three major symptoms of tremor, rigidity (a stiffness of the muscles) and akinesia (abnormal movement). In a similar manner to Alzheimer‘s Disease, the condition is associated with deposits of the protein alpha synuclein and abnormally high levels of iron in the affected areas of the brain.

It is estimated that there are about 100,000 people living with Parkinson‘s in Australia. One in seven people living with Parkinson‘s is under the age of 40, but the average age of diagnosis is around 65 years. Worldwide prevalence of Parkinson‘s varies from between 1 in 1000 to 2 in 1000 with the figure increasing to 1 in 100 over the age of 60. Existing medications for PD offer limited symptomatic relief but do not significantly alter the course of the disease.

A long-standing collaboration with Professor Julie Anderson of the Buck institute for Age Research in Novato CA, provided evidence that drugs of the type being developed by Prana for Alzheimer‘s Disease may also prove to be effective in Parkinson‘s disease. Results published in the prestigious journal Neuron in March 2003 indicated that by blocking anomalous interactions with iron in the brain, PBT1 could prevent the acute brain damage seen in a widely used mouse model of Parkinson‘s Disease. With this proof of principle evidence in hand, the Prana research team is actively investigating the potential of its library of drugs for similar or superior activity in mouse models for PD.

Huntington’s Disease

Huntington‘s Disease (HD) is an inherited (genetic) neurological disorder affecting up to 8 people per 100,000 worldwide. HD, one of a family of polyglutamine (or "Poly Q") diseases, is caused by a mutation in the gene which instructs brain cells to make the Huntingtin protein. As a consequence, an altered form of the protein is deposited and aggregated in select areas of the brain resulting in neuronal cell damage and eventually death. Currently there is no therapy for HD.

Dr. Steven Hersch of Massachusetts General Hospital/Harvard Medical School has shown that aberrant interactions with copper and/or iron may be responsible for the neurodegeneration in HD. These findings offer a mechanistic explanation for the observation published in PNAS in 2005 by consultant Dr Stephen Massa (UCSF), that clioquinol has therapeutic benefit in a genetic mouse model for HD. More recently, Dr Massa has also demonstrated that Prana‘s lead compound, PBT2 shows very promising results in the same HD models.

Prana is undertaking collaborative investigations into the potential of its lead compounds for HD therapy in consultation with international patient advocate groups.

Age-related Macular Degeneration

Age-related Macular Degeneration (AMD) is the most common cause of blindness in people over the age of 55 years in the Western World. In this condition, changes in the portion of the retina called the macula result in irreparable damage to eyesight. Several lines of evidence suggest that age related changes in the distribution of zinc in the retina may be relevant to the cause or progression of the disease. Prana has initiated a research collaboration wth investigators at University College London to evaluate MPAC lead compounds for their potential utility in AMD.

Cancer

In recent years numerous scientific articles have suggested that drugs which target aberrant metabolism of trace metals associated with cancer cells may offer a valuable alternative to current therapies. Preliminary investigations by Prana scientists in collaboration with expert consultants in the cancer field have demonstrated the potential of MPACs as chemotherapeutic agents in specific types of cancer, including breast, ovarian and prostate cancer.