Yes I suspect the Grant cover a good percentage of the base DR salaries. Doubt grants get anywhere near the amount for trials.
Have to remember that Prana gets substantial funding in the form of grants from the various Dementia organizations. Plus, they are elgible to submit for federal grants with ODA designation. They should be doing that, high approval rates for promising therapies. That would be a boost for share price as well and alleviate dilution.
Yea..trial cost $$$. Wish people here would stop pushing the AD and just push the HD trial that has actually shown some promises. Get real funds in the door and not from dilution of stock sales to pay salaries of the BOD and ten Doctors.
page 12 of the annual report the company discloses the possibility of prioritizing clinical trials .Only one reason
That's true it does not matter what we say on ymb forum. It's hard to anticipate what FDA will think of the data - it all depends on how it is presented and that's where Shoulson comes in. It's likely that FDA will look at the data presented with sub-analysis that clearly shows a statistical significant improvement in SUVR readings in the greater than 2.5 baseline SUVRs and for all treated patients, with outlier removal, if the company can make the case. This may also translate into a parallel analysis for the hippocampal atrophy results but we don't have a way of knowing about that. In any case, FDA appears to be willing to look at the information beyond the draft trial report as was in the case of INSM.
Dementia has been a priority with the FDA for a while. Prana has to show substantial improvement over available therapies as indicated above. If Prana had not f'ed up the last trial, they would be on fast track status and probably submitting for approval this year, with compassionate use approved by now.
Hopefully, the follow on studies will show the improvement. Prana still has to prove the effectiveness to the FDA's satisfaction, does not matter what we post or say. Once they do that, then the share price will be like JAZZ.
Our understanding of the pathophysiological mechanisms of AD has been significantly enhanced through the application of neuroimaging to visualise these processes in vivo. At the same time, our knowledge of AD pathophysiology is helping to inform new directions for imaging approaches for studying neuropathology. With the focus shifted to earlier diagnosis at a prodromal or even asymptomatic stage of AD, current imaging methods are important to define these stages. Early diagnostic criteria will depend not only on current biomarkers combined in a multimodal approach, but also the development of novel techniques for neuroimaging that may offer more specific biomarkers of disease, intimately reflecting the underlying pathophysiology. This is also important to the efficacy and success of developing new interventions for altering the course of the disease. Ultimately, without effective interventions, the ability to diagnose AD at any stage will allow us to be little more than informed observers to an unfolding health crisis.
Very important conclusion for the future path of AD clinical trials in early AD efficacy and trial participant selection.
"Additionally, the role of metal dyshomeostasis in AD pathogenesis has suggested other approaches to imaging. Variations in Fe distribution in the brain are detectable by MRI [160, 161], thereby suggesting it can be potentially be applied to study the analysis of Fe dysregulation in AD. Techniques to analyse the distribution of Fe through variations in magnetic relaxivity (R and R*) values have been carried out in post-‐mortem AD brains . Nakada et al  utilised SWI in MRI on a 7T scanner to visualise plaque-‐like pathology in patients with AD. However, their sample size was small and their study could not be correlated with histology. Studies of other aspects of AD pathology, such as the strengthening evidence for the primary role of Aβ oligomers in neurotoxicity and the importance of NFTs in the pathology cascade, will require novel neuroimaging developments. Further insights into the molecular aspects of AD may provide opportunities for clinical imaging applications, and enable further progress on defining preclinical AD. Ultimately, neuroimaging based upon AD patholophysiology may bring about the realisation of accurate early diagnosis, thereby providing the opportunity for early preventative interventions, which can be monitored for efficacy by tracking changes in disease processes using neuroimaging techniques."
Sentiment: Strong Buy
A review of ß-amyloid neuroimaging in Alzheimer’s disease
Paul Adlard, Bob Tran, David Finkelstein, Patricia Desmond, Leigh Johnston, Ashley Ian Bush and Gary Egan
Frontiers in Neuroscience
Alzheimer’s disease (AD) is the most common cause of dementia worldwide. As advancing age is the greatest risk factor for developing AD, the number of those afflicted is expected to increase markedly with the aging of the world’s population. The inability to definitively diagnose AD until autopsy remains an impediment to establishing effective targeted treatments. Neuroimaging has enabled in vivo visualisation of pathological changes in the brain associated with the disease, providing a greater understanding of its pathophysiological development and progression. However, neuroimaging biomarkers do not yet offer clear advantages over current clinical diagnostic criteria for them to be accepted into routine clinical use. Nonetheless, current insights from neuroimaging combined with the elucidation of biochemical and molecular processes in AD are informing the ongoing development of new imaging techniques and their application. Much of this research has been greatly assisted by the availability of transgenic mouse models of AD. In this review we summarise the main efforts of neuroimaging in AD in humans and in mouse models, with a specific focus on β-‐amyloid, and discuss the potential of new applications and novel approaches.
Sentiment: Strong Buy
Thnaks ITM, these FDA priorities with Ira Shoulson's knowledge and will to help patients with neurodegenerative diseases combined with Prana's scientists' innovation ( 1500 MPACs) will change the treatment of these difficult diseases.
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4) Facilitate the application of advanced technologies and methods and relevant scientific discoveries—such as newly identified clinical biomarkers, adaptive clinical trial designs and genomics—to regulated medical products."
Sentiment: Strong Buy
FDA has just published its strategic priorities for the next four years. The objective 2.2 directly relates to the development process being sought by Prana for PBT2 and eventually PBT434 as early as post Phase 1. Just to highlight that this is a priority of FDA over the next 4 years in addition to facilitating the use of novel biomarkers likely needed to assess PBT2 efficacy in early AD.
FDA Strategic priorities 2014-2018
FDA’s core mission goals and objectives are:
Goal 1: enhance oversight of FDA - regulated products
Goal 2: improve and safeguard access to FDA -regulated products to benefit health
Goal 3: Promote better informed decisions about the use of FDA -regulated products
Goal 4: Strengthen organizational excellence and accountability
Objective 2.2: Improve the effectiveness of the product development process
"In addition, FDASIA established breakthrough therapy designation for drugs where preliminary clinical evidence indicates that the drug may offer substantial improvement over available therapies to treat a serious condition. Sponsors of products that are designated as breakthrough products can take advantage of all the features of fast track designation, and receive more intensive guidance from FDA to help them design an efficient drug development program, beginning as early as phase one clinical trials.
Over the next four years, FDA will focus on ways to improve the effectiveness of the product development process by implementing the following strategies:
1) Improve the evaluation of methods, tools, models (e.g., animal, physiological, computer-based) that are used in the development and testing of medical products
2) Advance the development of medical products for rare diseases
3) Enhance communication between FDA and sponsors during the medical product development process
4) Facilitate the application of advanced technologies and methods and relevant scientific discoveries—such as newly identified clinical biomarkers, adaptive c
Sentiment: Strong Buy
his is potentially important for the IMAGINE trial as the potential cause of the heterogeneity of the patient population.
Journal of Huntington's Disease
Volume 3, Number 2 / 2014
Marie Y. Davis1, 2, C. Dirk Keene3, Suman Jayadev1, Thomas Bird1, 4
Background: Dementia is a common feature in both Huntington's disease (HD) and Alzheimer's disease (AD), as well as in the general elderly population. Few studies have examined elderly HD patients with dementia for neuropathologic evidence of both HD and AD. Objective: We present neuropathological findings in a retrospective case series of 15 elderly HD patients (ages 60–91 years), 11 of whom had prominent clinical dementia. Methods: Post-mortem brain tissue was examined and stained for evidence of both HD and AD including Vonsattel grading and Htt-repeat expansion, Bielskowsky, tau, β amyloid, and TDP43 immunostaining. Results: Mean age at death was 76.8 years, mean disease duration was 18.6 years, and mean CAG repeat expansion was 42. Evidence of AD in addition to HD pathology was present in 9 of 11 (82%) patients with prominent dementia, suggesting that AD may be more commonly co-occurring with HD than previously appreciated. Two patients had only HD as the basis of dementia and four patients did not have prominent dementia. One patient with marked parkinsonian features was not L-dopa responsive and had no substantia nigra Lewy bodies at autopsy. Conclusions: Our study suggests that AD may frequently contribute to cognitive decline in elderly HD patients which complicates the assessment and management of such individuals. Further study is needed to determine if there is a higher incidence of AD in persons with HD compared to the general population. In addition, our series includes one HD patient whose clinical features masqueraded as Parkinson's disease but was not responsive to levodopa therapy.
Sentiment: Strong Buy
From this it seems that PBT2 may help for PD as well in terms of prevention if taken early in progression. Yet another reason why PBT2 should get to market ASAP. So possibly the cocktail for PD would include PBT2 and PBT434.
Sentiment: Strong Buy
Abstract from Ashley Bush's talk in Japan
Metallostasis in Alzheimer's disease and Parkinson's
1Ashley I. Bush*
1Florey Institute for Neuroscience and Mental Health, University of Melbourne, Victoria, Australia.
The brain houses high concentrations of transition metals Zn, Cu and Fe. Zn and Cu are released during glutamatergic neurotransmission, and their reuptake fatigues with age. This increases the average concentration of extracellular Zn and Cu (a phenomenon called "metallostasis") leading to A aggregation in
Alzheimer's disease (AD) and other downstream pathologies. Intraneuronal cortical Fe metallostasis is a feature of aging, and is exaggerated in AD where Fe is trapped by neurofibrillary tangles. A marked rise in Fe in the substantia nigra is a feature of both mutation-associated and sporadic Parkinson’s disease (PD). We
hypothesized that the main proteins implicated in the pathology of AD and PD are in proximity to these metals because they function to regulate neuronal metal homeostasis.
1. APP is the neuronal chaperone of ferroportin and is needed for Fe efflux. It is decreased in the SN in PD.
2. PBT2, a Zn/Cu ionophore that has induced cognitive improvement in phase 2 testing in AD, reverses metallostasis.
3. Tau knockout mice accumulate Fe in the cortex and nigra, causing neuronal loss, parkinsonism and cognitive loss with advancing age. The neurodegeneration is inhibited by Fe-chelator treatment. Soluble (functional) tau levels are decreased in AD and PD.
4. Loss of Zn flux in the glutamatergic synapse causes accelerated age-dependent cognitive decline in ZnT3 ko mice, a phenocopy of AD.
5. Presenilins 1 and 2 play major roles in the uptake and turnover of Zn and Cu. The SOD1 activation pathway is sensitive to PS loss.
Metallostasis may be the upstream factor that leads to proteostasis in AD and PD and is an upstream target for new pharmacological approaches.
Sentiment: Strong Buy
As I learned from Eso yesterday the top holder shown on the PBT list includes the ADR shares. The list I printed from the annual is PBT shares We don't have an update on the ADR holdings since June 30.