Despite years of research, there are few treatment options available that address all the various cognitive, sensory and motor dysfunctions associated with neurodegenerative diseases. Consider that cholinesterase inhibitors reportedly help reduce agitation in people with Alzheimer’s disease, but they may have limited effects on improving memory, problem-solving and regulating their mood. Similarly, the popular Parkinson’s drug, L-DOPA, can reduce tremors but it does not address other motor deficits like gait and balance, but has limited effects on improving cognition. Most distressingly, there are no therapeutic agents to effectively slow the progression of these diseases.
Given the growing aging population and the immense burden of neurodegenerative diseases, now is the time for pharma and biotech companies to bring new treatments to the clinic.
“There is a huge unmet medical need for slowing down the degenerative process,” said Dr. Errol De Souza, President and CEO of Neuropore Therapies, in an interview with Xtalks. “The holy grail is to have treatment disease modifications. That’s where the huge opportunity is.”
Neuropore Therapies, an emerging biotech based in San Diego, works on the development of small molecule agents aimed at addressing multiple facets of neurodegenerative disease. The 10-year old company was spun out of University of California, San Diego and was originally established to develop animal models in these neurodegenerative diseases. Now, they have four development programs in their pipeline, each targeting a unique aspect of neurodegenerative disease.
This week, the company announced the launch of a Phase Ib clinical study for UCB0599, a compound which targets the misfolding and oligomerization of the neuronal protein alpha-synuclein, a process widely believed to be involved in the pathology of Parkinson’s disease. The safety study in Parkinson’s disease patients is being conducted by UCB Pharmaceuticals, the Belgian biopharma company with whom Neuropore Therapies announced a license agreement in 2015.
“[For a small biotech company like Neuropore], we need to find the right balance between developing these [research] programs to a certain stage and using partnering strategies like we have with UCB to be able to bring in the financial resources that it’s going to take [to advance clinical development],” said De Souza.
In addition to their licensed product UCB0599, the company also has built programs aimed at stimulating the removal of neurotoxic proteins from the central nervous system and for quenching the chronic neuroinflammation present in patients with neurodegenerative disorders.
Their most advanced anti-neuroinflammation program is NPT520-34. This compound is effective across animal models of Parkinson’s, ALS and Alzheimer’s at both reducing the markers of neuroinflammation and the accumulation of the neuropathic forms of disease-associated proteins. Their preliminary work suggests that the primary mechanism of this small molecule is to inhibit microglial activation (the key cell system mediating chronic inflammation in the brain) with consequent benefits on protein aggregation and, in the Parkinson’s disease model, protection of dopaminergic neurons and improvements of motor symptoms.
Why does the small molecule work for all three neurodegenerative diseases? It’s based on a common mechanism, explains De Souza.
“By blocking the neuroinflammatory cascade in the brain that underlies all of these disorders, we are having a much broader effect,” he said.
For NPT520-34, the team is conducting a Phase I trial with healthy volunteers and intends to start biomarker-based proof-mechanism studies by 2020.
A second program in the preclinical stage of development targeting neuroinflammation is the TLR2 antagonist program. TLR2 is a protein that is dysregulated in neurodegenerative diseases and contributes to the underlying disease pathology. Lead compounds from this program have been shown to have beneficial actions in neurons derived from Parkinson’s disease patients.
The company also has three other compounds at various stages of development which are designed to specifically increase the body’s ability to destroy the neurotoxic protein aggregates through autophagy. These programs are at an earlier stage of development but have the potential to complement the approaches taken with therapeutics that primarily target neuroinflammation.
Dr. De Souza praises the FDA and other regulatory agencies for implementing programs and pathways to accelerate clinical development in light of the high unmet medical need.
“When you think about the disease burden with the aging population, that really should not slow us down in terms of continuing to look for these [therapies],” he said.
Neuropore Therapies is just one of the biopharma companies investigating better treatment paradigms for not just Parkinson’s disease, but other neurodegenerative diseases as well.