NICE, France — With a handful of symptomatic treatments but no disease-modifying therapies for Alzheimer's disease (AD) or Parkinson's disease (PD) yet available, future therapeutic advances may require taking a step back to move forward, using the latest molecular tools now available to reveal tPullhe underlying mechanisms of these diseases.
The 12th International Conference on Alzheimer's and Parkinson's Diseases and Related Neurological Disorders (AD/PD 2015) here presents some early clinical trials but largely focuses attention on the basic biology of these diseases. Medscape Medical News sat down with Abraham Fisher, PhD, president of AD/PD, to get his thoughts on how and where research should go to be able to find treatments that can truly modify the course of these diseases.
In Alzheimer's disease, he envisions a comprehensive approach that would reduce amyloid and phosphorylation of tau protein and neuroinflammation, as well as improve cognition, even though it's not clear at this point what the etiology of the disease really is. He sees a need for a multidimensional attack, whether with one drug that does it all or a "cocktail" of drugs each working by its own mechanism. He pointed out approaches being presented at the conference, most still in the preclinical stage.
"In Parkinson, I think we are in a better shape because we have already drugs," Dr Fisher noted. "However…we don't have yet a good disease modifier…so we still have a lot of things to do there, as well." Compared with drugs for AD, the PD drugs can relieve symptoms for a longer period.
Adding to the quest for more durable treatments, work is ongoing on imaging and diagnostics, mainly involving biomarkers, to make it easier, faster, and more uniform in evaluating treatment approaches. Furthermore, there has already been a 2-hour podium session on animal models, and even that was too short "because one of the problems with drug development is that you don't have good animal models that replicate not only the pathology of the disease but to a certain extent the etiology…what causes Alzheimer, what causes Parkinson," he said.
Need for Harmonization
Many animal models exist, but each presents a certain aspect of the disease, so there is no agreement on which is the best model as long as the causes of these diseases are unknown. Thus, the gathered experts have started a discussion to try to "harmonize" the models, discussing a more uniform approach and what is needed for good animal models of the diseases. Down the road, the ultimate proof of having chosen a good model will be candidate compounds that succeed in clinical trials.
Harmonization already exists to some extent for clinical trials in neurodegenerative diseases. "There are very clear rules about how to run a good clinical trial and what would be required for a drug that is supposed to be a symptomatic treatment, is supposed to be a disease modifier, or is supposed to be both," Dr Fisher said.
He pointed out that the exhibit hall is full of vendors showing their approaches to translational research, facilitating basic science leading to drug discovery. Many of them focus on biomarker development, assays for research, and providing research support with imaging, specialized tissue stains, testing candidate compounds in their own facilities, and data management.
Poster sessions have been a big draw here. In addition to scientific sessions running well into the evening, more than 400 posters are presented on each of 4 days. They range from the most basic science to early-stage clinical trials. Attendees have been shoulder-to-shoulder, with lots of interaction between observers and presenters (as well as a few minor collisions in the tightly packed aisles).
What New Drugs Should Offer
Dr Fisher shared his list of ideal criteria for any new drug. "A good drug has to be comprehensive… [and] reduce all of the pathologies that we are aware of in these diseases," he said.
He noted that several drug targets across diseases have already been identified, such a G protein–coupled receptors, sigma-1 receptors, ionic channels (eg, α-7 nicotinic acetylcholine receptors), M1 muscarinic receptors, anti-inflammatory agents, and β-secretase inhibitors to reduce amyloid aggregates). These approaches all use small molecules, in contrast to the monoclonal antibody approaches to reduce amyloid that have shown limited success, at best, in clinical trials for AD.
Because AD, PD, progressive supranuclear palsy, and other neurodegenerative diseases all involve protein aggregation, it may be possible for a single compound to work on a common mechanism that leads to aggregates, thereby possibly treating more than one condition with the same drug.
"I think that this is one of the scopes of this meeting — to try to bring together all the diseases under one umbrella," Dr. Fisher explained.
Dr. Fisher is on the scientific advisory board of Anavex.
12th International Conference on Alzheimer's and Parkinson's Diseases and Related Neurological Disorders (AD/PD 2015)
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Cite this: AD/PD: Neurodegeneration Meeting Explores New Approaches - Medscape - Mar 20, 2015.