The Alzheimer’s Drug Discovery Foundation is proud to have supported over 20% of all the treatments for Alzheimer’s now in clinical trials. One of the most innovative of these is ORY-2001, which is being developed by Oryzon Genomics.

Oryzon is a biopharmaceutical company founded in 2000 in Barcelona, Spain, that has emerged as a global leader in epigenetic therapies. Epigenetics is a new area for drug development. Rather than trying to change actual genes, epigenetic drugs change how, and how much, those genes are expressed.

Researchers have identified numerous genes involved in Alzheimer’s disease. With initial support from the ADDF in 2000, Dr. Tamara Maes and her team at Oryzon developed ORY-2001. It works by inhibiting a protein that “turns down” the expression of several genes that are beneficial to the brain. By helping these genes express more, ORY-2001 may slow cognitive impairment and restore memory deficits in patients with Alzheimer’s and other disorders. In fact, preclinical testing has shown that ORY-2001 also holds promise for patients with multiple sclerosis.

The ADDF funded Oryzon again in 2015 to help prepare for human clinical trials. ORY-2001 became the first epigenetic therapy for any neurodegenerative disease to make it to clinical trials last year when it initiated a phase 1 study in 40 volunteers. That trial successfully demonstrated the drug’s safety. Another phase 1 clinical trial is currently underway to determine its optimal dose. And phase 2 clinical trials are being planned for later this year.
The Alzheimer’s Drug Discovery Foundation (ADDF) is committed to advancing the best ideas to prevent and treat Alzheimer’s disease. As detailed in our Clinical Trials Report, 20% of the treatments for Alzheimer’s in clinical trials received support from us.

One of the most exciting of those treatments is allopregnanolone, which is being developed by Roberta Diaz Brinton, PhD. Dr. Brinton is the inaugural Director of the Center for Innovation in Brain Science at the University of Arizona, where she also serves as Professor of Pharmacology and Neurology in the College of Medicine - Tucson. Her research focuses on the bioenergetic and regenerative systems of the brain. 

Dr. Brinton’s discovered that allopregnanolone, a neuro-steroid, can activates neural stem cells to generate new brain cells. This process is called “neurogenesis” and it has the potential to restore lost cognitive function in Alzheimer's patients. Other researchers have attempted to spur neurogenesis directly using stem cells, but have failed. With support from the ADDF since 2004, Dr. Brinton developed allopregnanolone as a therapeutic that stimulates the proliferation of stem cells. In preclinical testing, this approach promoted neurogenesis and restored cognitive function.

Dr. Brinton has successfully completed a phase 1b/2a human clinical trial. She is now preparing for a larger phase 2 clinical trial, which is also receiving funding from the ADDF.
The Alzheimer’s Drug Discovery Foundation has supported over 20% of all the treatments for Alzheimer’s currently in clinical trials. One of the most promising of these is C-31 (also called LM11A-31), which was developed by Frank Longo, MD, PhD. Dr. Longo, a professor at the Stanford School of Medicine and founder of the biotechnology firm PharmatrophiX, received his first grant from the ADDF in 2000 for what was then just an idea. He thought that affecting the p75 receptor on the surface of neurons might keep those neurons alive and slow the progression of Alzheimer’s disease. With seed funding from the ADDF, he set out to find compounds to do just that.

And he succeeded. Sixteen years and six ADDF grants later, he’s testing the effectiveness of C-31 in phase 2 clinical trials in Alzheimer’s patients, which are expected to be completed in 2018. By affecting the p75 receptor, the drug counteracts abnormal signals in the brain. Dr. Longo explains, “When this abnormal signaling occurs, synaptic function begins to suffer and neurons begin to die and degenerate—at this stage, patients begin to suffer the memory loss and behavioral changes that are characteristic of Alzheimer’s.”

Thanks to the ADDF, Dr. Longo is moving closer to achieving his goal of curing Alzheimer’s disease. As a child, frustrated that doctors were unable to help his younger sister with cerebral palsy, he dreamed of becoming a physician who could fix diseases of the brain. He made it to medical school and ultimately found his niche in Alzheimer’s research and patient care. “I was always attracted to diseases that were not curable,” Dr. Longo says. “And Alzheimer’s is an area that’s ripe for significant advances. There are so many exciting opportunities for developing therapeutics.”

When Dr. Longo isn’t in the lab, he’s with the patients who inspire him to continue his work. “I feel such frustration at not being able to provide better treatments than what existed 15 years ago,” he says. “Seeing patients provides so much motivation to work hard on the research front.”
Funding from the Alzheimer’s Drug Discovery Foundation helps the best ideas to prevent and treat Alzheimer’s disease advance. Today, more than 20% of all treatments for Alzheimer’s currently in clinical trials received critical support from us. AGB101, a drug being developed by Dr. Michela Gallagher and Agenebio, has made it the furthest of any program in our portfolio.

Dr. Gallagher, who is also a professor at Johns Hopkins University, is preparing for a phase 3 trial of AGB101. The drug targets brain hyperactivity, which is involved in memory loss. Reducing this hyperactivity with AGB101 appears to restore memory. The upcoming trial will test the drug in patients with mild cognitive impairment, a pre-dementia condition in which memory is worse than expected for a person’s age. Because the drug is given at this early stage, it could potentially slow progression of mild cognitive impairment enough that it never progresses to Alzheimer’s disease. Dr. Gallagher is hopeful that, if results from the phase 3 trial are positive, AGB101 will be available to patients soon after.

This drug was developed with support from the Alzheimer’s Drug Discovery Foundation, which began in 2010. “I don’t know how we would have gotten started at AgeneBio without the ADDF,” Dr. Gallagher says. “It was the bridge to a program that is still doing very well, and we’re tremendously grateful to the Foundation for its continued support.”
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