Doctors and researchers have hit frustrating walls in understanding and treating Alzheimer’s Disease over the past few decades. But one small company in Pennsylvania may have made a significant breakthrough.
Dr. Alois Alzheimer discovered his namesake disease over 100 years ago after he noticed unusual changes in the brain tissue of a female patient who died with severe dementia. He described what we call plaques and tangles, leading to new approaches to remove the plaques and the tangles.
When Dr. Maria Maccecchini, the CEO and founder of Annovis Bio (NYSE:ANVS), was completing her Ph.D. in biochemistry in 1978 the “cholinergic hypothesis” was prevalent. It ascribed the memory loss and other symptoms associated with Alzheimer’s to a deficiency of the neurotransmitter acetylcholine, which is a chemical important to proper memory function. Medications to correct the acetylcholine deficiency were shown to improve attention slightly but had no effect on the progression of the disease.
In the late ’80s researchers discovered that amyloid protein was present in plaque in Down Syndrome and Alzheimer’s patients. By the ’90s researchers determined that mutations increasing the production of amyloid led to Alzheimer’s disease. The “amyloid hypothesis” became the prevailing theory of the cause of memory and personality destroying disease.
For the next 20 years removing the amyloid and plaque was the most favored approach to treating Alzheimer’s.
Over $40 billion has been spent to develop drugs to treat amyloid, resulting in over 500 failed clinical trials without developing a drug that slows the progression or reverses the effects of Alzheimer’s. This approach has failed.
A recent article in Scientific American sums up the problem:
“Finding drugs to treat dementia is especially difficult because the brain is relatively inaccessible and harder to test and deliver compounds to, explains Simon Lovestone, a professor of translational neuroscience at the University of Oxford, UK. Less is known about the biology of the condition than, say, cancer.”
A NEW APPROACH
Dr. Maria Maccecchini has over 65 patents, many of them focused on neurodegenerative diseases. Dr. Maccecchini’s career includes a PhD in biochemistry from the Biocenter of Basel and two post-doctoral degrees, one at the Roche-Institute of Immunology, and another at Caltech. She has worked for Bachem Bioscience, the U.S. subsidiary of Bachem AG, Switzerland and was head of Molecular Biology for Mallinckrodt. In 1992 she founded Symphony Pharmaceuticals, focused on protecting nerve cells from dying, and sold that company nine years later.
In May of 2008 she founded Annovis Bio to develop better therapeutics for Alzheimer’s, Parkinson’s, and other neurodegenerative diseases and to protect nerve cells from dying. She took the company public on the NYSE American in January 2020 at $6 per share, raising $14 million. She and her team take a new approach to treating Alzheimer’s disease.
“The drug industry invested a lot of time and money into the hypothesis that sticky brain plaque causes Alzheimer’s disease, but this idea has been proven wrong,” she Dr. Maccicchini says. “Lately we have seen that the tau hypothesis also does not improve memory and learning and does not slow the course of the disease, so we have pioneered a new approach.”
During her decades of research on neurodegenerative diseases she discovered that chronic and acute brain insults (injuries) lead to high levels of neurotoxic proteins and inflammation. In healthy nerve cells communication within nerve cells as well as with other nerve cells and body parts is carried by small packages containing neurotransmitters, nerve growth factors, and other important molecules. This is called axonal transport – the information highway of the nerve cell. For a nerve cell to be healthy, axonal transport needs to be unimpaired. High levels of neurotoxic proteins limit axonal transport, which causes a toxic cascade leading to nerve cell death, and the brain develops diseases such as Alzheimer’s.
Dr. Maccicchini developed ANVS401, the only drug to attack multiple neurotoxic proteins simultaneously. In a proof-of-concept study with mild cognitive-impaired patients, ANVS401 lowered the levels of APP/AB, tau/p-tau, and aSYN back to the levels of healthy volunteers.
Remarkably, the drug lowered the levels of three neurotoxic proteins known to cause Alzheimer’s and Parkinson’s. By doing so, the drug lowered inflammation and improved the information highway. Several animal studies have backed these findings.
A recent article published in the prestigious Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association further validated ANVS401 as the only drug to improve axonal transport.
Dr. William Mobley’s lab at the UCSD Department of Neurosciences published peer-reviewed data supporting the basic hypothesis of the efficacy of Annovis’ drug: that it lowered levels of neurotoxic proteins, normalized axonal transport, lowered inflammation, and led to normal mouse behavior.
Annovis is currently in two phase 2 Alzheimer’s and Parkinson’s clinical trials.
Annovis reported its first statistically significant interim data from these trials in March 2021, demonstrating ANVS401 improved patients’ speed and coordination scores in key Parkinson’s tests, with no adverse events. Annovis reported additional statistically significant positive Parkinson’s data in May when it demonstrated that ANVS401 significantly lowered the levels of inflammatory markers in Parkinson’s patients.
Days after reporting positive Parkinson’s data, Annovis announced ANVS401 improved cognition in Alzheimer’s patients with a statistically significant 3.3 improvement on the key ADAS-Cog11 test.
This positive interim data has drawn institutional investors to join in a $50 million capital raise at $50 per share in late May, providing the funds for Annovis to complete its current trials and launch a Phase 3 study in Alzheimer’s in persons with Down Syndrome.
This new approach could change forever the way the scientific community thinks about Alzheimer’s and Parkinson’s. Dr. Maccecchini’s novel idea for treating neurodegeneration could make all the difference in the world. Big things sometimes come from small places.
