News — NanoNewron, Inc., a startup founded based on technology developed at Rutgers, The State University of New Jersey, looks to advance its potentially game changing approach towards treating Alzheimer’s Disease and other neurological conditions.
professor of Pharmacology, Physiology & Neuroscience PhD, MD, the Herbert and Jacqueline Klein Endowed Chair in Alzheimer's Disease and Neurodegeneration Research at the and founder of , developed three technologies that he believes can work together to treat Alzheimer’s more effectively than current methods.
“Most of the Alzheimer’s therapeutics are focused on the pathology of the disease: Amyloid-b and tau, the proteins that cause amyloid plaques and neurofibrillary tangles, which are considered hallmarks of the disease,” said D’Adamio. “My idea was to target a different metabolic pathway to interfere with the disease process in order to impact the root causes of the pathology.”
D’Adamio focused on a protein produced by certain immune cells called Tumor Necrosis Factor alpha (TNF-α), which causes inflammation and is also believed to play a role in the synthesis of the plaques and tangles of AD. Through his research, D’Adamio believes that TNF-α itself plays a pathogenic role in AD due to its ability to control synaptic activity in the brain, the early dysfunction of which is “one of the main hallmarks of cognitive decline associated with Alzheimer’s,” according to the . To that end, the first technology D’Adamio developed is a nanobody that can inhibit the inflammatory and synaptic effects of TNF-α.
The next step was to determine a method to transport these nanobodies into the brain, as they would have to cross through the blood brain barrier – a natural protective membrane that protects the central nervous system (CNS) from toxins and pathogens in the blood. D’Adamio believes his second technology, the NewroBusTM, can solve this problem.
According to D’Adamio, NewroBusTM consists of nanobodies binding to the Transferrin Receptor one (TfR1), which is a type II transmembrane protein expressed by many cells that mediates the uptake of iron in the cells. TfR1 can allow passage through the blood brain barrier through a process called transcytosis, in which macromolecules (such as nanobodies) move through the interior of a cell from one end to the other. “We have demonstrated that NewroBusTM is a nanobody that can efficiently cross the blood brain barrier,” he said.
D’Adamio then combined the first two technologies to create the third: a molecule called NN-841, which pairs two TNF-α inhibitor nanobodies on either side of the NewroBusTM, itself a nanobody. “Our in vivo studies have demonstrated that NN-841 is able to pass through the blood brain barrier through the NewroBusTM’ ability to bind TfR1 and exploit its physiological transcytosis effect,” he stated. Through this process, D’Adamio believes the technology will be able to target TNF-α within the brain and inhibit the inflammation and synaptic alterations that could be the root causes of Alzheimer’s.
“NN-841 is a trimer, a molecule composted of three nanobodies molecules: two against the TNF-α and in the middle the NewroBusTM, which essentially carries the molecule across the blood brain barrier very efficiently,” said D’Adamio. “Currently there is not a specific biologic TNF-α inhibitor that can actually cross the BBB; our molecule is the first. So now we not only have a technology that can transport therapeutics into the CNS, we also have made our own CNS therapeutic.”
The next steps for the company include discussions with the FDA to get approval to use NN-841 in clinical trials on humans, and D’Adamio hopes to be approved for a phase 2 STTR grant from the NIH to help to advance NN841 to preclinical trials and other development activities that will also leverage the support of Rutgers.
“Although our primary focus is Alzheimer’s, I believe this technology could have a therapeutic benefit on many conditions that involve TNF-α, including traumatic brain injury, multiple sclerosis, Huntington’s Disease, Parkinson’s Disease, epilepsy, and even certain mood disorders,” said D’Adamio.
data shows that over 55 million suffer from AD and that number could grow as high as 139 million by 2050. According to the (NIH), almost seven million Americans above the age of 65 are living with the disease, and “that number could grow to 13.8 million by 2060, barring the development of medical breakthroughs to prevent or cure AD.”
“There is still a dire need for more effective treatments for Alzheimer’s Disease,” said Marco Taglietti, MD, CEO of NanoNewron. “Despite decades of research, the current treatments only offer temporary improvements in symptoms and just a modest slowdown of cognitive decline. Currently there is no treatment that blocks the underlying progression of cognitive deterioration in Alzheimer’s disease, let alone curing it. At NanoNewron, our mission is to leverage these technologies to change that.”
“Dr. Adamio’s innovations have the potential to make a positive impact for so many families around the world,” said Deborah Perez Fernandez, PhD, MBA, executive director of the Office for Research (OfR) Technology Transfer unit, which patented the technologies and executed the licensing agreement to NanoNewron.
Added Vince Smeraglia, JD, executive director of the OfR’s New Ventures department, “we are proud to have connected Dr. D’Adamio with Marco, and we know that together they are a formidable team that will hopefully lead to the advancement of NanoNewron’s patented inventions.”
RSS