News and Events

Completion of a study on retinal pathology in an animal model of Parkinson’s disease

Neuropore Therapies Inc. and collaborators at the University of California, San Diego complete a study on the progression of Parkinson’s disease in Laboratory Animals Using Phoenix Research Labs’ Retinal Imaging Technology


Pleasanton, CA, February 10, 2014 — Phoenix Research Labs, Inc., Neuropore Therapies, and UC San Diego today announced breakthrough study results from an industry-academia collaborative effort demonstrating the utility and relevance of Phoenix’s retinal imaging technology as a non-invasive and effective method to evaluate and track the progression of neurodegenerative changes in animal models of Parkinson’s disease. This technology provides researchers with a fundamental new tool for detecting and tracking the progression of the underlying neuropathology in these disorders over time in an individual animal. The ability to non-invasively measure the developing neuropathology within the central nervous system provides investigators with a, previously missing, vital link between behavioral measures of central nervous system function and the underlying neuropathology in living animals.


The study utilized a transgenic mouse genetically engineered by UC San Diego researchers Edward Rockenstein and Dr. Eliezer Masliah to express a fluorescent- tagged version of a key protein involved in the pathology of Parkinson’s disease.  The Phoenix Micron Retinal Imaging Microscope was then used to image this protein in the retina across time during the course of the developing neuropathology in these animals.   The findings from this study clearly demonstrated that progression of the Parkinson’s disease-like pathology could be quantified through eye imaging in a unique mouse model system to evaluate retinal pathology as an additional or alternate indicator for central nervous system neuropathology.  This new approach will provide great assistance to investigators working to discover new therapeutics for Parkinson’s disease.


These findings also point to a possible method for non-invasively measuring this pathological hallmark of Parkinson’ Disease in humans  The identification of a biomarker tool  for the early diagnosis of neurodegenerative disorders and then for following the course of the disorders through time or across different experimental  treatments is vitally important for the development of novel “disease modifying therapeutics and is the focus of large scale collaborative efforts e.g., the Parkinson’s Progression Markers Initiative (PPMI),” said Neuropore Therapies’ Dr. Diana L. Price, Director of Neurosciences.

Figure 3 retinal scan white paper

Fluorescent imaging demonstrates an increased presence of abnormal proteins in the retinae of transgenic animals. These accumulations are similar to those observed in central nervous system studies.

“Being able to assess neurodegenerative diseases using non-invasive means to observe the retina for protein level changes is an exciting development in translational research because of the potential future impact in the clinical arena,” said Phoenix Research founder and CEO, Bert Massie, PhD. “Phoenix is very excited to see the Micron’s unique ability to image fluorescent molecules, yielding data that so clearly aligns with published animal models.”



About Phoenix Research Labs

Phoenix Research Labs is an animal eye research company focused on developing innovative technologies to advance and support in vivo eye and eye-brain research using laboratory animals. The comprehensive suite of Phoenix products includes the Micron IV Retinal Imaging Microscope, Image-Guided Optical Coherence Tomography (OCT) System, Ganzfeld (Electroretinogram) ERG System, Image-Guided Focal (Electroretinogram) ERG System, Image-Guided Laser System and Anterior Segment Image System. With systems located in the US, Europe, Asia and Latin America, Phoenix Research Labs has a global presence in the world ophthalmology research effort. Incorporated in 2008 by Dr. Bert Massie, the company is located in Pleasanton, CA. For more information visit


About Neuropore Therapies

Neuropore Therapies is an innovative biopharmaceutical company utilizing structure-based drug-design technologies to discover novel therapies for Parkinson’s Disease, Alzheimer’s Disease, and related neurodegenerative disorders. Neuropore has developed unique models of the processes by which the abnormal folding and deposition of neuronal proteins leads to synaptic dysfunction and cell death in these disorders. Using these technologies and models, Neuropore has discovered drug-like orally bioavailable compounds that block these pathological processes and dramatically improve outcomes in animal models. Neuropore is advancing it’s lead compounds through preclinical development with the goal of bringing potential new treatments for neurodegenerative disorders into clinical trial. For more information visit


To read the complete “Neuropore Therapies Inc. and collaborators at the University of California, San Diego complete a study on the progression of Parkinson’s disease in Laboratory Animals Using Phoenix Research Labs’ Retinal Imaging Technology” paper click here.


Media Contact (Phoenix Research Labs):

Melody Bertolucci

Director of Marketing



Media Contact (Neuropore Therapies):

Paul Gotfredson, CPA



News and Events

Advancement of NPT200-11 into preclinical development

NeuroPore Therapies, a San Diego based biopharmaceutical company dedicated to the discovery and development of novel therapeutics for neurodegenerative disorders, with support from the Michael J. Fox foundation, has initiated preclinical development  of its lead compound for the treatment of Parkinson’s disease.  This novel compound, NPT200-11,  blocks the pathological protein misfolding, aggregation and deposition that contributes to synaptic dysfunction and cell death in Parkinson’s disease and related disorders.  Moreover, NPT200-11 is orally bioavailable, has promising drug-like properties and, has shown robust beneficial actions on multiple endpoints in animal models.  It is the goal of Neuropore therapies to advance NPT200-11 into clinical trials for evaluation as a novel therapeutic for Parkinson’s disease.

News and Events

2013 ELANS meeting April 25th-28th in San Diego, CA.

The 2013 European Latin American Neurology Symposium (ELANS) took  place April 25th-28th in San Diego, CA.  ELANS is an international meeting for healthcare professionals that focus on the investigation of neurodegenerative and cerebral vascular diseases as well as on the daily clinical practice with affected patients and their surroundings. Clinicians and non-clinical researchers discussed advances in the investigation within that spectrum of diseases, perspectives on outcome, be it short or long term, as well as clinical and ethical questions that arise during the daily work with patients, their families, caregivers and healthcare professionals. Click here to review program.


The 2013 ELANS meeting was organized by EVER Neuro Pharma in cooperation with Neuropore Therapies.


For more information please visit the meeting website at

News and Events

Neuropore presented at the 2013 AD/PD meeting March 4th-10th.

Neuropore scientists presented autophagy program data at the 2013 AD/PD meeting March 4th -10th, in Florence, Italy.


Click here to request a poster reprint.


*Published abstract #A-459-0013-01569, 2013 AD/PD meeting in Florence, Italy.


Development of a novel series of PI3K modulators designed to promote autophagy and the cellular clearance of neurotoxic peptides


Wolf Wrasidlo1,2, Igor Tsigelny2, Diana L. Price1, Douglas W. Bonhaus1, Amy D. Paulino1, Herbert Moessler1,3, Edward Rockenstein2, Eliezer Masliah2


1Neuropore Therapies, Inc., San Diego, CA 92121.
2University of California, San Diego, Department of Neuroscience and the Alzheimer’s Disease Research Center (ADRC), La Jolla, CA 92093.
3EVER Neuropharma, Unterach, AUSTRIA


Background:  Dysregulation of autophagy and consequent cellular accumulation of aberrant toxic protein aggregates may be the common underlying basis of many neurodegenerative disorders. Autophagy can be modulated via the AKT-mTOR pathway and pharmacological inhibitors of this pathway, such as rapamycin acting at mTOR, activate autophagy and to have beneficial effects in animal models of neurodegenerative disorders.

Objectives: Since PI3K regulates the AKT-mTOR pathway we tested whether a novel series of PI3K modulators could affect the AKT-mTOR pathway, increase autophagy and promote the clearance of aberrant neurotoxic proteins.

Methods: Structure-based design was used to generate a series of structurally novel ligands aimed to interact with a selected region of the catalytic domain of PI3K. In vitro and in vivo studies were then conducted to characterize the effects of these molecules on the AKT-mTOR pathway, cellular markers of autophagy and the clearance of amyloid-beta and alpha-synuclein. 

Results: NPT-520-34 inhibited the PI3K-AKT-mTor pathway, promoted autophagy, and reduced Abeta1-42 oligomers or alpha-synuclein accumulation in vitro. NPT-520-34 has favorable ADME properties, good oral bioavailability (29%), and no identified safety issues. In vivo studies confirmed biological activity, promotion of autophagy, and clearance of neurotoxic peptide oligomers.

Conclusions: A novel PI3K modulator, NPT-520-34, reduced alpha-synuclein accumulation and toxicity both in vitro and in vivo by increasing autophagy mediated clearance of oligomers. Studies are underway to assess the utility of NPT-520-34 as a potential therapeutic for the treatment of a wide range of neurological disorders including Alzheimer’s disease, Parkinson’s disease, multiple systems atrophy and dementia with Lewy bodies.


News and Events

UCSD researchers presented in vivo evaluations of NPT compounds at 2012 SFN meeting.

UCSD researchers presented the results of in vivo evaluations of Neuropore synuclein-targeting compounds at 2012 SFN meeting October 13th-17th, in New Orleans, Louisiana.


Click here to request a poster reprint.


*Published, 2012 Society for Neuroscience, Abstract 53.25.


Novel heteroaromatic organic compound normalized calcium abnormalities in α-synuclein transgenic Parkinson’s Disease-like mice model


Reznichenko L.1, Cheng Q.1, Mante M.1, Saisan P.A.1, Rockenstein E.M.1, Overk C.1, Tsigelny I.F.1,3, Wrasidlo W.4,5, Price D.L.5, Dale A.M.1,2, Devor A.1,2,6, Masliah E.1

1Neurosciences, 2San Diego Supercomputer Ctr., 3Moores Cancer Ctr., 4Radiology, UCSD, San Diego, CA;5Neuropore Therapies Inc., San Diego, CA; 6Massachusetts Gen. Hospital, Athinoula A. Martinos Ctr. for Biomed. Imaging, Harvard Univ., Charlestown, MA


Abnormal accumulation of α-synuclein is central to the pathogenesis of many disorders with Parkinsonism and dementia. Recently, using in vivo two-photon laser scanning microscopy, we demonstrated that neurons in the somatosensory cortex of transgenic mice expressing wild-type human α-synuclein exhibit pathological calcium activity. The most evident pathology was observed in response to repetitive stimulation – when subsequent stimuli were presented before the calcium signal returned to baseline – and was characterized by augmented, long-lasting calcium transients with considerable deviation from the exponential decay. These alterations were detected in the absence of a significant increase in neuronal spiking response, consistent with the hypothesis that α-synuclein promotes calcium alterations via interference with intrinsic cellular calcium buffering mechanisms. In the present study, we used this augmented calcium response as an in vivo functional biomarker of pathology and explored the therapeutic potential of a novel α-synuclein stabilizing agent: heteroaromatic organic compound-01 (HAOC-01). HAOC-01 was designed to bind the hydrophobic NAC domain of α-synuclein and to alter α-synuclein monomer structure, preventing binding of the α-synuclein monomer to cellular membranes and other α-synuclein molecules. The drug was administered acutely during an imaging session by intracortical microinjection. We established the pre-treatment baseline in each α-synuclein transgenic mouse by imaging calcium activity in individual cortical neurons in response to a train of 3 sensory stimuli delivered at 3 Hz (electrical whisker stimulation, 1 mA). Calcium measurements were repeated in the same neurons every ~15 min, while HAOC-01 (10 µM) was microinjected into the cortical tissue within the imaged area for 100 ms, 2 s prior to each sensory stimulus delivery. In agreement with our previous data, pre-treated neuronal calcium transients were characterized by an abnormal increase in the amplitude in response to each consecutive stimulus in the train. Administration of HAOC-01 reversed the pathological augmentation in the calcium response ~1 h after the beginning of microinjections. The effect was specific to HAOC-01 because vehicle-treated transgenic mice exhibited no improvement. These results suggest that synuclein-stabilizing agents may normalize α-synuclein-related changes in calcium homeostasis.

News and Events

Neuropore scientists presented at 2012 AAIC meeting July 14th -19th.

Neuropore scientists presented Abeta-protein program data at the 2012 Alzheimer’s Association International Conference (AAIC) meeting July 14th -19th, in Vancouver, British Columbia.


Click here to request a poster reprint.


*Published abstract #29624, 2012 AAIC meeting in Vancouver, B.C. (July 13-19th)




Diana L. Price*1, Wolf Wrasidlo1,2, Igor Tsigelny2, Douglas Bonhaus1, Amy D. Paulino1, Michael Mante2, Chandra Inglis2, Anthony Adame2, Herbert Moessler1,3, Edward Rockenstein2, Eliezer Masliah2


1Neuropore Therapies, Inc.,  San Diego, CA  92121.
2University of California, San Diego, Department of Neuroscience and the Alzheimer’s Disease Research Center (ADRC), La Jolla, CA 92093.
3EVER Neuropharma, Unterach, AUSTRIA



Alzheimer’s disease (AD) is a common, debilitating neurodegenerative disorder afflicting the aging population. Synaptic accumulation of Abeta (Ab)-protein oligomers and tau might be responsible for the neurological damage in AD. Thus, special interest has emerged in developing treatments that reduce the formation or facilitate the clearance of these oligomers. Utilizing molecular modeling and structure based design techniques we generated a series of novel organic heterocyclic compounds that are capable of recognizing the aggregated Ab-protein molecule and promoting clearance. Using cell-free and cell-based assays, a compound denominated NPT-400 with activity in the high nanomolar range was identified for pharmacokinetic (PK) and preliminary efficacy studies in APP transgenic (tg) mice.



The mThy1-hAPP751 transgenic mouse was utilized for efficacy studies. This mouse combines the Swedish (K670M/N671L) and London (V717I) APP mutations, and these animals develop AD-like neuropathology and behavioral deficits starting at 3-4 months of age.   Female non-tg and tg mice (~5 mo of age) received a single injection of vehicle or NPT-400-3 (IP, 10 mg/kg) three times per week for 6.5 weeks.  Behavioral assessments were conducted during week 4 of treatment including locomotor activity and water maze.  At the completion of treatment, brains were hemisected and tissue sections were processed for immunolabeling and confocal analysis, and homogenates were analyzed for levels of Ab-protein by ELISA and immunoblot. For PK studies, wildtype C57Bl6 mice received IV or PO NPT-400-3 compound at 10 mg/kg and blood and plasma levels were analyzed at 0-24 hrs.



Treatment with NPT-400-3 resulted in a statistically significant normalization of locomotor activity accompanied by amelioration of the synaptic and dendritic pathology in the neocortex and hippocampus. By immunoblot and ELISA the levels of monomeric and oligomeric Ab-protein were statistically significantly reduced in the brains of the APP tg mice. PK studies showed that NPT400-3 is stable in plasma, is orally bioavailable and penetrates the brain with a B/P ratio of 0.8 .



NPT-400-3, is an orally bioavailable, brain penetrating Ab-protein stabilizing organic compound that reduces the accumulation of Ab-protein oligomers and ameliorates behavioral deficits and neuropathology in APP tg mice without overt adverse effects.



News and Events

Neuropore presented at 2011 SFN meeting November 12th-16th.

Neuropore and UCSD researchers presented the results of synuclein program experiments at the 2011 SFN meeting November 12th-16th, in Washington, D.C. 


Click here to to request a poster reprint.


*Published, 2011 Society for Neuroscience,   Abstract 357.25.


Novel structure based designed compound reduces accumulation of toxic alpha-synuclein and improves deficits in a transgenic murine model of PD/DLB




1Neuropore Therapies, Inc., San Diego, CA
2Neurosciences, 3Chem. & Biochem., 4Moores Cancer Ctr., UC San Diego, La Jolla, CA


Abnormal accumulation of a neuronal protein alpha-synuclein has been hypothesized to underlie neuronal cell death and dysfunctional connections Parkinson’s Disease (PD) and Dementia with Lewy Bodies (DLB).  We have developed and utilized structure-activity relation (SAR) simulations (Tsigelny et al., 2008) that have allowed us to design and synthesize a novel series of new compounds, including the bicyclic peptidomimetic compound IIPP-1, that hold the promise for the “disease modifying” treatment of PD by selectively blocking the formation/accumulation of toxic forms of alpha-synuclein.  Here we report the results of in vitro characterization, as well as preliminary efficacy studies of IIPP-1 in a transgenic mouse model of PD/DLB.


Evaluation of IIPP-1 in vitro activity demonstrated that this compound potently inhibits the formation of alpha-synuclein oligomers in cell free and cell based assays, increases calcium and calcein recovery, and decreases markers of cell toxicity.


Based on these results, small-scale efficacy studies were conducted to evaluate the therapeutic potential of IIPP-1 in the Thy-1-ASYN transgenic animal model of PD (Rockenstein et al., 2002).  This transgenic mouse develops PD-like motor and non-motor deficits as well as neuropathological indices (including alpha-synuclein aggregates and decreases in synaptic markers) starting as early as 3 months of age.


In the present study, non-tg and tg THY1-ASYN male mice treated daily with 0, 1 or 5 mg/kg (IP) for 1 month, and then evaluated on measures of motor function.  Treatment with both 1 and 5 mg/kg IIPP-1 reversed motor deficits in transgenic mice, compared to vehicle treated transgenic mice.


Consistent with in vitro results, post mortem neuropathological examination of the CNS of these animals treated chronically with IIPP-1 demonstrated a decrease in alpha-synuclein aggregates and an increase in neuronal viability markers (MAP-2 & synaptophysin) in the CNS of transgenic mice compared to vehicle treated transgenic mice.  Taken together, these studies support the further careful evaluation of IIPP-1 as a putative disease modifying treatment for PD/DLB.