NEW YORK – The path to great scientific discoveries is rarely a direct one – which makes the work of people like Nikolaos Tezapsidis, PhD, and Neurotez, Inc. the biotech company he founded in 2005 to pursue novel cures for dreaded Alzheimer’s, even more important.
Now that their research strongly suggests leptin helps, the priority is to raise funds – they are speaking with investment bankers and they are listed with poliwogg.com a crowd funding mechanism – so they can manufacture the protein and proceed to clinical trials.
Tezapsidis noted the consensus among researchers is that that plaques containing amyloid-beta or amyloid-beta itself are toxic and kill neurons, but they might be just signs or by-products of the disease.
“The story has evolved.” He remains “agnostic about whether the plaques or amyloid-beta are the culprit,” but he said “the idea that they do not cause the disease is gaining momentum.”
Some therapies that have seen clinical trials address their removal, “but none have proven efficacious in improving memory and cognition, “he said.
Tezapsidis said all that suggests they must look “upstream” for the culprit, prior to the formation of the plaques.
His firm’s hypothesis is similar to another idea scientists are exploring that Alzheimer’s is a Type 3 Diabetes disorder. “Something in the metabolism goes wrong, whether there is the inability of the brain to receive signals to use glucose, which neurons need for energy, communication problems, or abnormalities in lipids which form membranes, or whether there is a lack of metabolic factors, like the leptin that leave the process.”
Researchers know there is a high density of leptin receptors in the hippocampus, which is the brain center that controls memory and is primarily affected in the initial phases of the Alzheimer’s.
He was inspired by very good chemistry and physics teachers in Greece, and his business savvy comes from his parents, high school sweethearts from entrepreneurial families who immigrated to Australia from Greece.
Tezapsidis was born in Melbourne, but the family returned to Greece when he was eight. He attended high school in Argos Orestiko, near Kastoria and university in Thessaloniki and after studying chemistry in Greece, he earned a masters and PhD in biochemistry in England.
He was always interested in neuroendocrinology and neurochemistry. “I always had a desire to connect the brain with chemistry,” he said.
Coincidentally, spurred by a mentor, Dr. Nikolaos Robakis of Mt. Sinai, one of the Alzheimer’s pioneers, he turned his focus to brain-wasting illness in 1994, but the possible significance of metabolic pathways came in later, making Tezapsidis’ neuroendocrine expertise valuable.
Asked why there has been relatively little progress since the disease was identified in 1907, Tezapsidis said it was not because of a lack of effort.
Scientists simply did not have the technology to easily sequence genes that they now have at their disposal. “It was a painstaking and long process,” so the discoveries that were made were remarkable he said, noting “The first time we actually had a molecular basis for the disease was 1987 when they first isolated the gene sequence of the precursor of the peptide that is deposited in plaques.”
Regardless of whether amyloid beta is toxic, he says “it is important to understand how it is produced or cleared because this will give us clues as to why this is happening.”
“If we remove it early enough maybe there is a benefit, but if there is an underlying pathology either overproducing or failing to clear it, it will re-emerge, so you need to address the upstream molecular process that is causing it.“
Neurotez, based in Bridgewater, NJ, was founded in 2005. The work of the company was based upon research done at Columbia University, which was Tezapsidis’ last academic home.
They focused on the potential of leptin, but he was also involved in previous work on screening technologies, which led to patents.
His wife Jane Johnston Tezapsidis has a PhD in biology and is an intricate part of the company at VP of operations.
They have two daughters, Katie, who studies computer science at NYU, and Victoria, a high school senior.
His younger brother is an architect in Greece. Asked if his brother took his path because he was more visual, Tezapsidis said he was pretty visual himself, which is also valuable in his field.
Among those who would have benefitted from leptin being available was his mother. Because it was not FDA approved, they could not get access to it in time to help her.
“She was deficient in leptin to begin with, but it is also known to have cognitive benefit,” he said. It is believed leptin provides neurotrophic support – keeping neurons healthy – that would have corrected her memory problems,” he said.
Tezapsidis will manufacture his own in the hopes of helping future patients.
Leptin is a protein that humans make and the company is in the process of producing clinical grade material necessary for clinical trials.
“Proteins are more technologically demanding to produce than the smaller molecules that have been traditionally been produced by pharmaceutical companies,” he explained.
They need live cultures of cells to generate the protein, and the purification process critical.
The protein can be produced by bacteria or mammalian cells that can be genetically engineered and instructed to produce leptin.
Bacteria have plusses and minuses: they can be produced in massive amounts, but can become contaminated, and the extra care is expensive.
Mammalian cells are both more expensive to work with and take longer to produce.
Although Neurotez can switch to mammalian cells, its first trials will use bacterially produced proteins. “We are ready to move into the manufacturing suite, but we need the funds,” Tezapsidis told The National Herald.